The Role of Exercise in Prevention and Treatment of Osteopenia of Prematurity: An Update.

PubMed

Eliakim, Alon; Litmanovitz, Ita; Nemet, Dan

2017-11-01

Premature infants have an increased risk of osteopenia due to limited bone mass accretion in utero and a greater need for bone nutrients. Until recently, most efforts to prevent osteopenia of prematurity focused on nutritional changes. Recent studies indicate that passive range-of-motion exercise of the extremities may lead to beneficial effects on body weight, increased bone mineralization, increased bone formation markers and leptin levels, and attenuation of the natural postnatal decline in bone speed of sound. These results suggest that exercise may play an important role in the prevention and treatment of osteopenia of prematurity. This review summarizes our current knowledge on the role of exercise in the prevention and treatment of osteopenia of prematurity.

Bone mineralization in childhood and adolescence.

PubMed

Bachrach, L K

1993-08-01

Prevention of osteoporosis depends on establishing adequate peak bone mass in the first two decades of life. Achievement of this goal requires an understanding of factors that promote skeletal health. Genetic factors are important determinants of adult bone mass, but nonheritable variables, including body mass, calcium nutriture, sex steroids, and activity can strongly influence whether maximal bone mineral is achieved. Acquisition of bone mineral continues throughout childhood and adolescence, reaching a lifetime maximum in early adulthood. Adolescence is a particularly critical time for bone mineral accretion as more than half of the bone calcium is normally laid down during the teen years. Chronic illness, malnutrition, or endocrine deficiencies at this age may result in profound deficits in bone mass, which may not be fully reversible. These risk factors contribute to the osteopenia associated with anorexia nervosa, exercise-induced amenorrhea, delayed puberty, Turner's syndrome, and growth hormone deficiency.

Episodic accretion: the interplay of infall and disc instabilities

NASA Astrophysics Data System (ADS)

Kuffmeier, Michael; Frimann, Søren; Jensen, Sigurd S.; Haugbølle, Troels

2018-04-01

Using zoom-simulations carried out with the adaptive mesh-refinement code RAMSES with a dynamic range of up to 227 ≈ 1.34 × 108 we investigate the accretion profiles around six stars embedded in different environments inside a (40 pc)3 giant molecular cloud, the role of mass infall and disc instabilities on the accretion profile, and thus on the luminosity of the forming protostar. Our results show that the environment in which the protostar is embedded determines the overall accretion profile of the protostar. Infall on to the circumstellar disc may trigger gravitational disc instabilities in the disc at distances of around ˜10 to ˜50 au leading to rapid transport of angular momentum and strong accretion bursts. These bursts typically last for about ˜10 to a ˜100 yr, consistent with typical orbital times at the location of the instability, and enhance the luminosity of the protostar. Calculations with the stellar evolution code MESA show that the accretion bursts induce significant changes in the protostellar properties, such as the stellar temperature and radius. We apply the obtained protostellar properties to produce synthetic observables with RADMC3D and predict that accretion bursts lead to observable enhancements around 20 to 200 μm in the spectral energy distribution of Class 0 type young stellar objects.

Accretion rates of protoplanets 2: Gaussian distribution of planestesimal velocities

NASA Technical Reports Server (NTRS)

Greenzweig, Yuval; Lissauer, Jack J.

1991-01-01

The growth rate of a protoplanet embedded in a uniform surface density disk of planetesimals having a triaxial Gaussian velocity distribution was calculated. The longitudes of the aspses and nodes of the planetesimals are uniformly distributed, and the protoplanet is on a circular orbit. The accretion rate in the two body approximation is enhanced by a factor of approximately 3, compared to the case where all planetesimals have eccentricity and inclination equal to the root mean square (RMS) values of those variables in the Gaussian distribution disk. Numerical three body integrations show comparable enhancements, except when the RMS initial planetesimal eccentricities are extremely small. This enhancement in accretion rate should be incorporated by all models, analytical or numerical, which assume a single random velocity for all planetesimals, in lieu of a Gaussian distribution.

The temporal response of bone to unloading

NASA Technical Reports Server (NTRS)

Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

1984-01-01

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Accretion rates of protoplanets. II - Gaussian distributions of planetesimal velocities

NASA Technical Reports Server (NTRS)

Greenzweig, Yuval; Lissauer, Jack J.

1992-01-01

In the present growth-rate calculations for a protoplanet that is embedded in a disk of planetesimals with triaxial Gaussian velocity dispersion and uniform surface density, the protoplanet is on a circular orbit. The accretion rate in the two-body approximation is found to be enhanced by a factor of about 3 relative to the case where all planetesimals' eccentricities and inclinations are equal to the rms values of those disk variables having locally Gaussian velocity dispersion. This accretion-rate enhancement should be incorporated by all models that assume a single random velocity for all planetesimals in lieu of a Gaussian distribution.

How do accretion discs break?

NASA Astrophysics Data System (ADS)

Dogan, Suzan

2016-07-01

Accretion discs are common in binary systems, and they are often found to be misaligned with respect to the binary orbit. The gravitational torque from a companion induces nodal precession in misaligned disc orbits. In this study, we first calculate whether this precession is strong enough to overcome the internal disc torques communicating angular momentum. We compare the disc precession torque with the disc viscous torque to determine whether the disc should warp or break. For typical parameters precession wins: the disc breaks into distinct planes that precess effectively independently. To check our analytical findings, we perform 3D hydrodynamical numerical simulations using the PHANTOM smoothed particle hydrodynamics code, and confirm that disc breaking is widespread and enhances accretion on to the central object. For some inclinations, the disc goes through strong Kozai cycles. Disc breaking promotes markedly enhanced and variable accretion and potentially produces high-energy particles or radiation through shocks. This would have significant implications for all binary systems: e.g. accretion outbursts in X-ray binaries and fuelling supermassive black hole (SMBH) binaries. The behaviour we have discussed in this work is relevant to a variety of astrophysical systems, for example X-ray binaries, where the disc plane may be tilted by radiation warping, SMBH binaries, where accretion of misaligned gas can create effectively random inclinations and protostellar binaries, where a disc may be misaligned by a variety of effects such as binary capture/exchange, accretion after binary formation.

Influence of hard vs. soft ground surfaces on bone accretion in prepubertal footballers.

PubMed

Carmona, M Plaza-; Vicente-Rodriguez, G; Martín-García, M; Burillo, P; Felipe, J L; Mata, E; Casajús, J A; Gallardo, L; Ara, I

2014-01-01

Information regarding osteogenic effects of physical activity performed on different playing surfaces is scarce. A total of 42 children (9.2±0.2 years, Tanner stages I-II) participated in this study. 14 were playing on artificial turf soft ground (SG), 14 on a natural non-grass hard ground (HG) and 14 were assigned to the sedentary control group (C). Whole body and hip scans (dual energy X-ray absorptiometry), anthropometric variables (weight and height) and physical fitness (VO2max) were determined in all participants. Bone mineral content (BMC) values were higher in the SG group compared to the C group at the legs (209.75±5.11 g vs. 187.42±5.14 g, respectively), pelvis (122.72±4.27 g vs. 98.58±4.29 g respectively) and whole-body level (1 126.1±22.81 g vs. 1 035.34±22.92 g, respectively). The hard ground (HG) group also showed higher values in the majority of BMC variables compared to the C group. Additionally, bone mineral density (BMD) was significantly higher at all sites of the hip in both active groups compared to control (P<0.05). No differences between HG and SG were found. In summary, similar bone mass accretion is obtained by prepubescent footballers independently of the surface on which they practice football. © Georg Thieme Verlag KG Stuttgart · New York.

Vitamin D supplementation in breastfed infants from Montréal, Canada: 25-hydroxyvitamin D and bone health effects from a follow-up study at 3 years of age.

PubMed

Gallo, S; Hazell, T; Vanstone, C A; Agellon, S; Jones, G; L'Abbé, M; Rodd, C; Weiler, H A

2016-08-01

Whether infant vitamin D supplementation may have long-term bone benefits is unclear. In this study, breastfed infants who received vitamin dosages greater than 400 IU/day did not have higher bone mineralization at 3 years. This study provides important data to inform pediatric public health recommendations for vitamin D. North American health agencies recommend breastfed infants should be supplemented with 400 IU of vitamin D/day to support bone health. Few studies examined the long-term benefits of early life vitamin D supplementation on bone mineralization. The objective of this study was to determine if a dose-response relationship exists between infant vitamin D supplementation, vitamin D status, and bone outcomes at 3 years of age. This was a double-blind randomized trial of 132, 1-month-old healthy, breastfed infants from Montréal, Canada, between 2007 and 2010. In this longitudinal analysis, 87 infants (66 %) returned for follow-up at 3 years of age, between 2010 and 2013. At 1 month of age, participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400, 800, 1200, or 1600 IU/day until 12 months of age. Lumbar spine vertebrae 1-4 (LS) bone mineral density (BMD), LS and whole body bone mineral content (BMC), and mineral accretion were measured by dual-energy x-ray absorptiometry at 3 years. At follow-up, the treatment groups were similar in terms of diet, sun exposure, and demographics. There were no significant differences among the groups in LS or whole body BMC, BMD, or accretion. Although, 25(OH)D concentrations were not different among the groups, higher doses (1200 and 1600 IU/day) achieved higher 25(OH)D area under the curve from 1 to 36 months vs. 400 IU/day. This is the first longitudinal follow-up of an infant vitamin D dose-response study which examines bone mineralization at 3 years of age. Dosages higher than 400 IU/day do not appear to provide additional benefits to the bone at follow-up. Larger studies with more ethnically diverse groups are needed to confirm these results.

Box-modeling of bone and tooth phosphate oxygen isotope compositions as a function of environmental and physiological parameters.

PubMed

Langlois, C; Simon, L; Lécuyer, Ch

2003-12-01

A time-dependent box model is developed to calculate oxygen isotope compositions of bone phosphate as a function of environmental and physiological parameters. Input and output oxygen fluxes related to body water and bone reservoirs are scaled to the body mass. The oxygen fluxes are evaluated by stoichiometric scaling to the calcium accretion and resorption rates, assuming a pure hydroxylapatite composition for the bone and tooth mineral. The model shows how the diet composition, body mass, ambient relative humidity and temperature may control the oxygen isotope composition of bone phosphate. The model also computes how bones and teeth record short-term variations in relative humidity, air temperature and delta18O of drinking water, depending on body mass. The documented diversity of oxygen isotope fractionation equations for vertebrates is accounted for by our model when for each specimen the physiological and diet parameters are adjusted in the living range of environmental conditions.

Osteoporosis: Modern Paradigms for Last Century's Bones.

PubMed

Kruger, Marlena C; Wolber, Frances M

2016-06-17

The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

Stochastic events lead to accretion in Saturn’s rings

NASA Astrophysics Data System (ADS)

Esposito, L. W.

2009-12-01

UVIS occultations indicate accretion is triggered at the B ring edge, in strong density waves in ring A and in the F ring. Moons may trigger accretion by streamline crowding (Lewis & Stewart); which enhances collisions, leading to accretion; increasing random velocities; leading to more collisions and more accretion. Cassini occultations of these strongly perturbed locations show not only accretion but also disaggregation, with time scales of hours to weeks. The collisions may lead to temporary aggregations via stochastic events: they can compress unconsolidated objects, trigger adhesion or bring small pieces into contact with larger or higher-density seeds. Disaggregation then can follow from disruptive collisions or tidal shedding. In the accretion/disruption balance, increased random motions could eventually give the upper hand to disruption… just as ‘irrational exuberance’ can lead to financial panic in the economy; or the overpopulation of hares can lead to boom-and-bust in the population of foxes. This unstable equilibrium can similarly give rise to episodic cycles in accretion: explaining why the observable ring features that indicate embedded objects have been increasing since the beginning of Cassini’s observations of Saturn in 2004.

Stochastic events lead to accretion in Saturn's rings

NASA Astrophysics Data System (ADS)

Esposito, Larry W.

2010-05-01

UVIS occultations indicate accretion is triggered at the B ring edge, in strong density waves in ring A and in the F ring. Moons may trigger accretion by streamline crowding (Lewis & Stewart); which enhances collisions, leading to accretion; increasing random velocities; leading to more collisions and more accretion. Cassini occultations of these strongly perturbed locations show not only accretion but also disaggregation, with time scales of hours to weeks. The collisions may lead to temporary aggregations via stochastic events: collisions can compress unconsolidated objects, trigger adhesion or bring small pieces into contact with larger or higher-density seeds. Disaggregation then can follow from disruptive collisions or tidal shedding. In the accretion/disruption balance, increased random motions could eventually give the upper hand to disruption… just as ‘irrational exuberance' can lead to financial panic in the economy; or the overpopulation of hares can lead to boom-and-bust in the population of foxes. This unstable equilibrium can similarly give rise to episodic cycles in accretion: explaining why the observable ring features that indicate embedded objects have been increasing since the beginning of Cassini's observations of Saturn in 2004.

Effects of Planetesimal Accretion on the Structural Evolution of Sub-Neptunes

NASA Astrophysics Data System (ADS)

Chatterjee, Sourav; Chen, Howard

2018-01-01

A remarkable discovery of NASA's Kepler mission is the wide diversity in the average densities of planets even when they are of similar mass. After gas disk dissipation, fully formed planets could accrete nearby planetesimals from a remnant planetesimal disk. We present calculations using the open-source stellar evolution toolkit Modules for Experiments in Stellar Astrophysics (MESA) modified to include the deposition of planetesimals into the H/He envelopes of sub-Neptunes. We show that planetesimal accretion can alter the mass-radius isochrones for these planets. The additional energy deposited via planetesimal accretion puffs up the envelopes leading to enhanced gas loss during the phase of rapid accretion. As a result, the same initial planet can evolve to contain very different final envelope-mass fractions. This manifest as differences in the average planet densities long after accretion stops. Differences in the accretion history, total accreted mass, and the inherent stochasticity of the accretion process can bring wide diversity in final average densities even when the initial planets are very similar. These effects are particularly important for planets initially less massive than ~10 MEarth and with envelope mass fraction less than ~10%, thought to be the most common type of planets discovered by Kepler.

Osteoporosis: Modern Paradigms for Last Century’s Bones †

PubMed Central

Kruger, Marlena C.; Wolber, Frances M.

2016-01-01

The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

Pulsed Accretion in the T Tauri Binary TWA 3A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tofflemire, Benjamin M.; Mathieu, Robert D.; Herczeg, Gregory J.

TWA 3A is the most recent addition to a small group of young binary systems that both actively accrete from a circumbinary disk and have spectroscopic orbital solutions. As such, it provides a unique opportunity to test binary accretion theory in a well-constrained setting. To examine TWA 3A’s time-variable accretion behavior, we have conducted a two-year, optical photometric monitoring campaign, obtaining dense orbital phase coverage (∼20 observations per orbit) for ∼15 orbital periods. From U -band measurements we derive the time-dependent binary mass accretion rate, finding bursts of accretion near each periastron passage. On average, these enhanced accretion events evolvemore » over orbital phases 0.85 to 1.05, reaching their peak at periastron. The specific accretion rate increases above the quiescent value by a factor of ∼4 on average but the peak can be as high as an order of magnitude in a given orbit. The phase dependence and amplitude of TWA 3A accretion is in good agreement with numerical simulations of binary accretion with similar orbital parameters. In these simulations, periastron accretion bursts are fueled by periodic streams of material from the circumbinary disk that are driven by the binary orbit. We find that TWA 3A’s average accretion behavior is remarkably similar to DQ Tau, another T Tauri binary with similar orbital parameters, but with significantly less variability from orbit to orbit. This is only the second clear case of orbital-phase-dependent accretion in a T Tauri binary.« less

Net Reaction Rate and Neutrino Cooling Rate for the Urca Process in Departure from Chemical Equilibrium in the Crust of Fast-accreting Neutron Stars

NASA Astrophysics Data System (ADS)

Wang, Wei-Hua; Huang, Xi; Zheng, Xiao-Ping

We discuss the effect of compression on Urca shells in the ocean and crust of accreting neutron stars, especially in superbursting sources. We find that Urca shells may be deviated from chemical equilibrium in neutron stars which accrete at several tenths of the local Eddington accretion rate. The deviation depends on the energy threshold of the parent and daughter nuclei, the transition strength, the temperature, and the local accretion rate. In a typical crust model of accreting neutron stars, the chemical departures range from a few tenths of kBT to tens of kBT for various Urca pairs. If the Urca shell can exist in crusts of accreting neutron stars, compression may enhance the net neutrino cooling rate by a factor of about 1-2 relative to the neutrino emissivity in chemical equilibrium. For some cases, such as Urca pairs with small energy thresholds and/or weak transition strength, the large chemical departure may result in net heating rather than cooling, although the released heat can be small. Strong Urca pairs in the deep crust are hard to be deviated even in neutron stars accreting at the local Eddington accretion rate.

An X-ray outburst from the rapidly accreting young star that illuminates McNeil's nebula.

PubMed

Kastner, J H; Richmond, M; Grosso, N; Weintraub, D A; Simon, T; Frank, A; Hamaguchi, K; Ozawa, H; Henden, A

2004-07-22

Young, low-mass stars are luminous X-ray sources whose powerful X-ray flares may exert a profound influence over the process of planet formation. The origin of the X-ray emission is uncertain. Although many (or perhaps most) recently formed, low-mass stars emit X-rays as a consequence of solar-like coronal activity, it has also been suggested that X-ray emission may be a direct result of mass accretion onto the forming star. Here we report X-ray imaging spectroscopy observations which reveal a factor approximately 50 increase in the X-ray flux from a young star that is at present undergoing a spectacular optical/infrared outburst (this star illuminates McNeil's nebula). The outburst seems to be due to the sudden onset of a phase of rapid accretion. The coincidence of a surge in X-ray brightness with the optical/infrared eruption demonstrates that strongly enhanced high-energy emission from young stars can occur as a consequence of high accretion rates. We suggest that such accretion-enhanced X-ray emission from erupting young stars may be short-lived, because intense star-disk magnetospheric interactions are quenched rapidly by the subsequent flood of new material onto the star.

The influence of anthropometry and body composition on children's bone health: the childhood health, activity and motor performance school (the CHAMPS) study, Denmark.

PubMed

Heidemann, Malene; Holst, René; Schou, Anders J; Klakk, Heidi; Husby, Steffen; Wedderkopp, Niels; Mølgaard, Christian

2015-02-01

Overweight, physical inactivity and sedentary behaviour have become increasing problems during the past decade. Increased sedentary behaviour may change the body composition (BC) by increasing the fat mass relative to the lean mass (LM). These changes may influence bone health to describe how anthropometry and BC predict the development of the bone accruement. The longitudinal study is a part of The CHAMPS study-DK. Children were DXA scanned at baseline and at 2-year follow-up. BC (LM, BF %) and BMC, BMD and BA were measured. The relationship between bone traits, anthropometry and BC was analysed by multilevel regression analyses. Of the invited children, 742/800 (93%) accepted to participate. Of these, 682/742 (92%) participated at follow-up. Mean (range) of age at baseline was 9.5 years (7.7-12.1). Height, BMI, LM and BF % predicted bone mineral accrual and bone size positively and independently. Height and BMI are both positive predictors of bone accruement. LM is a more precise predictor of bone traits than BF % in both genders. The effects of height and BMI and LM on bone accruement are nearly identical in the two genders, while changes in BF % have different but positive effects on bone accretion in both boys and girls.

A 2.5-dimensional viscous, resistive, advective magnetized accretion-outflow coupling in black hole systems: a higher order polynomial approximation

NASA Astrophysics Data System (ADS)

Ghosh, Shubhrangshu

2017-09-01

The correlated and coupled dynamics of accretion and outflow around black holes (BHs) are essentially governed by the fundamental laws of conservation as outflow extracts matter, momentum and energy from the accretion region. Here we analyze a robust form of 2.5-dimensional viscous, resistive, advective magnetized accretion-outflow coupling in BH systems. We solve the complete set of coupled MHD conservation equations self-consistently, through invoking a generalized polynomial expansion in two dimensions. We perform a critical analysis of the accretion-outflow region and provide a complete quasi-analytical family of solutions for advective flows. We obtain the physically plausible outflow solutions at high turbulent viscosity parameter α (≳ 0.3), and at a reduced scale-height, as magnetic stresses compress or squeeze the flow region. We found that the value of the large-scale poloidal magnetic field B P is enhanced with the increase of the geometrical thickness of the accretion flow. On the other hand, differential magnetic torque (-{r}2{\\bar{B}}\\varphi {\\bar{B}}z) increases with the increase in \\dot{M}. {\\bar{B}}{{P}}, -{r}2{\\bar{B}}\\varphi {\\bar{B}}z as well as the plasma beta β P get strongly augmented with the increase in the value of α, enhancing the transport of vertical flux outwards. Our solutions indicate that magnetocentrifugal acceleration plausibly plays a dominant role in effusing out plasma from the radial accretion flow in a moderately advective paradigm which is more centrifugally dominated. However in a strongly advective paradigm it is likely that the thermal pressure gradient would play a more contributory role in the vertical transport of plasma.

Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D.

PubMed

Tse, Sze Man; Kelly, H William; Litonjua, Augusto A; Van Natta, Mark L; Weiss, Scott T; Tantisira, Kelan G

2012-07-01

The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD). We sought to determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time. Children aged 5 to 12 years with mild-to-moderate asthma who participated in the Childhood Asthma Management Program were followed for a mean of 4.3 years. Total doses of inhaled corticosteroids and oral corticosteroids (OCSs) were recorded, serum 25-hydroxyvitamin D3 levels were measured at the beginning of the trial, and serial dual-energy x-ray absorptiometry scans of the lumbar spine were performed. Annual BMA rates were defined as follows: [(BMD at 4 years' follow-up - BMD at baseline)/4 years]. BMA was calculated for 780 subjects. In boys baseline vitamin D levels significantly modified the relationship between OCSs and BMA (vitamin D × OCS interaction, P= .023). Stratification by vitamin D levels showed a decrease in BMA with increased use of OCSs in vitamin D-insufficient boys only (P< .001). Compared with vitamin D-sufficient boys, vitamin D-insufficient boys exposed to more than 2 courses of OCSs per year had twice the decrease in BMA rate (relative to boys who were OCS unexposed). Vitamin D levels significantly modified the effect of OCSs on BMA in boys. Further research is needed to examine whether vitamin D supplementation in children with poorly controlled asthma might confer benefits to bone health. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Spectral Analysis and Experimental Modeling of Ice Accretion Roughness

NASA Technical Reports Server (NTRS)

Orr, D. J.; Breuer, K. S.; Torres, B. E.; Hansman, R. J., Jr.

1996-01-01

A self-consistent scheme for relating wind tunnel ice accretion roughness to the resulting enhancement of heat transfer is described. First, a spectral technique of quantitative analysis of early ice roughness images is reviewed. The image processing scheme uses a spectral estimation technique (SET) which extracts physically descriptive parameters by comparing scan lines from the experimentally-obtained accretion images to a prescribed test function. Analysis using this technique for both streamwise and spanwise directions of data from the NASA Lewis Icing Research Tunnel (IRT) are presented. An experimental technique is then presented for constructing physical roughness models suitable for wind tunnel testing that match the SET parameters extracted from the IRT images. The icing castings and modeled roughness are tested for enhancement of boundary layer heat transfer using infrared techniques in a "dry" wind tunnel.

Insulin-Like Growth Factor Regulates Peak Bone Mineral Density in Mice by Both Growth Hormone-Dependent and -Independent Mechanisms

PubMed Central

Mohan, Subburaman; Richman, Charmaine; Guo, Rongqing; Amaar, Yousef; Donahue, Leah Rea; Wergedal, Jon; Baylink, David J.

2010-01-01

To evaluate the relative contribution of the GH/IGF axis to the development of peak bone mineral density (BMD), we measured skeletal changes in IGF-I knockout (KO), IGF-II KO, and GH-deficient lit/lit mice and their corresponding control mice at d 23 (prepubertal), 31 (pubertal), and 56 (postpubertal) in the entire femur by dual energy x-ray absorptiometry and in the mid-diaphysis by peripheral quantitative computed tomography. Lack of growth factors resulted in different degrees of failure of skeletal growth depending on the growth period and the growth factor involved. At d 23, femoral length, size, and BMD were reduced by 25–40%, 15–17%, and 8–10%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. During puberty, BMD increased by 40% in control mice and by 15% in IGF-II KO and GH-deficient mice, whereas it did not increase in the IGF-I KO mice. Disruption of IGF-I, but not IGF-II, completely prevented the periosteal expansion that occurs during puberty, whereas it was reduced by 50% in GH-deficient mice. At d 56, femoral length, size, and BMD were reduced by 40–55%, 11–18%, and 25–32%, respectively, in mice deficient in IGF-I, IGF-II, and GH compared with the control mice. Our data demonstrate that: 1) mice deficient in IGF-I exhibit a greater impairment in bone accretion than mice deficient in IGF-II or GH; 2) GH/IGF-I, but not IGF-II, is critical for puberty-induced bone growth; and 3) IGF-I effects on bone accretion during prepuberty are mediated predominantly via mechanisms independent of GH, whereas during puberty they are mediated via both GH-dependent and GH-independent mechanisms. PMID:12586770

Young adolescents who respond to an inulin-type fructan substantially increase total absorbed calcium and daily calcium accretion to the skeleton

USDA-ARS?s Scientific Manuscript database

Calcium absorption and whole-body bone mineral content are greater in young adolescents who receive 8 g/d of Synergy, a mixture of inulin-type fructans (ITF), compared with those who received a maltodextrin control. Not all adolescents responded to this intervention, however. We evaluated 32 respond...

Structure and growth pattern of the bizarre hemispheric prominence on the rostrum of the fossil beaked whale Globicetus hiberus (Mammalia, Cetacea, Ziphiidae).

PubMed

Dumont, Maïtena; de Buffrénil, Vivian; Miján, Ismael; Lambert, Olivier

2016-10-01

The rostrum of most ziphiids (beaked whales) displays bizarre swollen regions, accompanied with extreme hypermineralisation and an alteration of the collagenous mesh of the bone. The functional significance of this specialization remains obscure. With the voluminous and dense hemispheric excrescence protruding from the premaxillae, the recently described fossil ziphiid Globicetus hiberus is the most spectacular case. This study describes the histological structure and interprets the growth pattern of this unique feature. Histologically, the prominence in Globicetus is made up of an atypical fibro-lamellar complex displaying an irregular laminar organization and extreme compactness (osteosclerosis). Its development is suggested to have resulted from a protraction of periosteal accretion over the premaxillae, long after the end of somatic growth. Complex shifts in the geometry of this tissue are likely to have occurred during its accretion and no indication of Haversian remodeling could be found. X-ray diffraction and Raman spectroscopy indicate that the bone matrix in the premaxillary prominence of Globicetus closely resembles that of the rostrum of the extant beaked whale Mesoplodon densirostris: apatite crystals are of common size and strongly oriented, but the collagenous meshwork within bone matrix seems to be extremely sparse. These morphological and structural data are discussed in the light of functional interpretations proposed for the highly unusual and diverse ziphiid rostrum. J. Morphol. 277:1292-1308, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Convection Enhances Magnetic Turbulence in AM CVn Accretion Disks

NASA Astrophysics Data System (ADS)

Coleman, Matthew S. B.; Blaes, Omer; Hirose, Shigenobu; Hauschildt, Peter H.

2018-04-01

We present the results of local, vertically stratified, radiation magnetohydrodynamic shearing-box simulations of magnetorotational instability (MRI) turbulence for a (hydrogen poor) composition applicable to accretion disks in AM CVn type systems. Many of these accreting white dwarf systems are helium analogs of dwarf novae (DNe). We utilize frequency-integrated opacity and equation-of-state tables appropriate for this regime to accurately portray the relevant thermodynamics. We find bistability of thermal equilibria in the effective-temperature, surface-mass-density plane typically associated with disk instabilities. Along this equilibrium curve (i.e., the S-curve), we find that the stress to thermal pressure ratio α varied with peak values of ∼0.15 near the tip of the upper branch. Similar to DNe, we found enhancement of α near the tip of the upper branch caused by convection; this increase in α occurred despite our choice of zero net vertical magnetic flux. Two notable differences we find between DN and AM CVn accretion disk simulations are that AM CVn disks are capable of exhibiting persistent convection in outburst, and ideal MHD is valid throughout quiescence for AM CVns. In contrast, DNe simulations only show intermittent convection, and nonideal MHD effects are likely important in quiescence. By combining our previous work with these new results, we also find that convective enhancement of the MRI is anticorrelated with mean molecular weight.

Truncated disks - advective tori solutions around BHs. I. The effects of conduction and enhanced Coulomb coupling

NASA Astrophysics Data System (ADS)

Hujeirat, A.; Camenzind, M.

2000-10-01

We present the first 2D quasi-stationary radiative hydrodynamical calculations of accretion flows onto BHs taking into account cooling via Bremsstrahlung, Compton, Synchrotron and conduction. The effect of enhanced Coulomb coupling is investigated also. Based on the numerical results obtained, we find that two-temperature (2T) accretion flows are best suited to describe hard states, and one-temperature (1T) in the soft states, with transition possibly depending on the accretion rate. In the 2T case, the ion-conduction enlarges the disk-truncation-radius from 5 to 9 Schwarzschild radii (RS). The ion-pressure powers outflows, hence substantially decreasing the accretion rate with decreasing radius. The spectrum is partially modified BB with hard photons emitted from the inner region and showing a cutoff at 100 keV. In the 1T case, conduction decreases the truncation radius from 7 to 5 RS and lowers the maximum gas temperature. The outflows are weaker, the spectrum is pre-dominantly modified BB and the emitted photons from the inner region are much harder (up to 175 keV). In both cases, the unsaturated Comptonization region coincides with the transition region between the disk and the advective torus. When gradually enhancing the Coulomb coupling, we find that the ion-temperature Ti decreases and the electron temperature Te increases, asymptotically converging to 1T flows. However, once the dissipated energy goes into heating the ions, ion-electron thermal decoupling is inevitable within the last stable orbit (RMS) even when the Coulomb interaction is enhanced by an additional two orders of magnitude.

Increases to Inferred Rates of Planetesimal Accretion due to Thermohaline Mixing in Metal-accreting White Dwarfs

NASA Astrophysics Data System (ADS)

Bauer, Evan B.; Bildsten, Lars

2018-06-01

Many isolated, old white dwarfs (WDs) show surprising evidence of metals in their photospheres. Given that the timescale for gravitational sedimentation is astronomically short, this is taken as evidence for ongoing accretion, likely of tidally disrupted planetesimals. The rate of such accretion, {\\dot{M}}acc}, is important to constrain, and most modeling of this process relies on assuming an equilibrium between diffusive sedimentation and metal accretion supplied to the WD’s surface convective envelope. Building on the earlier work of Deal and collaborators, we show that high {\\dot{M}}acc} models with only diffusive sedimentation are unstable to thermohaline mixing and that models that account for the enhanced mixing from the active thermohaline instability require larger accretion rates, sometimes reaching {\\dot{M}}acc}≈ {10}13 {{g}} {{{s}}}-1 to explain observed calcium abundances. We present results from a grid of MESA models that include both diffusion and thermohaline mixing. These results demonstrate that both mechanisms are essential for understanding metal pollution across the range of polluted WDs with hydrogen atmospheres. Another consequence of active thermohaline mixing is that the observed metal abundance ratios are identical to accreted material.

The calculation of annual limits of intake for plutonium-239 in man using a bone model which allows for plutonium burial and recycling.

PubMed

Priest, N D; Hunt, B W

1979-05-01

Values of the annual limit of intake (ALI) for plutonium-239 in man have been calculated using committed dose equivalent limits as recommended by ICRP in Publication 26. The calculations were made using a multicompartment bone model which allows for plutonium burial and recycling in the skeleton. In one skeletal compartment, the growing surfaces of cortical bone, it is assumed that plutonium deposits are retained and are not subject to resorption or recycling. In the trabecular bone compartment plutonium is taken to be resorbed with either subsequent redeposition onto bone surfaces or retention in the bone marrow. ALIs for plutonium-239 have been calculated assuming a range of rates of bone accretion (0-32 micron yr-1), different amounts of plutonium retained in the marrow (0-60%) and a 20%, 45% or 70% deposition of plutonium in the skeleton from the blood. The calculations made using this bone model suggest that 750 Bq (20 nCi) is an appropriate ALI for the inhalation of class W and class Y plutonium compounds and that 830 kBq and 5 MBq (23 muCi and 136 muCi) are the appropriate ALIs for the ingestion of soluble and insoluble forms of plutonium respectively.

Possible formation pathways for the low-density Neptune-mass planet HAT-P-26b

NASA Astrophysics Data System (ADS)

Ali-Dib, Mohamad; Lakhlani, Gunjan

2018-01-01

We investigate possible pathways for the formation of the low-density Neptune-mass planet HAT-P-26b. We use two different formation models based on pebble and planetesimal accretion, and includes gas accretion, disc migration and simple photoevaporation. The models track the atmospheric oxygen abundance, in addition to the orbital period, and mass of the forming planets, which we compare to HAT-P-26b. We find that pebble accretion can explain this planet more naturally than planetesimal accretion that fails completely unless we artificially enhance the disc metallicity significantly. Pebble accretion models can reproduce HAT-P-26b with either a high initial core mass and low amount of envelope enrichment through core erosion or pebbles dissolution, or the opposite, with both scenarios being possible. Assuming a low envelope enrichment factor as expected from convection theory and comparable to the values we can infer from the D/H measurements in Uranus and Neptune, our most probable formation pathway for HAT-P-26b is through pebble accretion starting around 10 au early in the disc's lifetime.

AR Sco as a possible seed of highly magnetized white dwarf

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Banibrata; Rao, A. R.; Bhatia, Tanayveer Singh

2017-12-01

We explore the possibility that the recently discovered white dwarf pulsar AR Sco acquired its high spin and magnetic field due to repeated episodes of accretion and spin-down. An accreting white dwarf can lead to a larger mass and consequently a smaller radius thus causing an enhanced rotation period and a magnetic field. This spinning magnetic white dwarf temporarily can inhibit accretion, spin down and eventually, the accretion can start again due to the shrinking of the binary period by gravitational radiation. A repetition of the above cycle can eventually lead to a high magnetic field white dwarf, recently postulated to be the reason for overluminous type Ia supernovae. We also point out that these high magnetic field spinning white dwarfs are attractive sites for gravitational radiation.

RADIO IMAGING OBSERVATIONS OF PSR J1023+0038 IN AN LMXB STATE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deller, A. T.; Moldon, J.; Patruno, A.

2015-08-10

The transitional millisecond pulsar (MSP) binary system PSR J1023+0038 re-entered an accreting state in 2013 June in which it bears many similarities to low-mass X-ray binaries (LMXBs) in quiescence or near-quiescence. At a distance of just 1.37 kpc, PSR J1023+0038 offers an unsurpassed ability to study low-level accretion onto a highly magnetized compact object. We have monitored PSR J1023+0038 intensively using radio imaging with the Karl G. Jansky Very Large Array, the European VLBI Network and the Low Frequency Array, seeing rapidly variable, flat spectrum emission that persists over a period of six months. The flat spectrum and variability aremore » indicative of synchrotron emission originating in an outflow from the system, most likely in the form of a compact, partially self-absorbed jet, as is seen in LMXBs at higher accretion rates. The radio brightness, however, greatly exceeds extrapolations made from observations of more vigorously accreting neutron star LMXB systems. We postulate that PSR J1023+0038 is undergoing radiatively inefficient “propeller-mode” accretion, with the jet carrying away a dominant fraction of the liberated accretion luminosity. We confirm that the enhanced γ-ray emission seen in PSR J1023+0038 since it re-entered an accreting state has been maintained; the increased γ-ray emission in this state can also potentially be associated with propeller-mode accretion. Similar accretion modes can be invoked to explain the radio and X-ray properties of the other two known transitional MSP systems XSS J12270–4859 and PSR J1824–2452I (M28I), suggesting that radiatively inefficient accretion may be a ubiquitous phenomenon among (at least one class of) neutron star binaries at low accretion rates.« less

Simulations of small solid accretion on to planetesimals in the presence of gas

NASA Astrophysics Data System (ADS)

Hughes, A. G.; Boley, A. C.

2017-12-01

The growth and migration of planetesimals in a young protoplanetary disc are fundamental to planet formation. In all models of early growth, there are several processes that can inhibit grains from reaching larger sizes. Nevertheless, observations suggest that growth of planetesimals must be rapid. If a small number of 100 km sized planetesimals do manage to form in the disc, then gas drag effects could enable them to efficiently accrete small solids from beyond their gravitationally focused cross-section. This gas-drag-enhanced accretion can allow planetesimals to grow at rapid rates, in principle. We present self-consistent hydrodynamics simulations with direct particle integration and gas-drag coupling to estimate the rate of planetesimal growth due to pebble accretion. Wind tunnel simulations are used to explore a range of particle sizes and disc conditions. We also explore analytic estimates of planetesimal growth and numerically integrate planetesimal drift due to the accretion of small solids. Our results show that, for almost every case that we consider, there is a clearly preferred particle size for accretion that depends on the properties of the accreting planetesimal and the local disc conditions. For solids much smaller than the preferred particle size, accretion rates are significantly reduced as the particles are entrained in the gas and flow around the planetesimal. Solids much larger than the preferred size accrete at rates consistent with gravitational focusing. Our analytic estimates for pebble accretion highlight the time-scales that are needed for the growth of large objects under different disc conditions and initial planetesimal sizes.

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging.

PubMed

Rahmouni, Alain; Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Belhadj, Karim; Gaulard, Philippe; Bouanane, Mohamed; Golli, Mondher; Kobeiter, Hicham

2003-12-01

To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

Sediment accretion and organic carbon burial relative to sea-level rise and storm events in two mangrove forests in Everglades National Park

USGS Publications Warehouse

Smoak, Joseph M.; Breithaupt, Joshua L.; Smith, Thomas J.; Sanders, Christian J.

2013-01-01

The goal of this investigation was to examine how sediment accretion and organic carbon (OC) burial rates in mangrove forests respond to climate change. Specifically, will the accretion rates keep pace with sea-level rise, and what is the source and fate of OC in the system? Mass accumulation, accretion and OC burial rates were determined via 210Pb dating (i.e. 100 year time scale) on sediment cores collected from two mangrove forest sites within Everglades National Park, Florida (USA). Enhanced mass accumulation, accretion and OC burial rates were found in an upper layer that corresponded to a well-documented storm surge deposit. Accretion rates were 5.9 and 6.5 mm yr−1 within the storm deposit compared to overall rates of 2.5 and 3.6 mm yr−1. These rates were found to be matching or exceeding average sea-level rise reported for Key West, Florida. Organic carbon burial rates were 260 and 393 g m−2 yr−1 within the storm deposit compared to 151 and 168 g m−2 yr−1 overall burial rates. The overall rates are similar to global estimates for OC burial in marine wetlands. With tropical storms being a frequent occurrence in this region the resulting storm surge deposits are an important mechanism for maintaining both overall accretion and OC burial rates. Enhanced OC burial rates within the storm deposit could be due to an increase in productivity created from higher concentrations of phosphorus within storm-delivered sediments and/or from the deposition of allochthonous OC. Climate change-amplified storms and sea-level rise could damage mangrove forests, exposing previously buried OC to oxidation and contribute to increasing atmospheric CO2 concentrations. However, the processes described here provide a mechanism whereby oxidation of OC would be limited and the overall OC reservoir maintained within the mangrove forest sediments.

Locating the Accretion Footprint on a Herbig Ae Star: MWC 480

NASA Technical Reports Server (NTRS)

Grady, C. A.; Hamaguchi, K.; Schneider, G.; Stecklum, B.; Woodgate, B. E.; McCleary, J. E.; Williger, G. M.; Sitko, M. L.; Menard, F.; Henning, Th.;

Calcium requirements for Asian children and adolescents.

PubMed

Lee, Warren Tak Keung; Jiang, Ji

2008-01-01

Calcium is important for bone health. Over the last 15 years, reference calcium intakes in Western countries have been revised upwards for maximizing bone mass at skeletal maturity and for prevention of osteoporotic fractures. Some of these reference figures have also been adopted for use in Asian countries. However, the scientific data based on for revising reference calcium intakes in the West was largely based on Caucasians. Limited human studies relating to calcium requirements and bone mineralization have been conducted in Asians in Asia. In children and adolescents, a trial has confirmed no effects of calcium supplementation on bone gains in adolescent girls after 7 years. A meta-analysis has also revealed that calcium supplementation has little beneficial effects on bone gain. Given that genetic factors, hormonal status, body size, bone structure, diets, physical activity, vitamin D status and adaptation could modify calcium retention and bone integrity, these factors need to be considered collectively to promote bone health in Asian populations. Furthermore, studies to identify indigenous foods rich in calcium and high in bioavailability are needed to widen sources of dietary calcium. Ethnic differences in calcium retention, hormonal status, bone structure, bone mineral accretion and peak bone mass are evident among Asians, Caucasians and Blacks in USA. Hence, reference calcium intakes for Asians are likely to be unique and different from those of Caucasians. More research has to be conducted in Asian populations in order to develop appropriate reference calcium intakes for the region.

Heat Transfer Measurements on Surfaces with Natural Ice Castings and Modeled Roughness

NASA Technical Reports Server (NTRS)

Breuer, Kenneth S.; Torres, Benjamin E.; Orr, D. J.; Hansman, R. John

1997-01-01

An experimental method is described to measure and compare the convective heat transfer coefficient of natural and simulated ice accretion roughness and to provide a rational means for determining accretion-related enhanced heat transfer coefficients. The natural ice accretion roughness was a sample casting made from accretions at the NASA Lewis Icing Research Tunnel (IRT). One of these castings was modeled using a Spectral Estimation Technique (SET) to produce three roughness elements patterns that simulate the actual accretion. All four samples were tested in a flat-plate boundary layer at angle of attack in a "dry" wind tunnel test. The convective heat transfer coefficient was measured using infrared thermography. It is shown that, dispite some problems in the current data set, the method does show considerable promise in determining roughness-induced heat transfer coefficients, and that, in addition to the roughness height and spacing in the flow direction, the concentration and spacing of elements in the spanwise direction are important parameters.

Two intelligent materials, both of which are self-forming and self-repairing; one also self-senses and recycles

NASA Astrophysics Data System (ADS)

Dry, Carolyn M.

1996-04-01

Two self-forming and repair polymer cementitious composites were developed over a decade apart by the author. Both relied on a nature based paradigm as a model for building, in particular bone formation, repair, and degradation. For the first composite, the proposed material accreted from the ocean, made from a fluids based chemistry, that of seawater. The land based system was not built in-situ but relied on a man made supply of materials which were self-forming, self-repairing and dissolving. But in both cases a fluid based chemistry was necessary for self-building, repair and recycling of a bone-like composite material.

[Sarcoidosis of the skeleton. Review of the literature and case report. (author's transl)].

PubMed

Uehlinger, E; Wurm, K

1976-08-01

The frequency of sarcoidosis in the skeleton varies between 3 and 36%. Skeletal sarcoidosis is rare in early stages (Löfgren-syndrom), relatively frequent in late stages. The initial phase is characterized by the formation of miliary non-caseating epitheloid-cell granulomas in the bone marrow. The invasion of the bone marrow may either be tolerated by the bone tissue or it initiates a perifocal osteosclerosis or a osteolysis. Correspondingly the X-ray of the skeleton shows normal structure or focal osteosclerosis or osteolysis. Therefore in the first case the sarcoidosis cannot be identified by X-ray. Most frequent locations are the phalanges of the fingers and toes, less common the stem skelton (skull, vertebrae, pelvis) and very rare the long tubular bones. In most cases the skeletal sarcoidosis is well tolerated. Report of a case of osteosclerotic sarcoidosis of the pelvis of a 39-years old woman with generalized sarcoidosis which was diagnozed four years earlier. The X-rays of the phalanges were normal. The biopsy of the iliac crest shows miliary sarcoid granuloma of the bone marrow and accretion of lamellar bone on the surface of the bone trabeculi with a distinct mosaic pattern. Treatment with steroids during the following five years was ineffective.

Evidence of Accretion in Saturn's F Ring (Invited)

NASA Astrophysics Data System (ADS)

Agnor, C. B.; Buerle, K.; Murray, C. D.; Evans, M. W.; Cooper, N. J.; Williams, G. W.

2010-12-01

Lying slightly outside the classical Roche radius and being strongly perturbed by the adjacent moons Prometheus and Pandora, Saturn's F ring represents a unique astrophysical laboratory for examining the processes of mass accretion and moonlet formation. Recent images from the Cassini spacecraft reveal optically thick clumps, capable of casting shadows, and associated structures in regions of the F ring following close passage by Prometheus. Here we examine the accretion environment of the F ring and Prometheus' role in moonlet formation and evolution. Using the observed structures adjacent to these clumps and dynamical arguments we estimate the masses of these clumps and find them comparable to that of ~10-20-km contiguous moonlets. Further, we show that Prometheus' perturbations on the F ring create regions of enhanced density and low relative velocity that may accelerate the accretion of clumps and moonlets.

Cytokines and growth factors which regulate bone cell function

NASA Astrophysics Data System (ADS)

Seino, Yoshiki

Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

Stochastic events may lead to accretion in Saturn's rings

NASA Astrophysics Data System (ADS)

Esposito, Larry W.

Stochastic events may lead to accretion in Saturn's rings Larry W. Esposito LASP, University of Colorado UVIS occultations indicate accretion is triggered at the B ring edge, in strong density waves in ring A and in the F ring. Moons may trigger accretion by streamline crowding (Lewis & Stewart); which enhances collisions, leading to accretion; increasing random velocities; leading to more collisions and more accretion. Cassini occultations of these strongly perturbed locations show not only accretion but also disaggregation, with time scales of hours to weeks. The collisions may lead to temporary aggregations via stochastic events: collisions can compress unconsolidated objects, trigger adhesion or bring small pieces into contact with larger or higher-density seeds. Disaggregation then can follow from disruptive collisions or tidal shedding. In the accretion/disruption balance, increased random motions could eventually give the upper hand to disruption. . . just as `irrational exuberance' can lead to financial panic in the economy; or the overpopulation of hares can lead to boom-and-bust in the population of foxes. I present a simple predator-prey model. This system's unstable equilibrium can similarly give rise to episodic cycles in accretion: explaining why the observable ring features that indicate embedded objects have been increasing since the beginning of Cassini's observations of Saturn in 2004. Unlike other interpretations of the peculiar events seen near Saturn Equinox, I emphasize the kinetic description of particle interactions rather than a fluid instability approach; and the dominance of stochastic events involving individual aggregates over free and/or driven modes in a flat disk.

Radiatively-suppressed spherical accretion under relativistic radiative transfer

NASA Astrophysics Data System (ADS)

Fukue, Jun

2018-03-01

We numerically examine radiatively-suppressed relativistic spherical accretion flows on to a central object with mass M under Newtonian gravity and special relativity. We simultaneously solve both the relativistic radiative transfer equation and the relativistic hydrodynamical equations for spherically symmetric flows under the double iteration process in the case of the intermediate optical depth. We find that the accretion flow is suppressed, compared with the freefall case in the nonrelativistic regime. For example, in the case of accretion on to a luminous core with accretion luminosity L*, the freefall velocity v normalized by the speed of light c under the radiative force in the nonrelativistic regime is β (\\hat{r}) = v/c = -√{(1-Γ _*)/(\\hat{r}+1-Γ _*)}, where Γ* (≡ L*/LE, LE being the Eddington luminosity) is the Eddington parameter and \\hat{r} (= r/rS, rS being the Schwarzschild radius) the normalized radius, whereas the infall speed at the central core is ˜0.7β(1), irrespective of the mass-accretion rate. This is due to the relativistic effect; the comoving flux is enhanced by the advective flux. We briefly examine and discuss an isothermal case, where the emission takes place in the entire space.

MINERAL METABOLISM OF FRACTURES OF THE TIBIA IN MAN STUDIED WITH EXTERNAL COUNTING OF Sr$sup 8$$sup 5$

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendberg, B.

1961-01-01

A study was made of 51 adult patients with tibial fractures by external counting with scintillation detectors over the thighs, knees, and tibias during a 14-day period after intravenous injection of 25 to 50 mu c Sr/sup 85/. The pattern of activity curves recorded over the fractured leg compared to those recorded over the control leg varied significantly with the age of the fracture (2 days to 9 yr). Increased uptake of Sr/sup 85/ was observed in all cases. The activity ratio fracture/control tibia obtained 14 days after injection rose during the 1st months after fracture to reach a peakmore » value 6 to 8 months after fracture. The mean 14-day fracture/ control ratios obtained 5 to 10 months after fracture was 15.5 plus or minus 7.2; then it dropped. Even 6 to 9 yr after fracture the counting rate over the fracture was higher than that over the intact tibia. No differences in activity uptake were observed between normally healing fractures and fractures showing delayed or nonunion. Activity curves obtained over the thigh, knee, and tibia of the fractured and intact legs 1 to l4 days after injection of Sr/sup 85/ could be simulated on the basis of a 2-compartment model for the kinetics of Sr in the body. Based on this kinetic analysis the externally recorded Sr/sup 85/ activity values may be interpreted as follows: The activity ratios fractured/intact leg obtained during early intervals after injection are mainly related to differences in the size of the exchangeable mineral spaces under the detector. The 14-day activity ratio of 2 anatomically comparable locations may be used as a relative index of the difference in the accretion rate (rate of irreversible deposition of bone mineral) in these locations, but is somewhat lower than the absolute dfference in the accretion rate. The bone salt laid down in the fracture callus is derived from the body fluids. The accretion rate in the fracture region is increased within a week of the fracture. It rapidly increases during the first months after fracture to reach a peak value at 6 to 8 months after fracture. The accretion rate in the entire fractured leg is increased some months after fracture. The traumatic osteopenia is caused by increased resorption and not by decreased accretion. (H.H.D.)« less

The central spheroids of Milky Way mass-sized galaxies

NASA Astrophysics Data System (ADS)

Tissera, Patricia B.; Machado, Rubens E. G.; Carollo, Daniela; Minniti, Dante; Beers, Timothy C.; Zoccali, Manuela; Meza, Andres

2018-01-01

We study the properties of the central spheroids located within 10 kpc of the centre of mass of Milky Way mass-sized galaxies simulated in a cosmological context. The simulated central regions are dominated by stars older than 10 Gyr, mostly formed in situ, with a contribution of ∼30 per cent from accreted stars. These stars formed in well-defined starbursts, although accreted stars exhibit sharper and earlier ones. The fraction of accreted stars increases with galactocentric distance, so that at a radius of ∼8-10 kpc, a fraction of ∼40 per cent, on average, is detected. Accreted stars are slightly younger, lower metallicity, and more α-enhanced than in situ stars. A significant fraction of old stars in the central regions come from a few (2-3) massive satellites (∼1010 M⊙). The bulge components receive larger contributions of accreted stars formed in dwarfs smaller than ∼109.5 M⊙. The difference between the distributions of ages and metallicities of old stars is thus linked to the accretion histories - those central regions with a larger fraction of accreted stars are those with contributions from more massive satellites. The kinematical properties of in situ and accreted stars are consistent with the latter being supported by their velocity dispersions, while the former exhibit clear signatures of rotational support. Our simulations demonstrate a range of characteristics, with some systems exhibiting a co-existing bar and spheroid in their central regions, resembling in some respect the central region of the Milky Way.

The Association of Fat and Lean Tissue With Whole Body and Spine Bone Mineral Density Is Modified by HIV Status and Sex in Children and Youth.

PubMed

Jacobson, Denise L; Lindsey, Jane C; Coull, Brent A; Mulligan, Kathleen; Bhagwat, Priya; Aldrovandi, Grace M

2018-01-01

HIV-infected (HIV-pos) male children/youth showed lower bone mineral density at sexual maturity than HIV-uninfected (HIV-neg) females. It is not known whether complications of HIV disease, including abnormal body fat distribution, contribute to lower bone accrual in male HIV-pos adolescents. In a cross-sectional study, we evaluated the relationship between body composition (fat and lean mass) and bone mass in HIV-pos and HIV-neg children/youth and determined if it is modified by HIV status and sex. We used generalized estimating equations to simultaneously model the effect of fat/lean mass on multiple bone outcomes, including total body bone mineral density and bone mineral content and spine bone mineral density. We evaluated effect modification by HIV and sex. The analysis cohort consisted of 143 HIV-neg and 236 HIV-pos, of whom 55% were black non-Hispanic and 53% were male. Ages ranged from 7 to < 25 years. Half of the children/youth were at Tanner stage 1 and 20% at Tanner 5. Fat mass was more strongly positively correlated with bone mass in HIV-neg than HIV-pos children/youth and these relationships were more evident for total body bone than spine outcomes. Within HIV strata, fat mass and bone were more correlated in female than male children/youth. The relationship between lean mass and bone varied by sex, but not by HIV status. HIV disease diminishes the positive relationship of greater fat mass on bone mass in children/youth. Disruptions in body fat distribution, which are common in HIV disease, may have an impact on bone accretion during pubertal development.

Numerical Simulations of Wind Accretion in Symbiotic Binaries

NASA Astrophysics Data System (ADS)

de Val-Borro, M.; Karovska, M.; Sasselov, D.

2009-08-01

About half of the binary systems are close enough to each other for mass to be exchanged between them at some point in their evolution, yet the accretion mechanism in wind accreting binaries is not well understood. We study the dynamical effects of gravitational focusing by a binary companion on winds from late-type stars. In particular, we investigate the mass transfer and formation of accretion disks around the secondary in detached systems consisting of an asymptotic giant branch (AGB) mass-losing star and an accreting companion. The presence of mass outflows is studied as a function of mass-loss rate, wind temperature, and binary orbital parameters. A two-dimensional hydrodynamical model is used to study the stability of mass transfer in wind accreting symbiotic binary systems. In our simulations we use an adiabatic equation of state and a modified version of the isothermal approximation, where the temperature depends on the distance from the mass losing star and its companion. The code uses a block-structured adaptive mesh refinement method that allows us to have high resolution at the position of the secondary and resolve the formation of bow shocks and accretion disks. We explore the accretion flow between the components and formation of accretion disks for a range of orbital separations and wind parameters. Our results show the formation of stream flow between the stars and accretion disks of various sizes for certain orbital configurations. For a typical slow and massive wind from an AGB star the flow pattern is similar to a Roche lobe overflow with accretion rates of 10% of the mass loss from the primary. Stable disks with exponentially decreasing density profiles and masses of the order 10-4 solar masses are formed when wind acceleration occurs at several stellar radii. The disks are geometrically thin with eccentric streamlines and close to Keplerian velocity profiles. The formation of tidal streams and accretion disks is found to be weakly dependent on the mass loss from the AGB star. Our simulations of gravitationally focused wind accretion in symbiotic binaries show the formation of stream flows and enhanced accretion rates onto the compact component. We conclude that mass transfer through a focused wind is an important mechanism in wind accreting interacting binaries and can have a significant impact on the evolution of the binary itself and the individual components.

Orbital Light Curves of UU Aquarii in Stunted Outburst

NASA Astrophysics Data System (ADS)

Robertson, J. W.; Honeycutt, R. K.; Henden, A. A.; Campbell, R. T.

2018-02-01

Stunted outbursts are ∼0.ͫ6 eruptions, typically lasting 5–10 days, which are found in some novalike cataclysmic variables, including UU Aqr. The mechanism responsible for stunted outbursts is uncertain but is likely related to an accretion disk instability or to variations in the mass transfer rate. A campaign to monitor the eclipse light curves in UU Aqr has been conducted in order to detect any light curve distortions due to the appearance of a hot spot on the disk at the location of the impact point of the accretion stream. If stunted outbursts are due to a temporary mass transfer enhancement, then predictable deformations of the orbital light curve are expected to occur during such outbursts. This study used 156 eclipses on 135 nights during the years 2000–2012. During this interval, random samples found the system to be in stunted outbursts 4%–5% of the time, yielding ∼7 eclipses obtained during some stage of stunted outburst. About half of the eclipses obtained during stunted outbursts showed clear evidence for hot spot enhancement, providing strong evidence that the stunted outbursts in UU Aqr are associated with mass transfer variations. The other half of the eclipses during stunted outburst showed little or no evidence for hot spot enhancement. Furthermore, there were no systematic changes in the hot spot signature as stunted outbursts progressed. Therefore, we have tentatively attributed the changes in hot spot visibility during stunted outburst to random blobby accretion, which likely further modulates the strength of the accretion stream on orbital timescales.

X-Ray Enhancement and Long-term Evolution of Swift J1822.3-1606

NASA Astrophysics Data System (ADS)

Benli, Onur; Çalışkan, Ş.; Ertan, Ü.; Alpar, M. A.; Trümper, J. E.; Kylafis, N. D.

2013-12-01

We investigate the X-ray enhancement and the long-term evolution of the recently discovered second "low-B magnetar" Swift J1822.3-1606 in the frame of the fallback disk model. During a soft gamma burst episode, the inner disk matter is pushed back to larger radii, forming a density gradient at the inner disk. Subsequent relaxation of the inner disk could account for the observed X-ray enhancement light curve of Swift J1822.3-1606. We obtain model fits to the X-ray data with basic disk parameters similar to those employed to explain the X-ray outburst light curves of other anomalous X-ray pulsars and soft gamma repeaters. The long period (8.4 s) of the neutron star can be reached by the effect of the disk torques in the long-term accretion phase ((1-3) × 105 yr). The currently ongoing X-ray enhancement could be due to a transient accretion epoch, or the source could still be in the accretion phase in quiescence. Considering these different possibilities, we determine the model curves that could represent the long-term rotational and the X-ray luminosity evolution of Swift J1822.3-1606, which constrain the strength of the magnetic dipole field to the range of (1-2) × 1012 G on the surface of the neutron star.

Torque Enhancement, Spin Equilibrium, and Jet Power from Disk-Induced Opening of Pulsar Magnetic Fields

NASA Astrophysics Data System (ADS)

Parfrey, Kyle; Spitkovsky, Anatoly; Beloborodov, Andrei M.

2016-05-01

The interaction of a rotating star’s magnetic field with a surrounding plasma disk lies at the heart of many questions posed by neutron stars in X-ray binaries. We consider the opening of stellar magnetic flux due to differential rotation along field lines coupling the star and disk, using a simple model for the disk-opened flux, the torques exerted on the star by the magnetosphere, and the power extracted by the electromagnetic wind. We examine the conditions under which the system enters an equilibrium spin state, in which the accretion torque is instantaneously balanced by the pulsar wind torque alone. For magnetic moments, spin frequencies, and accretion rates relevant to accreting millisecond pulsars, the spin-down torque from this enhanced pulsar wind can be substantially larger than that predicted by existing models of the disk-magnetosphere interaction, and is in principle capable of maintaining spin equilibrium at frequencies less than 1 kHz. We speculate that this mechanism may account for the non-detection of frequency increases during outbursts of SAX J1808.4-3658 and XTE J1814-338, and may be generally responsible for preventing spin-up to sub-millisecond periods. If the pulsar wind is collimated by the surrounding environment, the resulting jet can satisfy the power requirements of the highly relativistic outflows from Cir X-1 and Sco X-1. In this framework, the jet power scales relatively weakly with accretion rate, {L}{{j}}\\propto {\\dot{M}}4/7, and would be suppressed at high accretion rates only if the stellar magnetic moment is sufficiently low.

Ice Accretion Roughness Measurements and Modeling

NASA Technical Reports Server (NTRS)

McClain, Stephen T.; Vargas, Mario; Tsao, Jen-Ching; Broeren, Andy P.; Lee, Sam

2017-01-01

Roughness on aircraft ice accretions is very important to the overall ice accretion process and to the resulting degradation in aircraft aerodynamic performance. Roughness enhances the local convection leading to more rapid ice accumulation rates, and roughness generates local flow perturbations that lead to higher skin friction. This paper presents 1) a review of the developments in ice shape three-dimensional laser scanning developed at NASA Glenn, 2) a review of the approach of McClain and Kreeger employed to characterize ice roughness evolution on an airfoil surface, and 3) a review of the experimental efforts that have been performed over the last five years to characterize, scale, and model ice roughness evolution physics.

The profiles of Fe K α line from the inhomogeneous accretion flow

NASA Astrophysics Data System (ADS)

Yu, Xiao-Di; Ma, Ren-Yi; Li, Ya-Ping; Zhang, Hui; Fang, Tao-Tao

2018-05-01

The clumpy disc, or inhomogeneous accretion flow, has been proposed to explain the properties of accreting black hole systems. However, the observational evidence remains to be explored. In this work, we calculate the profiles of Fe K α lines emitted from the inhomogeneous accretion flow through the ray-tracing technique, in order to find possible observable signals of the clumps. Compared with the skewed double-peaked profile of the continuous standard accretion disc, the lines show a multipeak structure when the emissivity index is not very steep. The peaks and wings are affected by the position and size of the cold clumps. When the clump is small and is located in the innermost region, due to the significant gravitational redshift, the blue wing can overlap with the red wing of the outer cold disc/clump, forming a fake peak or greatly enhancing the red peak. Given high enough resolution, it is easier to constrain the clumps around the supermassive black holes than the clumps in stellar mass black holes due to the thermal Doppler effect.

Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

PubMed

Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

2016-08-01

This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.

Time-series Photometry of the Pre-Main Sequence Binary V4046 Sgr: Testing the Accretion Stream Theory

NASA Astrophysics Data System (ADS)

Tofflemire, Benjamin M.; Mathieu, Robert D.; Ardila, David R.; Ciardi, David R.

2015-01-01

Most stars are born in binaries, and the evolution of protostellar disks in pre-main sequence (PMS) binary stars is a current frontier of star formation research. PMS binary stars can have up to three accretion disks: two circumstellar disks and a circumbinary disk separated by a dynamically cleared gap. Theory suggests that mass may periodically flow in an accretion stream from a circumbinary disk across the gap onto circumstellar disks or stellar surfaces. Thus, accretion in PMS binaries is controlled by not only radiation, disk viscosity, and magnetic fields, but also by orbital dynamics.As part of a larger, ongoing effort to characterize mass accretion in young binary systems, we test the predictions of the binary accretion stream theory through continuous, multi-orbit, multi-color optical and near-infrared (NIR) time-series photometry. Observations such as these are capable of detecting and characterizing these modulated accretion streams, if they are generally present. Broad-band blue and ultraviolet photometry trace the accretion luminosity and photospheric temperature while NIR photometry provide a measurement of warm circumstellar material, all as a function of orbital phase. The predicted phase and magnitude of enhanced accretion are highly dependent on the binary orbital parameters and as such, our campaign focuses on 10 PMS binaries of varying periods and eccentricities. Here we present multi-color optical (U, B,V, R), narrowband (Hα), and multi-color NIR (J, H) lightcurves of the PMS binary V4046 Sgr (P=2.42 days) obtained with the SMARTS 1.3m telescope and LCOGT 1m telescope network. These results act to showcase the quality and breadth of data we have, or are currently obtaining, for each of the PMS binaries in our sample. With the full characterization of our sample, these observations will guide an extension of the accretion paradigm from single young stars to multiple systems.

Modulated mass-transfer model for superhumps in SU Ursae Majoris stars

NASA Technical Reports Server (NTRS)

Mineshige, Shin

1988-01-01

The response of a circular accretion disk to rapid modulation of the mass-transfer rate into the disk is explored in order to model superhumps in SU UMa stars. It is proposed that periodically enhanced flow may disrupt or heat up the outer disk and produce the dips noted just before the superhump peaks. The elliptical accretion-disk model with extended vertical disk structure can account for the observed characteristics of superhumps in these stars.

Formation of massive seed black holes via collisions and accretion

NASA Astrophysics Data System (ADS)

Boekholt, T. C. N.; Schleicher, D. R. G.; Fellhauer, M.; Klessen, R. S.; Reinoso, B.; Stutz, A. M.; Haemmerlé, L.

2018-05-01

Models aiming to explain the formation of massive black hole seeds, and in particular the direct collapse scenario, face substantial difficulties. These are rooted in rather ad hoc and fine-tuned initial conditions, such as the simultaneous requirements of extremely low metallicities and strong radiation backgrounds. Here, we explore a modification of such scenarios where a massive primordial star cluster is initially produced. Subsequent stellar collisions give rise to the formation of massive (104-105 M⊙) objects. Our calculations demonstrate that the interplay among stellar dynamics, gas accretion, and protostellar evolution is particularly relevant. Gas accretion on to the protostars enhances their radii, resulting in an enhanced collisional cross-section. We show that the fraction of collisions can increase from 0.1 to 1 per cent of the initial population to about 10 per cent when compared to gas-free models or models of protostellar clusters in the local Universe. We conclude that very massive objects can form in spite of initial fragmentation, making the first massive protostellar clusters viable candidate birth places for observed supermassive black holes.

General Relativistic Radiative Transfer and General Relativistic MHD Simulations of Accretion and Outflows of Black Holes

NASA Technical Reports Server (NTRS)

Fuerst, Steven V.; Mizuno, Yosuke; Nishikawa, Ken-Ichi; Wu, Kinwah

2007-01-01

We have calculated the emission from relativistic flows in black hole systems using a fully general relativistic radiative transfer, with flow structures obtained by general relativistic magnetohydrodynamic simulations. We consider thermal free-free emission and thermal synchrotron emission. Bright filament-like features are found protruding (visually) from the accretion disk surface, which are enhancements of synchrotron emission when the magnetic field is roughly aligned with the line-of-sight in the co-moving frame. The features move back and forth as the accretion flow evolves, but their visibility and morphology are robust. We propose that variations and location drifts of the features are responsible for certain X-ray quasi-periodic oscillations (QPOs) observed in black-hole X-ray binaries.

General Relativistic Radiative Transfer and GeneralRelativistic MHD Simulations of Accretion and Outflows of Black Holes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fuerst, Steven V.; /KIPAC, Menlo Park; Mizuno, Yosuke

2007-01-05

We calculate the emission from relativistic flows in black hole systems using a fully general relativistic radiative transfer formulation, with flow structures obtained by general relativistic magneto-hydrodynamic simulations. We consider thermal free-free emission and thermal synchrotron emission. Bright filament-like features protrude (visually) from the accretion disk surface, which are enhancements of synchrotron emission where the magnetic field roughly aligns with the line-of-sight in the co-moving frame. The features move back and forth as the accretion flow evolves, but their visibility and morphology are robust. We propose that variations and drifts of the features produce certain X-ray quasi-periodic oscillations (QPOs) observedmore » in black-hole X-ray binaries.« less

Relation of adrenal-derived steroids with bone maturation, mineral density and geometry in healthy prepubertal and early pubertal boys.

PubMed

Vandewalle, S; Taes, Y; Fiers, T; Toye, K; Van Caenegem, E; Kaufman, J-M; De Schepper, J

2014-12-01

Little is known about the effects of adrenal steroids on skeletal maturation and bone mass acquisition in healthy prepubertal boys. To study whether adrenal-derived steroids within the physiological range are associated with skeletal maturation, areal and volumetric bone mineral density (aBMD and vBMD) and bone geometry in healthy prepubertal and early pubertal boys. 98 healthy prepubertal and early pubertal boys (aged 6-14 y) were studied cross-sectionally. Androstenedione (A) and estrone (E1) were determined by liquid chromatography tandem mass spectrometry and DHEAS was determined by immunoassay. Whole body and lumbar spine aBMD and bone area were determined by dual-energy X-ray absorptiometry. Trabecular (distal site) and cortical (proximal site) vBMD and bone geometry were assessed at the non-dominant forearm and leg using peripheral QCT. Skeletal age was determined by X-ray of the left hand. Adrenal-derived steroids (DHEAS, A and E1) are positively associated with bone age in prepubertal and early pubertal children, independently of age. There are no associations between the adrenal-derived steroids and the studied parameters of bone size (lumbar spine and whole body bone area, trabecular or cortical area at the radius or tibia, periosteal circumference and cortical thickness at the radius or tibia) or BMD (aBMD or vBMD). In healthy prepubertal and early pubertal boys, serum adrenal-derived steroid levels, are associated with skeletal maturation, independently of age, but not with bone size or (v)BMD. Our data suggest that adrenal derived steroids are not implicated in the accretion of bone mass before puberty in boys. Copyright © 2014 Elsevier Inc. All rights reserved.

A search for passive protoplanetary discs in the Taurus-Auriga star-forming region

NASA Astrophysics Data System (ADS)

Duchêne, Gaspard; Becker, Adam; Yang, Yizhe; Bouy, Hervé; De Rosa, Robert J.; Patience, Jennifer; Girard, Julien H.

2017-08-01

We conducted a 12-month monitoring campaign of 33 T Tauri stars (TTS) in Taurus. Our goal was to monitor objects that possess a disc but have a weak H α line, a common accretion tracer for young stars, in order to determine whether they host a passive circumstellar disc. We used medium-resolution optical spectroscopy to assess the accretion status of the objects and to measure the H α line. We found no convincing examples of passive discs: only transition disc and debris disc systems in our sample are non-accreting. Among accretors, we found no example of flickering accretion, leading to an upper limit of 2.2 per cent on the duty cycle of accretion gaps, assuming that all accreting TTS experience such events. When combining literature results with our observations, we found that the reliability of traditional H α-based criteria to test for accretion is high but imperfect, particularly for low-mass TTS. We found a significant correlation between stellar mass and the full width at 10 per cent of the peak (W10) of the H α line that does not seem to be related to variations in free-fall velocity. Finally, our data revealed a positive correlation between the H α equivalent width and its W10, indicative of a systematic modulation in the line profile whereby the high-velocity wings of the line are proportionally more enhanced than its core when the line luminosity increases. We argue that this supports the hypothesis that the mass accretion rate on the central star is correlated with the H α W10 through a common physical mechanism.

The influence of microlensing on spectral line shapes generated by a relativistic accretion disc

NASA Astrophysics Data System (ADS)

Popović, L. Č; Mediavilla, E. G.; Muñoz, J. A.

2001-10-01

We study the influence of gravitational microlensing on the spectral line profiles originating from a relativistic accretion disc. Using the Chen & Halpern model for the disc, we show the noticeable changes that microlensing can induce in the line shape when the Einstein radius associated with the microlens is of a size comparable to that of the accretion disc. Of special interest is the relative enhancement between the blue and red peaks of the line when an off-center microlens affects the approaching and receding parts of the accretion disc asymmetrically. In an AGN formed by a super-massive binary in which the accretion disc is located around one of the super-massive companions (the primary), we discuss the possibility of microlensing by the secondary. In this case the ratio between the blue and red peaks of the line profile would depend on the orbital phase. We have also considered the more standard configuration of microlensing by a star-sized object in an intervening galaxy and find that microlensing may also be detected in the broad emission lines of multiply imaged QSOs. The changes observed in the line profile of Arp 102 B are taken as a reference for exploring both scenarios.

How Turbulence Can Set the Radial Distribution of Gas Giants Formed by Pebble Accretion

NASA Astrophysics Data System (ADS)

Morley Rosenthal, Mickey; Murray-Clay, Ruth

2018-04-01

I discuss how turbulence impacts the orbital separation at which the cores of gas giants can form via pebble accretion. While pebble accretion is extremely rapid for massive planets, I demonstrate that pebble accretion is inhibited at protoplanet masses, an effect which is strongly enhanced in a turbulent disk. Using these considerations I derive a “minimum” mass, past which pebble accretion proceeds on timescales less than the disk lifetime. By considering core formation where early growth to this minimum mass proceeds by gravitational focusing of planetesimals, I demonstrate that the the semi-major axes where gas giants can form are more restricted as the strength of the nebular turbulence increases — e.g. formation can only occur at distances < 30 AU for α > 10^-2. I also examine the implications of turbulence on the mass gas giants can reach before opening a substantial gap and halting growth. I find that while weak turbulence allows gas giants to form far out in the disk, the masses of these planets are substantially lower (< 1 Jupiter mass), which would preclude them from having been detected by the current generation of direct imaging surveys.

The Influence of Stellar Spin on Ignition of Thermonuclear Runaways

NASA Astrophysics Data System (ADS)

Galloway, Duncan K.; in ’t Zand, Jean J. M.; Chenevez, Jérôme; Keek, Laurens; Sanchez-Fernandez, Celia; Worpel, Hauke; Lampe, Nathanael; Kuulkers, Erik; Watts, Anna; Ootes, Laura; The MINBAR collaboration

2018-04-01

Runaway thermonuclear burning of a layer of accumulated fuel on the surface of a compact star provides a brief but intense display of stellar nuclear processes. For neutron stars accreting from a binary companion, these events manifest as thermonuclear (type-I) X-ray bursts, and recur on typical timescales of hours to days. We measured the burst rate as a function of accretion rate, from seven neutron stars with known spin rates, using a burst sample accumulated over several decades. At the highest accretion rates, the burst rate is lower for faster spinning stars. The observations imply that fast (>400 Hz) rotation encourages stabilization of nuclear burning, suggesting a dynamical dependence of nuclear ignition on the spin rate. This dependence is unexpected, because faster rotation entails less shear between the surrounding accretion disk and the star. Large-scale circulation in the fuel layer, leading to enhanced mixing of the burst ashes into the fuel layer, may explain this behavior; further numerical simulations are required to confirm this.

Elemental compositions of two extrasolar rocky planetesimals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, S.; Jura, M.; Klein, B.

2014-03-10

We report Keck/HIRES and Hubble Space Telescope/COS spectroscopic studies of extrasolar rocky planetesimals accreted onto two hydrogen atmosphere white dwarfs, G29-38 and GD 133. In G29-38, eight elements are detected, including C, O, Mg, Si, Ca, Ti, Cr, and Fe while in GD 133, O, Si, Ca, and marginally Mg are seen. These two extrasolar planetesimals show a pattern of refractory enhancement and volatile depletion. For G29-38, the observed composition can be best interpreted as a blend of a chondritic object with some refractory-rich material, a result from post-nebular processing. Water is very depleted in the parent body accreted ontomore » G29-38, based on the derived oxygen abundance. The inferred total mass accretion rate in GD 133 is the lowest of all known dusty white dwarfs, possibly due to non-steady state accretion. We continue to find that a variety of extrasolar planetesimals all resemble to zeroth order the elemental composition of bulk Earth.« less

Gas Accretion and Star Formation Rates

NASA Astrophysics Data System (ADS)

Sánchez Almeida, Jorge

Cosmological numerical simulations of galaxy evolution show that accretion of metal-poor gas from the cosmic web drives the star formation in galaxy disks. Unfortunately, the observational support for this theoretical prediction is still indirect, and modeling and analysis are required to identify hints as actual signs of star formation feeding from metal-poor gas accretion. Thus, a meticulous interpretation of the observations is crucial, and this observational review begins with a simple theoretical description of the physical process and the key ingredients it involves, including the properties of the accreted gas and of the star formation that it induces. A number of observations pointing out the connection between metal-poor gas accretion and star formation are analyzed, specifically, the short gas-consumption time-scale compared to the age of the stellar populations, the fundamental metallicity relationship, the relationship between disk morphology and gas metallicity, the existence of metallicity drops in starbursts of star-forming galaxies, the so-called G dwarf problem, the existence of a minimum metallicity for the star-forming gas in the local universe, the origin of the α-enhanced gas forming stars in the local universe, the metallicity of the quiescent BCDs, and the direct measurements of gas accretion onto galaxies. A final section discusses intrinsic difficulties to obtain direct observational evidence, and points out alternative observational pathways to further consolidate the current ideas.

Enhancer of Zeste Homolog 2 Inhibition Stimulates Bone Formation and Mitigates Bone Loss Caused by Ovariectomy in Skeletally Mature Mice*

PubMed Central

Dudakovic, Amel; Camilleri, Emily T.; Riester, Scott M.; Paradise, Christopher R.; Gluscevic, Martina; O'Toole, Thomas M.; Thaler, Roman; Evans, Jared M.; Yan, Huihuang; Subramaniam, Malayannan; Hawse, John R.; Stein, Gary S.; Montecino, Martin A.; McGee-Lawrence, Meghan E.; Westendorf, Jennifer J.; van Wijnen, Andre J.

2016-01-01

Perturbations in skeletal development and bone degeneration may result in reduced bone mass and quality, leading to greater fracture risk. Bone loss is mitigated by bone protective therapies, but there is a clinical need for new bone-anabolic agents. Previous work has demonstrated that Ezh2 (enhancer of zeste homolog 2), a histone 3 lysine 27 (H3K27) methyltransferase, suppressed differentiation of osteogenic progenitors. Here, we investigated whether inhibition of Ezh2 can be leveraged for bone stimulatory applications. Pharmacologic inhibition and siRNA knockdown of Ezh2 enhanced osteogenic commitment of MC3T3 preosteoblasts. Next generation RNA sequencing of mRNAs and real time quantitative PCR profiling established that Ezh2 inactivation promotes expression of bone-related gene regulators and extracellular matrix proteins. Mechanistically, enhanced gene expression was linked to decreased H3K27 trimethylation (H3K27me3) near transcriptional start sites in genome-wide sequencing of chromatin immunoprecipitations assays. Administration of an Ezh2 inhibitor modestly increases bone density parameters of adult mice. Furthermore, Ezh2 inhibition also alleviated bone loss in an estrogen-deficient mammalian model for osteoporosis. Ezh2 inhibition enhanced expression of Wnt10b and Pth1r and increased the BMP-dependent phosphorylation of Smad1/5. Thus, these data suggest that inhibition of Ezh2 promotes paracrine signaling in osteoblasts and has bone-anabolic and osteoprotective potential in adults. PMID:27758858

Segmentation of knee MRI using structure enhanced local phase filtering

NASA Astrophysics Data System (ADS)

Lim, Mikhiel; Hacihaliloglu, Ilker

2016-03-01

The segmentation of bone surfaces from magnetic resonance imaging (MRI) data has applications in the quanti- tative measurement of knee osteoarthritis, surgery planning for patient specific total knee arthroplasty and its subsequent fabrication of artificial implants. However, due to the problems associated with MRI imaging such as low contrast between bone and surrounding tissues, noise, bias fields, and the partial volume effect, segmentation of bone surfaces continues to be a challenging operation. In this paper, a new framework is presented for the enhancement of knee MRI scans prior to segmentation in order to obtain high contrast bone images. During the first stage, a new contrast enhanced relative total variation (RTV) regularization method is used in order to remove textural noise from the bone structures and surrounding soft tissue interface. This salient bone edge information is further enhanced using a sparse gradient counting method based on L0 gradient minimization, which globally controls how many non-zero gradients are resulted in order to approximate prominent bone structures in a structure-sparsity-management manner. The last stage of the framework involves incorporation of local phase bone boundary information in order to provide an intensity invariant enhancement of contrast between the bone and surrounding soft tissue. The enhanced images are segmented using a fast random walker algorithm. Validation against expert segmentation was performed on 10 clinical knee MRI images, and achieved a mean dice similarity coefficient (DSC) of 0.975.

Pattern of uptake of americium-241 by the rat skeleton and its subsequent redistribution and retention: implications for human dosimetry and toxicology.

PubMed

Priest, N D; Howells, G; Green, D; Haines, J W

1983-01-01

The distribution and retention of intravenously injected 241Am in the skeleton of the female rat has been investigated using autoradiographic and radiochemical techniques. The studies were designed to assess the dosimetric and toxicologic implications of an 241Am intake by man. They showed that in the rat approximately one third of the intravenously injected 241Am was deposited in the skeleton where it appeared to be retained with a long biological half-time. The studies also showed: 1 241Am is initially deposited onto all types of bone surface including endosteal surfaces, periosteal surfaces and those of the vascular canals within cortical bone, but seems to be preferentially deposited onto those that are resorbing, 2 Bone accretion results in the burial of surface deposits of 241Am, 3 Bone resorption causes the removal of 241Am from surfaces, 4 Resorbed 241Am is retained by phagocytic cells (probably macrophages) in the bone marrow, 5 The transfer of 241Am from the phagocytic cells in the marrow to adjacent bone surfaces seems to occur, (local recycling). 6 The possibility that some of the 241Am removed from the bone surfaces enters the blood and is redeposited in bone, (systemic recycling) cannot be dismissed. These results show that 241Am deposition and redistribution in bone shares many characteristics with other 'bone surface-seeking radionuclides' typified by 239Pu. Consequently, it is suggested that a similar model to that used to calculate annual limits of intake for 239Pu in man would be suitable for the calculation of corresponding values for the 241Am isotopes.

Specific Biomimetic Hydroxyapatite Nanotopographies Enhance Osteoblastic Differentiation and Bone Graft Osteointegration

PubMed Central

Loiselle, Alayna E.; Wei, Lai; Faryad, Muhammad; Paul, Emmanuel M.; Lewis, Gregory S.; Gao, Jun; Lakhtakia, Akhlesh

2013-01-01

Impaired healing of cortical bone grafts represents a significant clinical problem. Cadaveric bone grafts undergo extensive chemical processing to decrease the risk of disease transmission; however, these processing techniques alter the bone surface and decrease the osteogenic potential of cells at the healing site. Extensive work has been done to optimize the surface of bone grafts, and hydroxyapatite (HAP) and nanotopography both increase osteoblastic differentiation. HAP is the main mineral component of bone and can enhance osteoblastic differentiation and bone implant healing in vivo, while nanotopography can enhance osteoblastic differentiation, adhesion, and proliferation. This is the first study to test the combined effects of HAP and nanotopographies on bone graft healing. With the goal of identifying the optimized surface features to improve bone graft healing, we tested the hypothesis that HAP-based nanotopographic resurfacing of bone grafts improves integration of cortical bone grafts by enhancing osteoblastic differentiation. Here we show that osteoblastic cells cultured on processed bones coated with specific-scale (50–60 nm) HAP nanotopographies display increased osteoblastic differentiation compared to cells on uncoated bone, bones coated with poly-l-lactic acid nanotopographies, or other HAP nanotopographies. Further, bone grafts coated with 50–60-nm HAP exhibited increased formation of new bone and improved healing, with mechanical properties equivalent to live autografts. These data indicate the potential for specific HAP nanotopographies to not only increase osteoblastic differentiation but also improve bone graft incorporation, which could significantly increase patient quality of life after traumatic bone injuries or resection of an osteosarcoma. PMID:23510012

Rotational mixing in carbon-enhanced metal-poor stars with s-process enrichment

NASA Astrophysics Data System (ADS)

Matrozis, E.; Stancliffe, R. J.

2017-10-01

Carbon-enhanced metal-poor (CEMP) stars with s-process enrichment (CEMP-s) are believed to be the products of mass transfer from an asymptotic giant branch (AGB) companion, which has long since become a white dwarf. The surface abundances of CEMP-s stars are thus commonly assumed to reflect the nucleosynthesis output of the first AGB stars. We have previously shown that, for this to be the case, some physical mechanism must counter atomic diffusion (gravitational settling and radiative levitation) in these nearly fully radiative stars, which otherwise leads to surface abundance anomalies clearly inconsistent with observations. Here we take into account angular momentum accretion by these stars. We compute in detail the evolution of typical CEMP-s stars from the zero-age main sequence, through the mass accretion, and up the red giant branch for a wide range of specific angular momentum ja of the accreted material, corresponding to surface rotation velocities, vrot, between about 0.3 and 300 kms-1. We find that only for ja ≳ 1017 cm2s-1 (vrot > 20 kms-1, depending on mass accreted) angular momentum accretion directly causes chemical dilution of the accreted material. This could nevertheless be relevant to CEMP-s stars, which are observed to rotate more slowly, if they undergo continuous angular momentum loss akin to solar-like stars. In models with rotation velocities characteristic of CEMP-s stars, rotational mixing primarily serves to inhibit atomic diffusion, such that the maximal surface abundance variations (with respect to the composition of the accreted material) prior to first dredge-up remain within about 0.4 dex without thermohaline mixing or about 0.5-1.5 dex with thermohaline mixing. Even in models with the lowest rotation velocities (vrot ≲ 1 kms-1), rotational mixing is able to severely inhibit atomic diffusion, compared to non-rotating models. We thus conclude that it offers a natural solution to the problem posed by atomic diffusion and cannot be neglected in models of CEMP-s stars. A quantitative summary of the models presented in this paper (mainly the stellar properties and surface abundances at key points of the evolution) is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/606/A55

Bone Mineral Density of Indian Children and Adolescents with Cystic Fibrosis.

PubMed

Gupta, Sumita; Mukherjee, Aparna; Khadgawat, Rajesh; Kabra, Madhulika; Lodha, Rakesh; Kabra, Sushil K

2017-07-15

To document bone mineral density of children and adolescents with cystic fibrosis. Cross-sectional study. Tertiary-care center of Northern India, July 2012 to August 2015. 52 children aged 6-18 years with cystic fibrosis and 62 healthy controls of similar age and sex. Both patients and controls were stratified into two groups, as pre-pubertal and peri-/post-pubertal, and compared for whole body bone mineral density, measured using dual energy X-ray absorptiometry. Serum levels of calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D and parathyroid hormone were measured in children with cystic fibrosis. Compared with controls, the mean (SD) bone mineral density of children with cystic fibrosis was significantly lower in both the pre-pubertal (0.7 (0.1) g/cm2 vs 0.9 (0.1) g/cm2; P<0.001)) and peri-/post-pubertal groups (0.9 (0.1) g/cm2 vs 1.1 (0.1) g/cm2; P<0.001). Also, the mean (SD) bone mineral apparent density of pre-pubertal and peri-/post-pubertal cystic fibrosis patients was lower than the controls (P <0.001 and P= 0.01, respectively). Thirty-seven (71.2%) cystic fibrosis patients had serum 25-hydroxyvitamin D level below 15 ng/mL. Bone mineral density of children with cystic fibrosis was significantly lower than controls; majority of them were vitamin-D deficient. Intervening at an early stage of the disease and providing optimal therapy involving simultaneous management of the several factors affecting bone mineral accretion may be beneficial in improving bone health of these patients.

Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

PubMed

Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

2016-09-01

Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

Infrared observations of white dwarfs and the implications for the accretion of dusty planetary material

NASA Astrophysics Data System (ADS)

Bonsor, Amy; Farihi, Jay; Wyatt, Mark C.; van Lieshout, Rik

2017-06-01

Infrared excesses around metal-polluted white dwarfs have been associated with the accretion of dusty planetary material. This work analyses the available infrared data for an unbiased sample of white dwarfs and demonstrates that no more than 3.3 per cent can have a wide, flat, opaque dust disc, extending to the Roche radius, with a temperature at the disc inner edge of Tin = 1400 K, the standard model for the observed excesses. This is in stark contrast to the incidence of pollution of about 30 per cent. We present four potential reasons for the absence of an infrared excess in polluted white dwarfs, depending on their stellar properties and inferred accretion rates: (I) their dust discs are opaque, but narrow, thus evading detection if more than 85 per cent of polluted white dwarfs have dust discs narrower than δr < 0.04r, (II) their dust discs have been fully consumed, which only works for the oldest white dwarfs with sinking time-scales longer than hundreds of years, (III) their dust is optically thin, which can supply low accretion rates of <107 gs-1 if dominated by (Poynting-Robertson) PR-drag, and higher accretion rates, if inwards transport of material is enhanced, e.g. due to the presence of gas, (IV) their accretion is supplied by a pure gas disc, which could result from the sublimation of optically thin dust for T* > 20 000 K. Future observations sensitive to faint infrared excesses or the presence of gas can test the scenarios presented here, thereby better constraining the nature of the material fuelling accretion in polluted white dwarfs.

Neutron and antineutron production in accretion onto compact objects

NASA Technical Reports Server (NTRS)

Dermer, C. D.; Ramaty, R.

1986-01-01

Nuclear reactions in the hot accretion plasma surrounding a collapsed star are a source of neutrons, primarily through spallation and pion-producing reactions, and antineutrons, principally through the reaction p+p yields p+p+n+anti-n. We calculate spectra of neutrons and antineutrons produced by a variety of nonthermal energetic particle distributions in which the target particles are either at rest or in motion. If only neutral particles are free to escape the interaction site, a component of the proton and antiproton fluxes in the cosmic radiation results from the neutrons and antineutrons which leave the accretion plasma and subsequently decay in the interstellar medium. This additional antiproton component could account for the enhanced flux of antiprotons in the cosmic radiation, compared to values expected from the standard leaky-box model of cosmic-ray propagation and confinement. Moreover, the low-energy antiproton flux measured by Buffington et al. (1981) could result from target-particle motion in the accretion plasma. This model for the origin of antiprotons predicts a narrow 2.223 MeV line which could be observable.

Towards optical brain imaging: getting light through a bone

NASA Astrophysics Data System (ADS)

Thompson, J. V.; Hokr, B. H.; Nodurft, D. T.; Yakovlev, V. V.

2018-06-01

Optical imaging and detection in biological samples is severely limited by scattering effects. In particular, optical techniques for measuring conditions beneath the skull and within the bone marrow hold significant promise when it comes to speed, sensitivity and specificity. However, the strong optical scattering due to bone hinders the realization of these methods. In this article, we propose a technique to enhance the transmittance of light through bone. This is achieved by injecting light below the top surface of the bone and utilizing multiple scattering to increase transmittance. This technique suggests that enhancements of 2-6 times may be realized by injection of light 1 mm below the surface of the bone. By enhancing the transmittance of light through bone, we will greatly improve our ability to utilize optical methods to better understand and diagnose conditions within biological media.

Continued Investigations of the Accretion History of Extraterrestrial Matter over Geologic Time

NASA Technical Reports Server (NTRS)

Farley, Kenneth

2001-01-01

This grant supported our ongoing project to characterize the accretion rate of interplanetary dust particles (IDPs) to Earth over geologic time using He-3 as a tracer. IDPs are derived from collisions in the asteroid belt and from disaggregation of active comets. Owing to their small size (few to few hundred micrometers diameter) these particles spiral into the sun under Poynting-Robertson drag typically in less than a few tens of kyrs. Thus IDPs must be continually resupplied to the zodiacal cloud, and because the processes of IDP production are likely to be sporadic, time variation in the IDP accretion rate to Earth is likely to be time-varying. For example, major asteroidal collisions and comet showers should greatly enhance the IDP accretion rate. Our ultimate objective (still ongoing) is to document this time variance so as to better understand the history of the solar system, the source of IDPs accreting to Earth, and the details of the mechanism by which particles are captured by Earth. To document variations in IDP accretion rate through time we use He-3 as a tracer. This isotope is in extremely low abundance in terrestrial matter, but IDPs have very high concentrations of He-3 from implantation of solar wind ions. By measuring He-3 in seafloor sediments, we can estimate the IDP accretion rate for at least the last few hundred Myrs. Under an earlier NASA grant we identified the existence of a large increase in He-3 flux in the Late Eocene (35 Myr ago), coincident with the two largest impact craters of the Cenozoic Era. The simplest interpretation of this observation is the occurrence of a shower of long period comets at that time, simultaneously increasing the impact cratering probability and accretion rate of IDPs to Earth (Farley et al., 1998). Comet showers produced by stellar perturbation of the Oort cloud should be fairly common in the geologic record, so this is not an unreasonable interpretation of our observations.

Bone morphogenetic protein (BMP)1-3 enhances bone repair.

PubMed

Grgurevic, Lovorka; Macek, Boris; Mercep, Mladen; Jelic, Mislav; Smoljanovic, Tomislav; Erjavec, Igor; Dumic-Cule, Ivo; Prgomet, Stefan; Durdevic, Dragan; Vnuk, Drazen; Lipar, Marija; Stejskal, Marko; Kufner, Vera; Brkljacic, Jelena; Maticic, Drazen; Vukicevic, Slobodan

2011-04-29

Members of the astacin family of metalloproteinases such as human bone morphogenetic protein 1 (BMP-1) regulate morphogenesis by processing precursors to mature functional extracellular matrix (ECM) proteins and several growth factors including TGFβ, BMP2, BMP4 and GFD8. We have recently discovered that BMP1-3 isoform of the Bmp-1 gene circulates in the human plasma and is significantly increased in patients with acute bone fracture. We hypothesized that circulating BMP1-3 might have an important role in bone repair and serve as a novel bone biomarker. When administered systemically to rats with a long bone fracture and locally to rabbits with a critical size defect of the ulna, recombinant human BMP1-3 enhanced bone healing. In contrast, neutralization of the endogenous BMP1-3 by a specific polyclonal antibody delayed the bone union. Invitro BMP1-3 increased the expression of collagen type I and osteocalcin in MC3T3-E(1) osteoblast like cells, and enhanced the formation of mineralized bone nodules from bone marrow mesenchymal stem cells. We suggest that BMP1-3 is a novel systemic regulator of bone repair. Copyright © 2011 Elsevier Inc. All rights reserved.

Microcracks induce osteoblast alignment and maturation on hydroxyapatite scaffolds

NASA Astrophysics Data System (ADS)

Shu, Yutian

Physiological bone tissue is a mineral/collagen composite with a hierarchical structure. The features in bone, such as mineral crystals, fibers, and pores can range from the nanometer to the centimeter in size. Currently available bone tissue scaffolds primarily address the chemical composition, pore size, and pore size distribution. While these design parameters are extensively investigated for mimicking bone function and inducing bone regeneration, little is known about microcracks, which is a prevalent feature found in fractured bone in vivo and associated with fracture healing and repair. Since the purpose of bone tissue engineering scaffold is to enhance bone regeneration, the coincidence of microcracks and bone densification should not be neglected but rather be considered as a potential parameter in bone tissue engineering scaffold design. The purpose of this study is to test the hypothesis that microcracks enhance bone healing. In vitro studies were designed to investigate the osteoblast (bone forming cells) response to microcracks in dense (94%) hydroxyapatite substrates. Microcracks were introduced using a well-established Vickers indentation technique. The results of our study showed that microcracks induced osteoblast alignment, enhanced osteoblast attachment and more rapid maturation. These findings may provide insight into fracture healing mechanism(s) as well as improve the design of bone tissue engineering orthopedic scaffolds for more rapid bone regeneration.

Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

PubMed Central

Yu, De-Gang; Nie, Shao-Bo; Liu, Feng-Xiang; Wu, Chuan-Long; Tian, Bo; Wang, Wen-Gang; Wang, Xiao-Qing; Zhu, Zhen-An; Mao, Yuan-Qing

2015-01-01

Background: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA). However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. Methods: A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD), mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. Results: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks). The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. Conclusion: The microarchitecture, mineralization and mechanical properties of subchondral bone changed in a time-dependent manner as OA progressed. PMID:26521785

Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis

PubMed Central

Yang, Y.; Lin, S.; Wang, B.; Gu, W.

2017-01-01

Objectives Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023. PMID:28634158

Carbon Nanoparticle Enhance Photoacoustic Imaging and Therapy for Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Talukdar, Yahfi

Healing critical sized bone defects has been a challenge that led to innovations in tissue engineering scaffolds and biomechanical stimulations that enhance tissue regeneration. Carbon nanocomposite scaffolds have gained interest due to their enhanced mechanical properties. However, these scaffolds are only osteoconductive and not osteoinductive. Stimulating regeneration of bone tissue, osteoinductivity, has therefore been a subject of intense research. We propose the use of carbon nanoparticle enhanced photoacoustic (PA) stimulation to promote and enhance tissue regeneration in bone tissue-engineering scaffolds. In this study we test the feasibility of using carbon nanoparticles and PA for in vivo tissue engineering applications. To this end, we investigate 1) the effect of carbon nanoparticles, such as graphene oxide nanoplatelets (GONP), graphene oxide nano ribbons (GONR) and graphene nano onions (GNO), in vitro on mesenchymal stem cells (MSC), which are crucial for bone regeneration; 2) the use of PA imaging to detect and monitor tissue engineering scaffolds in vivo; and 3) we demonstrate the potential of carbon nanoparticle enhanced PA stimulation to promote tissue regeneration and healing in an in vivo rat fracture model. The results from these studies demonstrate that carbon nanoparticles such as GNOP, GONR and GNO do not affect viability or differentiation of MSCs and could potentially be used in vivo for tissue engineering applications. Furthermore, PA imaging can be used to detect and longitudinally monitor subcutaneously implanted carbon nanotubes incorporated polymeric nanocomposites in vivo. Oxygen saturation data from PA imaging could also be used as an indicator for tissue regeneration within the scaffolds. Lastly, we demonstrate that daily stimulation with carbon nanoparticle enhanced PA increases bone fracture healing. Rats stimulated for 10 minutes daily for two weeks showed 3 times higher new cortical bone BV/TV and 1.8 times bone mineral density, compared to non-stimulated controls. The results taken together indicate that carbon nanoparticle enhanced PA stimulation serves as an anabolic stimulus for bone regeneration. The results suggest opportunities towards the development of implant device combination therapies for bone loss due to disease or trauma.

Normal spinal bone marrow in adults: dynamic gadolinium-enhanced MR imaging.

PubMed

Montazel, Jean-Luc; Divine, Marine; Lepage, Eric; Kobeiter, Hicham; Breil, Stephane; Rahmouni, Alain

2003-12-01

To determine the patterns of dynamic enhancement of normal spinal bone marrow in adults at gadolinium-enhanced magnetic resonance (MR) imaging and the changes that occur with aging. Dynamic contrast material-enhanced MR imaging of the thoracolumbar spine was performed in 71 patients. The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from bone marrow enhancement time curves (ETCs). The bone marrow signal intensity on T1-weighted spin-echo MR images was qualitatively classified into three grade categories. Quantitative ETC values were correlated with patient age and bone marrow fat content grade. Statistical analysis included mean t test comparison, analysis of variance, and regression analysis of the correlations between age and quantitative MR parameters. Emax, slope, and washout varied widely among the patients. Emax values were obtained within 1 minute after contrast material injection and ranged from 0% to 430%. Emax values were significantly higher in patients younger than 40 years than in those aged 40 years or older (P <.001). These values decreased with increasing age in a logarithmic relationship (r = 0.71). Emax values decreased as fat content increased, but some overlap among the fat content grades was noted. Analysis of variance revealed that Emax was significantly related to age (younger than 40 years vs 40 years or older) (P <.001) and fat content grade (P <.001) but not significantly related to sex. Dynamic contrast-enhanced MR imaging patterns of normal spinal bone marrow are dependent mainly on patient age and fat content.

Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.

PubMed

Rustom, Laurence E; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W; Lu, Yan; Markel, Mark D; Picart, Catherine; Wagoner Johnson, Amy J

2016-10-15

The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF‾, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF‾, of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. The increasing demand for bone repair calls for more efficacious bone scaffolds and calcium phosphate-based materials are considered suitable for this application. Macropores (>100μm) are necessary for bone ingrowth and vascularization. However, studies have shown that microporosity (<20μm) also enhances growth, but there is no consensus on the controlling mechanisms. In previous in vitro work, we suggested that micropore-induced capillarity had the potential to enhance bone growth in vivo. This work illustrates the positive effects of capillarity on bone regeneration in vivo; it demonstrates that micropore-induced capillarity significantly enhances the bone distribution in the scaffold. The results will impact the design of scaffolds to better exploit capillarity and improve treatments for large and load-bearing bone defects. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method.

PubMed

Yang, Xu; Tang, Songyuan; Tasciotti, Ennio; Righetti, Raffaella

2018-01-17

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat 'brighter' than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface. In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Recent advances in gene-enhanced bone tissue engineering.

PubMed

Betz, Volker M; Kochanek, Stefan; Rammelt, Stefan; Müller, Peter E; Betz, Oliver B; Messmer, Carolin

2018-03-30

The loss of bone tissue represents a critical clinical condition that is frequently faced by surgeons. Substantial progress has been made in the area of bone research, providing insight into the biology of bone under physiological and pathological conditions, as well as tools for the stimulation of bone regeneration. The present review discusses recent advances in the field of gene-enhanced bone tissue engineering. Gene transfer strategies have emerged as highly effective tissue engineering approaches for supporting the repair of the musculoskeletal system. By contrast to treatment with recombinant proteins, genetically engineered cells can release growth factors at the site of injury over extended periods of time. Of particular interest are the expedited technologies that can be applied during a single surgical procedure in a cost-effective manner, allowing translation from bench to bedside. Several promising methods based on the intra-operative genetic manipulation of autologous cells or tissue fragments have been developed in preclinical studies. Moreover, gene therapy for bone regeneration has entered the clinical stage with clinical trials for the repair of alveolar bone. Current trends in gene-enhanced bone engineering are also discussed with respect to the movement of the field towards expedited, translational approaches. It is possible that gene-enhanced bone tissue engineering will become a clinical reality within the next few years. Copyright © 2018 John Wiley & Sons, Ltd.

Bone surface enhancement in ultrasound images using a new Doppler-based acquisition/processing method

NASA Astrophysics Data System (ADS)

Yang, Xu; Tang, Songyuan; Tasciotti, Ennio; Righetti, Raffaella

2018-01-01

Ultrasound (US) imaging has long been considered as a potential aid in orthopedic surgeries. US technologies are safe, portable and do not use radiations. This would make them a desirable tool for real-time assessment of fractures and to monitor fracture healing. However, image quality of US imaging methods in bone applications is limited by speckle, attenuation, shadow, multiple reflections and other imaging artifacts. While bone surfaces typically appear in US images as somewhat ‘brighter’ than soft tissue, they are often not easily distinguishable from the surrounding tissue. Therefore, US imaging methods aimed at segmenting bone surfaces need enhancement in image contrast prior to segmentation to improve the quality of the detected bone surface. In this paper, we present a novel acquisition/processing technique for bone surface enhancement in US images. Inspired by elastography and Doppler imaging methods, this technique takes advantage of the difference between the mechanical and acoustic properties of bones and those of soft tissues to make the bone surface more easily distinguishable in US images. The objective of this technique is to facilitate US-based bone segmentation methods and improve the accuracy of their outcomes. The newly proposed technique is tested both in in vitro and in vivo experiments. The results of these preliminary experiments suggest that the use of the proposed technique has the potential to significantly enhance the detectability of bone surfaces in noisy ultrasound images.

Phase-Resolved Spectroscopy of the Low-Mass X-ray Binary V801 Ara

NASA Astrophysics Data System (ADS)

Brauer, Kaley; Vrtilek, Saeqa Dil; Peris, Charith; McCollough, Michael

2018-06-01

We present phase-resolved optical spectra of the low mass X-ray binary system V801 Ara. The spectra, obtained in 2014 with IMACS on the Magellan/Baade telescope at Las Campanas Observatory, cover the full binary orbit of 3.8 hours. They contain strong emission features allowing us to map the emission of Hα, Hβ, He II λ4686, and the Bowen blend at λ4640. The radial velocity curves of the Bowen blend shows significantly stronger modulation at the orbital period than Hα as expected for the former originating on the secondary with the latter consistent with emission dominated by the disk. Our tomograms of Hα and Hβ are the most detailed studies of these lines for V801 to date and they clearly detect the accretion disk. The Hβ emission extends to higher velocities than Hα, suggesting emission from closer to the neutron star and differentiating temperature variance in the accretion disk for the first time. The center of the accretion disk appears offset from the center-of-mass of the neutron star as has been seen in several other X-ray binaries. This is often interpreted to imply disk eccentricity. Our tomograms do not show strong evidence for a hot spot at the point where the accretion stream hits the disk. This could imply a reduced accretion rate or could be due to the spot being drowned out by bright accretion flow around it. There is enhanced emission further along the disk, however, which implies gas stream interaction downstream of the hot spot.

RECONCILING AGN-STAR FORMATION, THE SOLTAN ARGUMENT, AND MEIER’S PARADOX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garofalo, David; Kim, Matthew I.; Christian, Damian J.

2016-02-01

We provide a theoretical context for understanding the recent work of Kalfountzou et al. showing that star formation is enhanced at lower optical luminosity in radio-loud quasars. Our proposal for coupling the assumption of collimated FRII quasar-jet-induced star formation with lower accretion optical luminosity also explains the observed jet power peak in active galaxies at higher redshift compared to the peak in accretion power, doing so in a way that predicts the existence of a family of radio-quiet active galactic nuclei associated with rapidly spinning supermassive black holes at low redshift, as mounting observations suggest. The relevance of this work liesmore » in its promise to explain the observed cosmological evolution of accretion power, jet power, and star formation in a way that is both compatible with the Soltan argument and resolves the so-called “Meier Paradox.”.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guha, A.; Prasad, G.C.; Udupa, K.N.

Scintillography and autoradiography were used to study the healing of humeral fractures in rats injected with Sr/sup 85/. Among various agents studied for an influence on the rate of fracture healing, the total extract of the herb Cissus quadrangularis was tested. In both controls and animals receiving C. quadrangularis extract there was demineralization of the fractured bone at the site of fracture. In the treated group, there was a somewhat earlier rise in Sr/ sup 85/ uptake just after the first injection. Thereafter, uptake again became high, similar to the control samples from the 6th day onward. The maximum uptakemore » of control bone was found to be around the 19th day after fracturing, while in the treated group, maximum uptake was on 15th day. Though there was a minor difference in the period of maximum uptake between treated and control bone, the rate of uptake in the treated sample was markedly higher than that of the control sample. The fall of Sr/sup 85/ uptake in the treated bone was very rapid, whereas in the untreated animals it was more gradual. All these findings on the uptake of Sr/sup 85/ as measured by a G-M counter, corroborated x-ray pictures and gross autoradiography at different stages of fracture healing. The radiological and autoradiographic findings also clearly showed that the healing in the treated group was quicker than in the controls. Furthermore, the callus in the treated animals underwent remodeling processes much earlier than in the nontreated ones. It is concluded that if the uptake of Sr in the treated andimals is greater thand in the control samples at the site of fracture, healing activity is more pronounced. However, studies on patients have shown that the uptake of Sr/sup 85/ alone in the fractured region may not give an accurate picture of the healing processes. Thus, at the end of first week after fractures, accretion rate of Ca reached a peak and thereafter remained higher than normal throughout the period of healing. But when these results were compared with x-ray pictures, it was observed that the accretion rate in poorly uniting fractures did not diifer from that of normally healing fractures, so that in interpreting the rate of healing by the uptake of Sr/sup 85/, radiography is also required to make the correct assessment of the status of fracture healing. The Sr/sup 85/ uptake curves show that the uptake pattern can be divided into three definite phases. ln the first phase, which lasts for six days, there is and enormous amount of decalcification from the broken fragments of bone possibly due to increased vascularity of the region, and also to the increased accumulation of mucopolysaccharides locally. In the second phase, which lasts for another 8 to 12 days, rapid increase in the accretion of Ca as evidenced by increase in the uptake of Sr/sup 85/ noted. During the 2nd phase, histologic studies indicated that large amounts of collagen fibers appear, which possibly combine with all the available Ca salts there. The third phase shows a rapid fall of Sr/sup 85/ uptake, indicating that the callus formed in the second phase is rapidly being remodeled. (BBB)« less

Proceedings of the Airframe Icing Workshop

NASA Technical Reports Server (NTRS)

Colantonio, Ron O. (Editor)

2009-01-01

The NASA Glenn Research Center (GRC) has a long history of working with its partners towards the understanding of ice accretion formation and its associated degradation of aerodynamic performance. The June 9, 2009, Airframe Icing Workshop held at GRC provided an opportunity to examine the current NASA airframe icing research program and to dialogue on remaining and emerging airframe icing issues and research with the external community. Some of the airframe icing gaps identified included, but are not limited to, ice accretion simulation enhancements, three-dimensional benchmark icing database development, three-dimensional iced aerodynamics modeling, and technology development for a smart icing system.

Parathyroid hormone related to bone regeneration in grafted and nongrafted tooth extraction sockets in rats.

PubMed

Kuroshima, Shinichiro; Al-Salihi, Zeina; Yamashita, Junro

2013-02-01

The quality and quantity of bone formed in tooth extraction sockets impact implant therapy. Therefore, the establishment of a new approach to enhance bone formation and to minimize bone resorption is important for the success of implant therapy. In this study, we investigated whether intermittent parathyroid hormone (PTH) therapy enhanced bone formation in grafted sockets. Tooth extractions of the maxillary first molars were performed in rats, and the sockets were grafted with xenograft. Intermittent PTH was administered either for 7 days before extractions, for 14 days after extractions, or both. The effect of PTH therapy on bone formation in the grafted sockets was assessed using microcomputed tomography at 14 days after extractions. PTH therapy for 7 days before extractions was not effective to augment bone fill, whereas PTH therapy for 14 days after operation significantly augmented bone formation in the grafted sockets. Intermittent PTH therapy starting right after tooth extractions significantly enhanced bone fill in the grafted sockets, suggesting that PTH therapy can be a strong asset for the success of the ridge preservation procedure.

Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.

PubMed

Lee, Su-Ui; Park, Sang-Joon; Kwak, Han Bok; Oh, Jaemin; Min, Yong Ki; Kim, Seong Hwan

2008-01-01

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone mass and improve bone architecture. In this study, we demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances differentiation and mineralization of osteoblasts in vitro. We found that ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs), inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid in the late stage of osteoblast differentiation. Importantly, ursolic acid was shown to have bone-forming activity in vivo in a mouse calvarial bone formation model. A high proportion of positive immunostaining of BMP-2 was found in the nuclear region of woven bone formed by ursolic acid. These results suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation.

Modeling of surface roughness effects on glaze ice accretion

NASA Technical Reports Server (NTRS)

Hansman, R. John, Jr.; Yamaguchi, Keiko; Berkowitz, Brian M.; Potapczuk, Mark

1990-01-01

A series of experimental investigations focused on studying the cause and effect of roughness on accreting glaze ice surfaces were conducted. Detailed microvideo observations were made of glaze ice accretions on 1 to 4 inch diameter cylinders in three icing wind tunnels (the Data Products of New England six inch test facility, the NASA Lewis Icing Research Tunnel, and the B. F. Goodrich Ice Protection Research Facility). Infrared thermal video recordings were made of accreting ice surfaces in the Goodrich facility. Distinct zones of surface water behavior were observed; a smooth wet zone in the stagnation region with a uniform water film; a rough zone where surface tension effects caused coalescence of surface water into stationary beads; a horn zone where roughness elements grow into horn shapes; a runback zone where surface water ran back as rivulets; and a dry zone where rime feathers formed. The location of the transition from the smooth to the rough zone was found to migrate with time towards the stagnation point. The behavior of the transition appeared to be controlled by boundary layer transition and bead formation mechanisms at the interface between the smooth and rough zones. Regions of wet ice growth and enhanced heat transfer were clearly visible in the infrared video recordings of glaze ice surfaces. A simple multi-zone modification to the current glaze ice accretion model was proposed to include spatial variability in surface roughness.

Reduced modeling of the magnetorotational instability

NASA Astrophysics Data System (ADS)

Jamroz, Ben F.

2009-06-01

Accretion describes the process by which matter in an astrophysical disk falls onto a central massive object. Accretion disks are present in many astrophysical situations including binary star systems, young stellar objects, and near black holes at the center of galaxies. Measurements from observations of these disks have shown that viscous processes are unable to transport the necessary levels of angular momentum needed for accretion. Therefore, accretion requires an efficient mechanism of angular momentum transport. Mixing by turbulent processes greatly enhances the level of angular momentum transport in a turbulent fluid. Thus, the generation of turbulence in these disks may provide the mechanism needed for accretion. A classical result of hydrodynamic theory is that typical accretion disks are hydrodynamically stable to shear instabilities, since the specific angular momentum increases outwards. Other processes of generating hydrodynamic turbulence (barotropic instability, baroclinic instability, sound wave, shock waves, finite amplitude instabilities) may be present in these disks, however, none of these mechanisms has been shown to produce the level of angular momentum transport needed for accretion. Hydrodynamical turbulence does not produce enough angular momentum transport to produce the level of accretion observed in astrophysical accretion disks. The leading candidate for the source of turbulence leading to the transport of angular momentum is the magnetorotational instability, a linear axisymmetric instability of electrically conducting fluid in the presence of an imposed magnetic field and shear (or differential rotation). This instability is an efficient mechanism of angular momentum transport generating the level of transport needed for accretion. The level of effective angular momentum transport is determined by the saturated state of sustained turbulence generated by the instability. The mechanism of nonlinear saturation of this instability is not well understood. Many recent numerical investigations of this problem are performed in a local domain, where the global cylindrical background state is projected onto a local Cartesian domain. The resulting system is then numerically modeled within a "shearing box" framework to obtain estimates of angular momentum transport and therefore accretion. However, the simplified geometry of the local domain, and the projection of global quantities leads to a model where the instability is able to grow unboundedly. Utilizing disparate characteristic scales, this thesis presents a reduced asymptotic model for the magnetorotational instability that allows a large scale feedback of local stresses (Reynolds, Maxwell and mixed) onto the projected background state. This system is investigated numerically to determine the impact of allowing this feedback on the saturated level of angular momentum transport.

Impact of convection and resistivity on angular momentum transport in dwarf novae.

NASA Astrophysics Data System (ADS)

Scepi, N.; Lesur, G.; Dubus, G.; Flock, M.

2017-12-01

The eruptive cycles of dwarf novae are thought to be due to a thermal-viscous instability in the accretion disk surrounding the white dwarf. This model has long been known to imply enhanced angular momentum transport in the accretion disk during outburst. This is measured by the stress to pressure ratio α, with α≈ 0.1 required in outburst compared to α≈ 0.01 in quiescence. Such an enhancement in α has recently been observed in simulations of turbulent transport driven by the magneto-rotational instability (MRI) when convection is present, without requiring a net magnetic flux. We independently recover this result by carrying out PLUTO MHD simulations of vertically stratified, radiative, shearing boxes with the thermodynamics and opacities appropriate to dwarf novae. The results are robust against the choice of vertical boundary conditions. In the quiescent state, the disk is only very weakly ionized so, in the second part of our work, we studied the impact of resistive MHD on transport.We find that the MRI-driven transport is quenched (α≈ 0) below the critical density at which the magnetic Reynolds number R_{m}≤ 10^4. This is problematic because the X-ray emission observed in quiescent systems requires ongoing accretion onto the white dwarf.

Enhancement of the Accretion of Jupiters Core by a Voluminous Low-Mass Envelope

NASA Technical Reports Server (NTRS)

Lissauer, Jack J.; D'angelo, Gennaro; Weidenschilling, Stuart John; Bodenheimer, Peter; Hubickyj, Olenka

2013-01-01

We present calculations of the early stages of the formation of Jupiter via core nucleated accretion and gas capture. The core begins as a seed body of about 350 kilometers in radius and orbits in a swarm of planetesimals whose initial radii range from 15 meters to 100 kilometers. We follow the evolution of the swarm by accounting for growth and fragmentation, viscous and gravitational stirring, and for drag-induced migration and velocity damping. Gas capture by the core substantially enhances the cross-section of the planet for accretion of small planetesimals. The dust opacity within the atmosphere surrounding the planetary core is computed self-consistently, accounting for coagulation and sedimentation of dust particles released in the envelope as passing planetesimals are ablated. The calculation is carried out at an orbital semi-major axis of 5.2 AU and an initial solids' surface density of 10/g/cm^2 at that distance. The results give a core mass of 7 Earth masses and an envelope mass of approximately 0.1 Earth mass after 500,000 years, at which point the envelope growth rate surpasses that of the core. The same calculation without the envelope gives a core mass of only 4 Earth masses.

Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

PubMed

Nevins, Marc L; Said, Sherif

2017-12-28

Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels.

PubMed

Ho, Steve S; Vollmer, Nina L; Refaat, Motasem I; Jeon, Oju; Alsberg, Eben; Lee, Mark A; Leach, J Kent

2016-10-01

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

PubMed Central

Sheikh, Zeeshan; Javaid, Mohammad Ahmad; Hamdan, Nader; Hashmi, Raheel

2015-01-01

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration. PMID:28788032

Injectable Reactive Biocomposites For Bone Healing In Critical-Size Rabbit Calvarial Defects

DTIC Science & Technology

2012-03-29

defects (i.e. be conformable), provide temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of...temporary protection to the brain until the bone heals, and enhance tissue regeneration with the delivery of biologics. In this study, we evaluated the...complex defects (i.e. be conformable), harden to provide temporary protection until tissue remodels (i.e. be settable), and enhance tissue regeneration

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

Diapirs of the Mediterranean ridge: The tectonic regime of an incipient accreted terrane

NASA Technical Reports Server (NTRS)

Mart, Y.

1988-01-01

The occurrence of diapirs in the Mediterranean ridge stems mostly from the massive deposition of salt and gypsum in the Mediterranean basin during the late Miocean. The diapiric emplacement of the evaporitic sequence is not obvious, because the mobilization of the salt beds and the initiation of the diapiric upward flow are constrained by the relatively shallow thickness of the Plio-Pleistocene sedimentary overburden and by the low heat flow that prevails in the eastern Mediterranean. The diapirs consist also of early Cretaceous shales as well as other gravitationally metastable strata which are less mobile than salt. Studies of subduction trenches and their surroundings show that shallow ridges occur seaward of the trenches in many places. The collisional motion between the African and the Eurasian plates would further enhance accretion of sediments in the Mediterranean ridge, which would attain subaerial exposure, and eventually would become a mountain range accreted to southern Europe. The numerous diapirs of salt and shales that occur in the ridge would be common features in the future accreted terrane, indicating an intermediate extensional phase in the tectonic history of the development of crustal growth.

Extending Rest between Unloading Cycles Does Not Enhance Bone's Long-Term Recovery.

PubMed

Manske, Sarah L; Vijayaraghavan, Surabhi; Tuthill, Alyssa; Brutus, Olivier; Yang, Jie; Gupta, Shikha; Judex, Stefan

2015-10-01

Multiple exposures to unloading are overall more deleterious to the skeleton than is single exposure, although the rate of bone loss may diminish during multiple exposures. Here, we determined whether extending the reambulation (RA) period from 3 wk to 9 wk will mitigate bone loss during three distinct 3-wk hindlimb unloading (HLU) periods and enhance long-term recovery in skeletally mature, genetically heterogeneous mice. Female adult mice (4 months old) were subjected to three cycles of 3-wk unloading with 3-wk or 9-wk RA periods in between. Mice were terminated 46 wk after initiation of the study. Outcome measures for the distal femur were determined from multiple in vivo micro-computed tomography scans and finite-element modeling. Tripling RA duration enhanced trabecular bone recovery in between HLU periods but also increased the rate of loss of bone volume fraction (bone volume/tissue volume) and metaphyseal stiffness during subsequent HLU periods. With shorter RA periods, the magnitude of bone loss decreased by the second HLU period, whereas this decrease was delayed with longer RA periods. RA duration did not affect long-term recovery 46 wk after the start of the experimental protocol, as both HLU groups had similar levels of bone volume/tissue volume, cortical area, and stiffness. Individual cage activity levels were unrelated to the magnitude of bone loss during HLU or bone recovery during RA. These data suggest that extending recovery duration between periods of unloading may provide temporary benefits but is an ineffective long-term strategy for combating the devastation of trabecular morphology and mechanics, as temporarily enhanced recovery is largely cancelled out by greater susceptibility to unloading. They also emphasize that cortical bone is more amenable to long-term recovery than is trabecular bone.

Peripheral-specific y2 receptor knockdown protects mice from high-fat diet-induced obesity.

PubMed

Shi, Yan-Chuan; Lin, Shu; Castillo, Lesley; Aljanova, Aygul; Enriquez, Ronaldo F; Nguyen, Amy D; Baldock, Paul A; Zhang, Lei; Bijker, Martijn S; Macia, Laurence; Yulyaningsih, Ernie; Zhang, Hui; Lau, Jackie; Sainsbury, Amanda; Herzog, Herbert

2011-11-01

Y2 receptors, particularly those in the brain, have been implicated in neuropeptide Y (NPY)-mediated effects on energy homeostasis and bone mass. Recent evidence also indicates a role for Y2 receptors in peripheral tissues in this process by promoting adipose tissue accretion; however their effects on energy balance remain unclear. Here, we show that adult-onset conditional knockdown of Y2 receptors predominantly in peripheral tissues results in protection against diet-induced obesity accompanied by significantly reduced weight gain, marked reduction in adiposity and improvements in glucose tolerance without any adverse effect on lean mass or bone. These changes occur in association with significant increases in energy expenditure, respiratory exchange ratio, and physical activity and despite concurrent hyperphagia. On a chow diet, knockdown of peripheral Y2 receptors results in increased respiratory exchange ratio and physical activity with no effect on lean or bone mass, but decreases energy expenditure without effecting body weight or food intake. These results suggest that peripheral Y2 receptor signaling is critical in the regulation of oxidative fuel selection and physical activity and protects against the diet-induced obesity. The lack of effects on bone mass seen in this model further indicates that bone mass is primarily controlled by non-peripheral Y2 receptors. This study provides evidence that novel drugs that target peripheral rather than central Y2 receptors could provide benefits for the treatment of obesity and glucose intolerance without adverse effects on lean and bone mass, with the additional benefit of avoiding side effects often associated with pharmaceuticals that act on the central nervous system.

Measurement accuracy and perceived quality of imaging systems for the evaluation of periodontal structures.

PubMed

Baksi, B Güniz

2008-07-01

The aim of this study was to compare the subjective diagnostic quality of F-speed film images and original and enhanced storage phosphor plate (SPP) digital images for the visualization of periodontal ligament space (PLS) and periapical (PB) and alveolar crestal bone (CB) and to assess the accuracy of these image modalities for the measurement of alveolar bone levels. Standardized images of six dried mandibles were obtained with film and Digora SPPs. Six evaluators rated the visibility of anatomical structures using a three-point scale. Alveolar bone levels were measured from the coronal-most tip of the marginal bone to a reference point. Results were compared by using Friedman and Wilcoxon signed-ranks tests. The kappa (kappa) statistic was used to measure agreement among observers. The measurements were compared using repeated measures analysis of variance and Bonferroni tests (P = 0.05). A paired t test was used for comparison with true bone levels (P = 0.05). Enhanced SPP images were rated superior, followed by film and then the original SPP images, for the evaluation of anatomical structures. The value of kappa rose from fair to substantial after the enhancement of the SPP images. Film and enhanced SPP images provided alveolar bone lengths close to the true bone lengths. Enhancement of digital images provided better visibility and resulted in comparable accuracy to film images for the evaluation of periodontal structures.

Lithium chloride enhances bone regeneration and implant osseointegration in osteoporotic conditions.

PubMed

Jin, Yifan; Xu, Lihua; Hu, Xiaohui; Liao, Shixian; Pathak, Janak L; Liu, Jinsong

2016-10-06

Osteoporotic patients have a high risk of dental and orthopedic implant failure. Lithium chloride (LiCl) has been reported to enhance bone formation. However, the role of LiCl in the success rate of dental and orthopedic implants in osteoporotic conditions is still unknown. We investigated whether LiCl enhances implant osseointegration, implant fixation, and bone formation in osteoporotic conditions. Sprague-Dawley female rats (n = 18) were ovariectomized (OVX) to induce osteoporosis, and another nine rats underwent sham surgery. Three months after surgery, titanium implants were implanted in the tibia of the OVX and sham group rats. After implantation, the OVX rats were gavaged with 150 mg/kg/2 days of LiCl (OVX + LiCl group) or saline (OVX group), and sham group rats were gavaged with saline for 3 months. Implant osseointegration and bone formation were analyzed using histology, biomechanical testing, and micro computed tomography (micro-CT). More bone loss was observed in the OVX group compared to the control, and LiCl treatment enhanced bone formation and implant fixation in osteoporotic rats. In the OVX group, bone-implant contact (BIC) was decreased by 81.2 % compared to the sham group. Interestingly, the OVX + LiCl group showed 4.4-fold higher BIC compared to the OVX group. Micro-CT data of tibia from the OVX + LiCl group showed higher bone volume, trabecular thickness, trabecular number, and osseointegration compared to the OVX group. Maximum push-out force and implant-bone interface shear strength were 2.9-fold stronger in the OVX + LiCl group compared to the OVX group. In conclusion, LiCl enhanced implant osseointegration, implant fixation, and bone formation in osteoporotic conditions, suggesting LiCl as a promising therapeutic agent to prevent implant failure and bone loss in osteoporotic conditions.

Effects of hot boning and moisture enhancement on the eating quality of cull cow beef.

PubMed

Pivotto, L M; Campbell, C P; Swanson, K; Mandell, I B

2014-01-01

The effects of chilling method and moisture enhancement were examined for improving eating quality of semimembranosus (SM) and longissimus lumborum (LL) from 62 cull beef cows. Chilling method included hot boning muscles after 45 to 60 min postmortem or conventional chilling for 24 h. Moisture enhancement included 1) a non-injected control (CONT) or injection processing (10% of product weight) using 2) Sodium Tripolyphosphate/salt (Na/STP), 3) Sodium Citrate (NaCIT), 4) Calcium Ascorbate (CaASC), or 5) Citrus Juices (CITRUS). Chilling method by moisture enhancement treatment interactions (P<0.09) were due to decreased hue, chroma and sarcomere length values in hot boned vs. conventionally chilled product (SM and LL) for CaASC vs. other moisture enhancement treatments. Chilling method by moisture enhancement treatment interactions (P<0.05) were due to decreased shear force and increased tenderness in conventionally chilled vs. hot boned LL using CaASC vs. Na/STP. Moisture enhancement can improve tenderness of cull cow beef depending on combinations of chilling method and moisture enhancement treatments used. © 2013.

Screening of Osteogenic-Enhancing Short Peptides from BMPs for Biomimetic Material Applications

PubMed Central

Kanie, Kei; Kurimoto, Rio; Tian, Jing; Ebisawa, Katsumi; Narita, Yuji; Honda, Hiroyuki; Kato, Ryuji

2016-01-01

Bone regeneration is an important issue in many situations, such as bone fracture and surgery. Umbilical cord mesenchymal stem cells (UC-MSCs) are promising cell sources for bone regeneration. Bone morphogenetic proteins and their bioactive peptides are biomolecules known to enhance the osteogenic differentiation of MSCs. However, fibrosis can arise during the development of implantable biomaterials. Therefore, it is important to control cell organization by enhancing osteogenic proliferation and differentiation and inhibiting fibroblast proliferation. Thus, we focused on the screening of such osteogenic-enhancing peptides. In the present study, we developed new peptide array screening platforms to evaluate cell proliferation and alkaline phosphatase activity in osteoblasts, UC-MSCs and fibroblasts. The conditions for the screening platform were first defined using UC-MSCs and an osteogenic differentiation peptide known as W9. Next, in silico screening to define the candidate peptides was carried out to evaluate the homology of 19 bone morphogenetic proteins. Twenty-five candidate 9-mer peptides were selected for screening. Finally, the screening of osteogenic-enhancing (osteogenic cell-selective proliferation and osteogenic differentiation) short peptide was carried out using the peptide array method, and three osteogenic-enhancing peptides were identified, confirming the validity of this screening. PMID:28773850

Magnetospheric Accretion in Close Pre-main-sequence Binaries

NASA Astrophysics Data System (ADS)

Ardila, David R.; Jonhs-Krull, Christopher; Herczeg, Gregory J.; Mathieu, Robert D.; Quijano-Vodniza, Alberto

2015-10-01

The transfer of matter between a circumbinary disk and a young binary system remains poorly understood, obscuring the interpretation of accretion indicators. To explore the behavior of these indicators in multiple systems, we have performed the first systematic time-domain study of young binaries in the ultraviolet. We obtained far- and near-ultraviolet HST/COS spectra of the young spectroscopic binaries DQ Tau and UZ Tau E. Here we focus on the continuum from 2800 to 3200 Å and on the C iv doublet (λλ1548.19, 1550.77 Å) as accretion diagnostics. Each system was observed over three or four consecutive binary orbits, at phases ∼0, 0.2, 0.5, and 0.7. Those observations are complemented by ground-based U-band measurements. Contrary to model predictions, we do not detect any clear correlation between accretion luminosity and phase. Further, we do not detect any correlation between C iv flux and phase. For both stars the appearance of the C iv line is similar to that of single Classical T Tauri Stars (CTTSs), despite the lack of stable long-lived circumstellar disks. However, unlike the case in single CTTSs, the narrow and broad components of the C iv lines are uncorrelated, and we argue that the narrow component is powered by processes other than accretion, such as flares in the stellar magnetospheres and/or enhanced activity in the upper atmosphere. We find that both stars contribute equally to the narrow component C iv flux in DQ Tau, but the primary dominates the narrow component C iv emission in UZ Tau E. The C iv broad component flux is correlated with other accretion indicators, suggesting an accretion origin. However, the line is blueshifted, which is inconsistent with its origin in an infall flow close to the star. It is possible that the complicated geometry of the region, as well as turbulence in the shock region, are responsible for the blueshifted line profiles.

Bone Regeneration in Critical Bone Defects Using Three-Dimensionally Printed β-Tricalcium Phosphate/Hydroxyapatite Scaffolds Is Enhanced by Coating Scaffolds with Either Dipyridamole or BMP-2

PubMed Central

Ishack, Stephanie; Mediero, Aranzazu; Wilder, Tuere; Ricci, John L.; Cronstein, Bruce N.

2017-01-01

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3-D) printing technology we have created custom 3-D scaffolds of hydroxyapatite (HA)/Beta-Tri-Calcium Phosphate (β-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. 15% HA:85% β-TCP scaffolds were designed using Robocad software, fabricated using a 3-D Robocasting system, and sintered at 1100°C for 4h. Scaffolds were coated with BMP-2 (200ng/ml), Dypiridamole 100µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/β-TCP- dipyridamole and HA/β-TCP -BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4 and 8 weeks (n=5 per group; p≤ 0.05, p≤ 0.05 and p≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/β-TCP- dipyridamole and HA/β-TCP-BMP-2 scaffolds. coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/β-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. PMID:26513656

Sclerostin-neutralizing Antibody Enhances Bone Regeneration around Oral Implants.

PubMed

Yu, Shan Huey; Hao, Jie; Fretwurst, Tobias; Liu, Min; Kostenuik, Paul; Giannobile, William V; Jin, Qiming

2018-06-19

Dental implants have been an important option for the replacement of missing teeth. A major clinical challenge is how best to accelerate bone regeneration and reduce the healing time for functional restoration after implant placement. Monoclonal antibody against sclerostin (Scl-Ab) has been shown to enhance alveolar bone formation and fracture repair. The aim of this study was to investigate the effects of systemic administration of Scl-Ab on dental implant osseointegration and bone regeneration in an experimental alveolar ridge tooth extraction model. To investigate the effects of Scl-Ab on bone regeneration and dental implant osseointegration, an experimental alveolar bone osteotomy rat model was adopted. One month after the extraction of maxillary right first molars, osteotomy defects were created at the coronal aspect of each of the extraction sites, and 1x2 mm custom titanium implants were pressed-fitted into the osteotomies. Coincident with initial implant placement, Scl-Ab or vehicle was administered subcutaneously twice weekly at a dose of 25 mg/kg for 10-28 days and compared to a vehicle control. Rats were sacrificed 10, 14 and 28d after surgery, and maxillae were harvested and analyzed by micro-computed tomography (microCT), histology and histomorphometry. MicroCT analysis demonstrated that maxillary bone volume fraction was approximately 2 to 2.5-fold greater in Scl-Ab treated animals as compared to vehicle alone at days 14 and 28. Consistent with those findings, 2-D bone fill percentage within the coronal osteotomy sites were highest in Scl-Ab treatment groups at 28d. In addition, bone-implant contact at 28d was approximately 2-fold greater in the Scl-Ab group compared to vehicle controls. These results indicate that systemic Scl-Ab administration enhances osseointegration and bone regeneration around dental implants. This approach offers potential as a treatment modality for patients with low bone mass or bone defects to achieve more predictable bone regeneration at alveolar bone defects, and to enhance dental implant osseointegration.

The prospective opportunities offered by magnetic scaffolds for bone tissue engineering: a review

PubMed Central

ORTOLANI, ALESSANDRO; BIANCHI, MICHELE; MOSCA, MASSIMILIANO; CARAVELLI, SILVIO; FUIANO, MARIO; MARCACCI, MAURILIO; RUSSO, ALESSANDRO

2016-01-01

Magnetic scaffolds are becoming increasingly attractive in tissue engineering, due to their ability to enhance bone tissue formation by attracting soluble factors, such as growth factors, hormones and polypeptides, directly to the implantation site, as well as their potential to improve the fixation and stability of the implant. Moreover, there is increasing evidence that the synergistic effects of magnetic scaffolds and magnetic fields can promote bone repair and regeneration. In this manuscript we review the recent innovations in bone tissue engineering that exploit magnetic biomaterials combined with static magnetic fields to enhance bone cell adhesion and proliferation, and thus bone tissue growth. PMID:28217659

Dose in bone and tissue near bone-tissue interface from electron beam.

PubMed

Shiu, A S; Hogstrom, K R

1991-08-01

This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for clinical judgment when electron beams are used to treat lesions behind bone or near bony structures. We feel these data enhance the ability to recognize the shortcomings of the current dose calculation algorithm used clinically.

Contribution of recent hurricanes to wetland sedimentation in coastal Louisiana

NASA Astrophysics Data System (ADS)

Liu, Kam-biu; Bianchette, Thomas; Zou, Lei; Qiang, Yi; Lam, Nina

2017-04-01

Hurricanes are important agents of sediment deposition in the wetlands of coastal Louisiana. Since Hurricanes Katrina and Rita of 2005, coastal Louisiana has been impacted by Hurricanes Gustav (2008), Ike (2008), and Isaac (2012). By employing the principles and methods of paleotempestology we have identified the storm deposits attributed to the three most recent hurricanes in several coastal lakes and swamps in Louisiana. However, the spatial distribution and volume of these storm depositions cannot be easily inferred from stratigraphic data derived from a few locations. Here we report on results from a GIS study to analyze the spatial and temporal patterns of storm deposition based on data extracted from the voluminous CRMS (Coastal Reference Monitoring System) database, which contains vertical accretion rate measurements obtained from 390 wetland sites over various time intervals during the past decade. Wetland accretion rates averaged about 2.89 cm/yr from stations sampled before Hurricane Isaac, 4.04 cm/yr during the 7-month period encompassing Isaac, and 2.38 cm/yr from sites established and sampled after Isaac. Generally, the wetland accretion rates attributable to the Isaac effects were 40% and 70% greater than before and after the event, respectively. Accretion rates associated with Isaac were highest at wetland sites along the Mississippi River and its tributaries instead of along the path of the hurricane, suggesting that freshwater flooding from fluvial channels, enhanced by the storm surge from the sea, is the main mechanism responsible for increased accretion in the wetlands. Our GIS work has recently been expanded to include other recent hurricanes. Preliminary results indicate that, for non-storm periods, the average wetland accretion rates between Katrina/Rita and Gustav/Ike was 2.58 cm/yr; that between Gustav/Ike and Isaac was 1.95 cm/yr; and that after Isaac was 2.37 cm/yr. In contrast, the accretion rates attributable to the effects of Gustav/Ike and Isaac were 4.41 cm/yr and 3.52 cm/yr, respectively. These results show that hurricane-related accretion rates in wetlands are 50 - 225% higher than the normal rates typical of non-storm periods.

Spherical accretion in giant elliptical galaxies: multi-transonicity, shocks, and implications on AGN feedback

NASA Astrophysics Data System (ADS)

Raychaudhuri, Sananda; Ghosh, Shubhrangshu; Joarder, Partha S.

2018-06-01

Isolated massive elliptical galaxies, or that are present at the center of cool-core clusters, are believed to be powered by hot gas accretion directly from their surrounding hot X-ray emitting gaseous medium. This leads to a giant Bondi-type spherical/quasi-spherical accretion flow onto their host SMBHs, with the accretion flow region extending well beyond the Bondi radius. In this work, we present a detailed study of Bondi-type spherical flow in the context of these massive ellipticals by incorporating the effect of entire gravitational potential of the host galaxy in the presence of cosmological constant Λ, considering a five-component galactic system (SMBH + stellar + dark matter + hot gas + Λ). The current work is an extension of Ghosh & Banik (2015), who studied only the cosmological aspect of the problem. The galactic contribution to the potential renders the (adiabatic) spherical flow to become multi-transonic in nature, with the flow topology and flow structure significantly deviating from that of classical Bondi solution. More notably, corresponding to moderate to higher values of galactic mass-to-light ratios, we obtain Rankine-Hugoniot shocks in spherical wind flows. Galactic potential enhances the Bondi accretion rate. Our study reveals that there is a strict lower limit of ambient temperature below which no Bondi accretion can be triggered; which is as high as ˜9 × 106 K for flows from hot ISM-phase, indicating that the hot phase tightly regulates the fueling of host nucleus. Our findings may have wider implications, particularly in the context of outflow/jet dynamics, and radio-AGN feedback, associated with these massive galaxies in the contemporary Universe.

Effects of Fallback Accretion on Protomagnetar Outflows in Gamma-Ray Bursts and Superluminous Supernovae

NASA Astrophysics Data System (ADS)

Metzger, Brian D.; Beniamini, Paz; Giannios, Dimitrios

2018-04-01

Rapidly spinning, strongly magnetized protoneutron stars (“millisecond protomagnetars”) are candidate central engines of long-duration gamma-ray bursts (GRBs), superluminous supernovae (SLSNe), and binary neutron star mergers. Magnetar birth may be accompanied by the fallback of stellar debris, lasting for seconds or longer following the explosion. Accretion alters the magnetar evolution by (1) providing an additional source of rotational energy (or a potential sink, if the propeller mechanism operates), (2) enhancing the spin-down luminosity above the dipole rate by compressing the magnetosphere and expanding the polar cap region of open magnetic field lines, and (3) supplying an additional accretion-powered neutrino luminosity that sustains the wind baryon loading, even after the magnetar’s internal neutrino luminosity has subsided. The more complex evolution of the jet power and magnetization of an accreting magnetar more readily accounts for the high 56Ni yields of GRB SNe and the irregular time evolution of some GRB light curves (e.g., bursts with precursors followed by a long quiescent interval before the main emission episode). Additional baryon loading from accretion-powered neutrino irradiation of the polar cap lengthens the time frame over which the jet magnetization is in the requisite range σ ≲ 103 for efficient gamma-ray emission, thereby accommodating GRBs with ultralong durations. Though accretion does not significantly raise the maximum energy budget from the limit of ≲ few × 1052 erg for an isolated magnetar, it greatly expands the range of magnetic field strengths and birth spin periods capable of powering GRB jets, reducing the differences between the magnetar properties normally invoked to explain GRBs versus SLSNe.

DIFFUSIVE PARTICLE ACCELERATION IN SHOCKED, VISCOUS ACCRETION DISKS: GREEN'S FUNCTION ENERGY DISTRIBUTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Becker, Peter A.; Das, Santabrata; Le, Truong, E-mail: pbecker@gmu.edu, E-mail: sbdas@iitg.ernet.in, E-mail: truong.le@nhrec.org

2011-12-10

The acceleration of relativistic particles in a viscous accretion disk containing a standing shock is investigated as a possible explanation for the energetic outflows observed around radio-loud black holes. The energy/space distribution of the accelerated particles is computed by solving a transport equation that includes the effects of first-order Fermi acceleration, bulk advection, spatial diffusion, and particle escape. The velocity profile of the accreting gas is described using a model for shocked viscous disks recently developed by the authors, and the corresponding Green's function distribution for the accelerated particles in the disk and the outflow is obtained using a classicalmore » method based on eigenfunction analysis. The accretion-driven, diffusive shock acceleration scenario explored here is conceptually similar to the standard model for the acceleration of cosmic rays at supernova-driven shocks. However, in the disk application, the distribution of the accelerated particles is much harder than would be expected for a plane-parallel shock with the same compression ratio. Hence the disk environment plays a key role in enhancing the efficiency of the shock acceleration process. The presence of the shock helps to stabilize the disk by reducing the Bernoulli parameter, while channeling the excess binding energy into the escaping relativistic particles. In applications to M87 and Sgr A*, we find that the kinetic power in the jet is {approx}0.01 M-dot c{sup 2}, and the outflowing relativistic particles have a mean energy {approx}300 times larger than that of the thermal gas in the disk at the shock radius. Our results suggest that a standing shock may be an essential ingredient in accretion onto underfed black holes, helping to resolve the long-standing problem of the stability of advection-dominated accretion disks.« less

Role of protein and amino acids in promoting lean mass accretion with resistance exercise and attenuating lean mass loss during energy deficit in humans.

PubMed

Churchward-Venne, Tyler A; Murphy, Caoileann H; Longland, Thomas M; Phillips, Stuart M

2013-08-01

Amino acids are major nutrient regulators of muscle protein turnover. After protein ingestion, hyperaminoacidemia stimulates increased rates of skeletal muscle protein synthesis, suppresses muscle protein breakdown, and promotes net muscle protein accretion for several hours. These acute observations form the basis for strategized protein intake to promote lean mass accretion, or prevent lean mass loss over the long term. However, factors such as protein dose, protein source, and timing of intake are important in mediating the anabolic effects of amino acids on skeletal muscle and must be considered within the context of evaluating the reported efficacy of long-term studies investigating protein supplementation as part of a dietary strategy to promote lean mass accretion and/or prevent lean mass loss. Current research suggests that dietary protein supplementation can augment resistance exercise-mediated gains in skeletal muscle mass and strength and can preserve skeletal muscle mass during periods of diet-induced energy restriction. Perhaps less appreciated, protein supplementation can augment resistance training-mediated gains in skeletal muscle mass even in individuals habitually consuming 'adequate' (i.e., >0.8 g kg⁻¹ day⁻¹) protein. Additionally, overfeeding energy with moderate to high-protein intake (15-25 % protein or 1.8-3.0 g kg⁻¹ day⁻¹) is associated with lean, but not fat mass accretion, when compared to overfeeding energy with low protein intake (5 % protein or ~0.68 g kg⁻¹ day⁻¹). Amino acids represent primary nutrient regulators of skeletal muscle anabolism, capable of enhancing lean mass accretion with resistance exercise and attenuating the loss of lean mass during periods of energy deficit, although factors such as protein dose, protein source, and timing of intake are likely important in mediating these effects.

Harnessing the power of macrophages/monocytes for enhanced bone tissue engineering.

PubMed

Dong, Lei; Wang, Chunming

2013-06-01

Bone tissue engineering has attracted considerable attention as a promising treatment modality for severe bone degeneration. The pressing need for more sophisticated and fully functional bone substitutes has spurred a refocus on the development of bone constructs in a way more comparable to the physiological process. Current research is increasingly revealing the central roles of macrophages/monocytes in regulating bone development and repair, so we propose that these immunocytes can play a similar pivotal role in directing engineered bone regeneration. Accordingly, we discuss two possible strategies to exemplify how the distinctive power of macrophages/monocytes--particularly their cytokine-secretion ability and chemotactic response to foreign materials--can be harnessed to enhance the performance of bone tissue engineering applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

An Indication of the Enhanced Circumstellar Matter Near the Orbital Plane of the Symbiotic Star EG And

NASA Astrophysics Data System (ADS)

Shagatova, N.; Skopal, A.

2015-07-01

In this contribution we derive the velocity profile of the material produced by the giant in the symbiotic binary EG And, and the corresponding mass loss rate. Our analysis revealed a significant enhancement of the wind material along the binary plane, which allows a high efficiency of the wind transfer onto the accreting white dwarf.

Contrast-enhanced Magnetic Resonance Imaging of Pelvic Bone Metastases at 3.0 T: Comparison Between 3-dimensional T1-weighted CAIPIRINHA-VIBE Sequence and 2-dimensional T1-weighted Turbo Spin-Echo Sequence.

PubMed

Yoon, Min A; Hong, Suk-Joo; Lee, Kyu-Chong; Lee, Chang Hee

2018-06-12

This study aimed to compare 3-dimensional T1-weighted gradient-echo sequence (CAIPIRINHA-volumetric interpolated breath-hold examination [VIBE]) with 2-dimensional T1-weighted turbo spin-echo sequence for contrast-enhanced magnetic resonance imaging (MRI) of pelvic bone metastases at 3.0 T. Thirty-one contrast-enhanced MRIs of pelvic bone metastases were included. Two contrast-enhanced sequences were evaluated for the following parameters: overall image quality, sharpness of pelvic bone, iliac vessel clarity, artifact severity, and conspicuity and edge sharpness of the smallest metastases. Quantitative analysis was performed by calculating signal-to-noise ratio and contrast-to-noise ratio of the smallest metastases. Significant differences between the 2 sequences were assessed. CAIPIRINHA-VIBE had higher scores for overall image quality, pelvic bone sharpness, iliac vessel clarity, and edge sharpness of the metastatic lesions, and had less artifacts (all P < 0.05). There was no significant difference in conspicuity, signal-to-noise ratio, or contrast-to-noise ratio of the smallest metastases (P > 0.05). Our results suggest that CAIPIRINHA-VIBE may be superior to turbo spin-echo for contrast-enhanced MRI of pelvic bone metastases at 3.0 T.

Effect of Adipose Tissue-Derived Osteogenic and Endothelial Cells on Bone Allograft Osteogenesis and Vascularization in Critical-Sized Calvarial Defects

DTIC Science & Technology

2012-05-10

1% peni - cillin/streptomycin, and 50 ng/mL recombinant rat VEGF-C (Promocell, Heidelberg, Germany). The media were changed every other day for 8...various animal models that have demonstrated an enhanced osteogenic effect after treating bone allografts with adipose tissue or bone marrow-derived... enhanced 1560 CORNEJO ET AL. performance of bone allografts using osteogenic differentiated adipose derived mesenchymal stem cells. Biomaterials 32, 8880

A novel role for cathepsin K in periosteal osteoclast precursors during fracture repair.

PubMed

Walia, Bhavita; Lingenheld, Elizabeth; Duong, Le; Sanjay, Archana; Drissi, Hicham

2018-03-01

Osteoporosis management is currently centered around bisphosphonates, which inhibit osteoclast (OC) bone resorption but do not affect bone formation. This reduces fracture risk, but fails to restore healthy bone remodeling. Studies in animal models showed that cathepsin K (CatK) inhibition by genetic deletion or chemical inhibitors maintained bone formation while abrogating resorption during bone remodeling and stimulated periosteal bone modeling. Recently, periosteal mononuclear tartrate-resistant acid phosphatase-positive (TRAP + ) osteoclast precursors (OCPs) were shown to augment angiogenesis-coupled osteogenesis. CatK gene deletion increased osteoblast differentiation via enhanced OCP and OC secretion of platelet-derived growth factor (PDGF)-BB and sphingosine 1 phosphate. The effects of periosteum-derived OCPs on bone remodeling are unknown, particularly with regard to fracture repair. We hypothesized that periosteal OCPs derived from CatK-null (Ctsk -/- ) mice may enhance periosteal bone formation during fracture repair. We found fewer periosteal OCPs in Ctsk -/- mice under homeostatic conditions; however, after fracture, this population increased in number relative to that seen in wild-type (WT) mice. Enhanced TRAP staining and greater expression of PDGF-BB were observed in fractured Ctsk -/- femurs relative to WT femurs. This early pattern of augmented PDGF-BB expression in Ctsk -/- mice may contribute to improved fracture healing by enhancing callus mineralization in Ctsk -/- mice. © 2018 New York Academy of Sciences.

Implementation of Combined Feather and Surface-Normal Ice Growth Models in LEWICE/X

NASA Technical Reports Server (NTRS)

Velazquez, M. T.; Hansman, R. J., Jr.

1995-01-01

Experimental observations have shown that discrete rime ice growths called feathers, which grow in approximately the direction of water droplet impingement, play an important role in the growth of ice on accreting surfaces for some thermodynamic conditions. An improved physical model of ice accretion has been implemented in the LEWICE 2D panel-based ice accretion code maintained by the NASA Lewis Research Center. The LEWICE/X model of ice accretion explicitly simulates regions of feather growth within the framework of the LEWICE model. Water droplets impinging on an accreting surface are withheld from the normal LEWICE mass/energy balance and handled in a separate routine; ice growth resulting from these droplets is performed with enhanced convective heat transfer approximately along droplet impingement directions. An independent underlying ice shape is grown along surface normals using the unmodified LEWICE method. The resulting dual-surface ice shape models roughness-induced feather growth observed in icing wind tunnel tests. Experiments indicate that the exact direction of feather growth is dependent on external conditions. Data is presented to support a linear variation of growth direction with temperature and cloud water content. Test runs of LEWICE/X indicate that the sizes of surface regions containing feathers are influenced by initial roughness element height. This suggests that a previous argument that feather region size is determined by boundary layer transition may be incorrect. Simulation results for two typical test cases give improved shape agreement over unmodified LEWICE.

Adrenarche and bone modeling and remodeling at the proximal radius: weak androgens make stronger cortical bone in healthy children.

PubMed

Remer, Thomas; Boye, Kai R; Hartmann, Michaela; Neu, Christina M; Schoenau, Eckhard; Manz, Friedrich; Wudy, Stefan A

2003-08-01

Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children. Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth. Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6-18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry. We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001)--reflecting, at least in part, reduction in intracortical remodeling-were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables (except PC) when, instead of C19 and C21, specific dehydroepiandrosterone metabolites were included as independent variables in the multiple regression model. During development of pubic hair (pubarche), muscularity and pubertal stage rather than adrenarchal hormones seemed to influence bone variables. Our study shows that especially the prepubarchal increase in adrenal androgen secretion plays an independent role in the accretion of proximal radial diaphyseal bone strength in healthy children.

Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis

NASA Astrophysics Data System (ADS)

Mencía Castaño, Irene; Curtin, Caroline M.; Duffy, Garry P.; O'Brien, Fergal J.

2016-06-01

Bone grafts are the second most transplanted materials worldwide at a global cost to healthcare systems valued over $30 billion every year. The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge. This study describes how the functionalisation of porous collagen-nanohydroxyapatite (nHA) scaffolds with miR-133a inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2. This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications. The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics.

Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal-Stem Cells Identified Candidates for Bone Regeneration.

PubMed

Chang, Chi-Chih; Venø, Morten T; Chen, Li; Ditzel, Nicholas; Le, Dang Q S; Dillschneider, Philipp; Kassem, Moustapha; Kjems, Jørgen

2018-02-07

Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin-dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs delivered locally from an implanted scaffold can provide a promising approach for enhanced bone regeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Enhanced accumulation of adipocytes in bone marrow stromal cells in the presence of increased extracellular and intracellular [Ca{sup 2+}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hashimoto, Ryota, E-mail: hryota@juntendo.ac.jp; Katoh, Youichi, E-mail: katoyo@juntendo-urayasu.jp; Nakamura, Kyoko

2012-07-13

Highlights: Black-Right-Pointing-Pointer High [Ca{sup 2+}]{sub o} enhances adipocyte accumulation in the presence of adipogenic inducers. Black-Right-Pointing-Pointer High [Ca{sup 2+}]{sub o} enhances both proliferation and adipocyte differentiation in BMSCs. Black-Right-Pointing-Pointer High [Ca{sup 2+}]{sub o} induces an increase in [Ca{sup 2+}]{sub o} in BMSCs. Black-Right-Pointing-Pointer An intracellular Ca{sup 2+} chelator suppresses the enhancement in adipocyte accumulation. Black-Right-Pointing-Pointer Controlling [Ca{sup 2+}]{sub o} may govern the balance of adipocyte and osteoblast development. -- Abstract: The bone marrow stroma contains osteoblasts and adipocytes that have a common precursor: the pluripotent mesenchymal stem cell found in bone marrow stromal cells (BMSCs). Local bone marrow Ca{sup 2+}more » levels can reach high concentrations due to bone resorption, which is one of the notable features of the bone marrow stroma. Here, we describe the effects of high [Ca{sup 2+}]{sub o} on the accumulation of adipocytes in the bone marrow stroma. Using primary mouse BMSCs, we evaluated the level of adipocyte accumulation by measuring Oil Red O staining and glycerol-3-phosphate dehydrogenase (GPDH) activity. High [Ca{sup 2+}]{sub o} enhanced the accumulation of adipocytes following treatment with both insulin and dexamethasone together but not in the absence of this treatment. This enhanced accumulation was the result of both the accelerated proliferation of BMSCs and their differentiation into adipocytes. Using the fura-2 method, we also showed that high [Ca{sup 2+}]{sub o} induces an increase in [Ca{sup 2+}]{sub i}. An intracellular Ca{sup 2+} chelator suppressed the enhancement in adipocyte accumulation due to increased [Ca{sup 2+}]{sub o} in BMSCs. These data suggest a new role for extracellular Ca{sup 2+} in the bone marrow stroma: increased [Ca{sup 2+}]{sub o} induces an increase in [Ca{sup 2+}]{sub i} levels, which in turn enhances the accumulation of adipocytes under certain conditions.« less

Engineering bone grafts with enhanced bone marrow and native scaffolds.

PubMed

Hung, Ben P; Salter, Erin K; Temple, Josh; Mundinger, Gerhard S; Brown, Emile N; Brazio, Philip; Rodriguez, Eduardo D; Grayson, Warren L

2013-01-01

The translation of tissue engineering approaches to the clinic has been hampered by the inability to find suitable multipotent cell sources requiring minimal in vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long bone medullary canals and isolating the solid marrow putty, has large quantities of stem cells and demonstrates significant potential to regenerate bone tissues. eBM, however, cannot impart immediate load-bearing mechanical integrity or maintain the gross anatomical structure to guide bone healing. Yet, its putty-like consistency creates a challenge for obtaining the uniform seeding necessary to effectively combine it with porous scaffolds. In this study, we examined the potential for combining eBM with mechanically strong, osteoinductive trabecular bone scaffolds for bone regeneration by creating channels into scaffolds for seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using a Synthes reamer-irrigator-aspirator device, analyzed histologically, and digested to extract cells and characterize their differentiation potential. To evaluate bone tissue formation, eBM was seeded into the channels in collagen-coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks, harvested and assessed for tissue distribution and bone formation. Our data demonstrates that eBM is a heterogenous tissue containing multipotent cell populations. Furthermore, coating scaffolds with a collagen hydrogel significantly enhanced cellular migration, promoted uniform tissue development and increased bone mineral deposition. These findings suggest the potential for generating customized autologous bone grafts for treating critical-sized bone defects by combining a readily available eBM cell source with decellularized trabecular bone scaffolds. © 2013 S. Karger AG, Basel

Magnetic Resonance Imaging of Tumor Associated Macrophages: Clinical Translation.

PubMed

Aghighi, Maryam; Theruvath, Ashok Joseph; Pareek, Anuj; Pisani, Laura; Alford, Raphael; Muehe, Anne Monika; Sethi, Tarsheen K; Holdsworth, Samantha J; Hazard, Florette K; Gratzinger, Dita; Luna-Fineman, Sandra; Advani, Ranjana H; Spunt, Sheri L; Daldrup-Link, Heike E

2018-05-15

Tumor associated macrophages (TAM) in malignant tumors have been linked to tumor aggressiveness and represent a new target for cancer immunotherapy. As new TAM-targeted immunotherapies are entering clinical trials, it is important to detect and quantify TAM with non-invasive imaging techniques. The purpose of this study was to determine if ferumoxytol-enhanced MRI can detect TAM in lymphomas and bone sarcomas of pediatric patients and young adults. In a first-in-patient , IRB-approved prospective clinical trial, 25 pediatric and young adult patients with lymphoma or bone sarcoma underwent ferumoxytol-enhanced MRI. To confirm ferumoxytol enhancement, five pilot patients (2 lymphoma, 3 bone sarcoma) underwent pre- and post-contrast MRI. Subsequently, 20 patients (10 lymphoma, 10 bone sarcoma) underwent ferumoxytol-enhanced MRI 24-48 hours after intravenous injection, followed by tumor biopsy/resection and macrophage staining. To determine if ferumoxytol-MRI can differentiate tumors with different TAM content, we compared T2* relaxation times of lymphomas and bone sarcomas. Tumor T2* values of 20 patients were correlated with CD68+ and CD163+ TAM quantities on histopathology. Significant ferumoxytol tumor enhancement was noted on post-contrast scans compared to pre-contrast scans ( P = 0.036). Bone sarcomas and lymphomas demonstrated significantly different MRI enhancement and TAM density ( P < 0.05). Within each tumor group, T2* signal enhancement on MR images correlated significantly with the density of CD68+ and CD163+ TAM ( P < 0.05). Ferumoxytol-enhanced MRI is immediately clinically applicable and could be used to stratify patients with TAM-rich tumors to immune-targeted therapies and to monitor tumor response to these therapies. Copyright ©2018, American Association for Cancer Research.

The Effect of Interferon-γ and Zoledronate Treatment on Alpha-Tricalcium Phosphate/Collagen Sponge-Mediated Bone-Tissue Engineering

PubMed Central

Li, Peiqi; Hashimoto, Yoshiya; Honda, Yoshitomo; Arima, Yoshiyuki; Matsumoto, Naoyuki

2015-01-01

Inflammatory responses are frequently associated with the expression of inflammatory cytokines and severe osteoclastogenesis, which significantly affect the efficacy of biomaterials. Recent findings have suggested that interferon (IFN)-γ and zoledronate (Zol) are effective inhibitors of osteoclastogenesis. However, little is known regarding the utility of IFN-γ and Zol in bone tissue engineering. In this study, we generated rat models by generating critically sized defects in calvarias implanted with an alpha-tricalcium phosphate/collagen sponge (α-TCP/CS). At four weeks post-implantation, the rats were divided into IFN-γ, Zol, and control (no treatment) groups. Compared with the control group, the IFN-γ and Zol groups showed remarkable attenuation of severe osteoclastogenesis, leading to a significant enhancement in bone mass. Histomorphometric data and mRNA expression patterns in IFN-γ and Zol-injected rats reflected high bone-turnover with increased bone formation, a reduction in osteoclast numbers, and tumor necrosis factor-α expression. Our results demonstrated that the administration of IFN-γ and Zol enhanced bone regeneration of α-TCP/CS implants by enhancing bone formation, while hampering excess bone resorption. PMID:26516841

Hydrodynamic models for novae with ejecta rich in oxygen, neon and magnesium

NASA Technical Reports Server (NTRS)

Starrfield, S.; Sparks, W. M.; Truran, J. W.

1985-01-01

The characteristics of a new class of novae are identified and explained. This class consists of those objects that have been observed to eject material rich in oxygen, neon, magnesium, and aluminum at high velocities. We propose that for this class of novae the outburst is occurring not on a carbon-oxygen white dwarf but on an oxygen-neon-magnesium white dwarf which has evolved from a star which had a main sequence mass of approx. 8 solar masses to approx. 12 solar masses. An outburst was simulated by evolving 1.25 solar mass white dwarfs accreting hydrogen rich material at various rates. The effective enrichment of the envelope by ONeMg material from the core is simulated by enhancing oxygen in the accreted layers. The resulting evolutionary sequences can eject the entire accreted envelope plus core material at high velocities. They can also become super-Eddington at maximum bolometric luminosity. The expected frequency of such events (approx. 1/4) is in good agreement with the observed numbers of these novae.

Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice.

PubMed

Reyes, Ricardo; Rodríguez, Jose Antonio; Orbe, Josune; Arnau, María Rosa; Évora, Carmen; Delgado, Araceli

2018-11-01

The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control. Encapsulation efficiency was assessed and in vivo release kinetics of BMP-2 and MMP10 were examined over 14 days. Histological analyses were used to analyze bone formation after four and eight weeks. Combination with MMP10 (30 ng) significantly enhanced BMP-2 (600 ng)-mediated osteogenesis, as confirmed by the increase in percentage of bone fill (p < .05) at four weeks. Moreover, it also increased mineral apposition rate (p < .05), measured by double labeling with tetracycline and calceine. MMP10 accelerates bone repair by enhancing BMP-2-promoted bone healing and improving the mineralization rate. In conclusion combination of MMP10 and BMP-2 may become a promising strategy for repair and regeneration of bone defects.

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation

PubMed Central

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy

2012-01-01

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 µg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm3, respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls. PMID:21863314

Comparison of image enhancement methods for the effective diagnosis in successive whole-body bone scans.

PubMed

Jeong, Chang Bu; Kim, Kwang Gi; Kim, Tae Sung; Kim, Seok Ki

2011-06-01

Whole-body bone scan is one of the most frequent diagnostic procedures in nuclear medicine. Especially, it plays a significant role in important procedures such as the diagnosis of osseous metastasis and evaluation of osseous tumor response to chemotherapy and radiation therapy. It can also be used to monitor the possibility of any recurrence of the tumor. However, it is a very time-consuming effort for radiologists to quantify subtle interval changes between successive whole-body bone scans because of many variations such as intensity, geometry, and morphology. In this paper, we present the most effective method of image enhancement based on histograms, which may assist radiologists in interpreting successive whole-body bone scans effectively. Forty-eight successive whole-body bone scans from 10 patients were obtained and evaluated using six methods of image enhancement based on histograms: histogram equalization, brightness-preserving bi-histogram equalization, contrast-limited adaptive histogram equalization, end-in search, histogram matching, and exact histogram matching (EHM). Comparison of the results of the different methods was made using three similarity measures peak signal-to-noise ratio, histogram intersection, and structural similarity. Image enhancement of successive bone scans using EHM showed the best results out of the six methods measured for all similarity measures. EHM is the best method of image enhancement based on histograms for diagnosing successive whole-body bone scans. The method for successive whole-body bone scans has the potential to greatly assist radiologists quantify interval changes more accurately and quickly by compensating for the variable nature of intensity information. Consequently, it can improve radiologists' diagnostic accuracy as well as reduce reading time for detecting interval changes.

Can the adult skeleton recover lost bone?

NASA Technical Reports Server (NTRS)

Leblanc, Adrian; Schneider, Victor

1991-01-01

The loss of bone mineral with aging and subsequent development of osteoporosis is a common problem in elderly women, and as life expectancy increases, in elderly men as well. Space flight also causes bone loss and could be a limiting factor for long duration missions, such as, a Mars expedition or extended occupation of a Space Station. Before effective countermeasures can be devised, a thorough knowledge of the extent, location, and rate of bone loss during weightlessness is needed from actual space flight data or ground-based disuse models. In addition, the rate and extent that these losses are reversed after return from space flight are of primary importance. Although the mechanisms are not likely to be the same in aging and space flight, there are common elements. For example, strategies developed to prevent disuse bone loss or to enhance the rate of recovery following space flight might have direct applicability to clinical medicine. For various reasons, little attention has been given to recovery of bone mass following space flight. As a prelude to the design of strategies to enhance recovery of bone, this paper reviews published literature related to bone recovery in the adult. We conclude that recovery can be expected, but the rate and extent will be individual and bone site dependent. The development of strategies to encourage or enhance bone formation following space flight may be as important as implementing countermeasures during flight.

Enhanced Hα activity at periastron in the young and massive spectroscopic binary HD 200775

NASA Astrophysics Data System (ADS)

Benisty, M.; Perraut, K.; Mourard, D.; Stee, P.; Lima, G. H. R. A.; Le Bouquin, J. B.; Borges Fernandes, M.; Chesneau, O.; Nardetto, N.; Tallon-Bosc, I.; McAlister, H.; Ten Brummelaar, T.; Ridgway, S.; Sturmann, J.; Sturmann, L.; Turner, N.; Farrington, C.; Goldfinger, P. J.

2013-07-01

Context. Young close binaries clear central cavities in their surrounding circumbinary disk from which the stellar objects can still accrete material. This process takes place within the first astronomical unit and is still not well constrained because the observational evidence has been gathered, until now, only by means of spectroscopy. Theoretical models for T Tauri stars in close binaries predict a variability of the hydrogen emission lines attributable to periodic changes in the accretion rates as the secondary approaches periastron. Whether a similar scenario applies to more massive objects is unclear, and still needs to be proven observationally. Aims: The young object HD 200775 (MWC 361) is a massive spectroscopic binary (separation of ~15.9 mas, ~5.0 AU), with uncertain classification (early/late Be), that shows a strong and variable Hα emission. We aim to study the mechanisms that produce the Hα line at the AU-scale, and their dependence on binarity. Methods: Combining the radial velocity measurements and astrometric data available in the literature, we determined new orbital parameters and revised the distance to 320 ± 51 pc. With the VEGA instrument on the CHARA array, we spatially and spectrally resolved the Hα emission of HD 200775 on a scale of a few milliarcseconds, at low and medium spectral resolutions (R ~ 1600 and 5000). Our observations cover a single orbital period (~3.6 years). Spectra, spectral visibilities, and differential phases have been derived. A simple analytical model of a face-on Gaussian located along the binary axis was used to analyze the interferometric observables over the spectral range. Results: We observe that the Hα equivalent width varies with the orbital phase, and increases close to periastron, as expected from theoretical models that predict an increase of the mass transfer from the circumbinary disk to the primary disk. In addition, using spectral visibilities and differential phases, we find marginal variations of the typical extent of the Hα emission (at 1 to 2σ level) and location (at 1 to 5σ level). The spatial extent of the Hα emission, as probed by the Gaussian FWHM, is minimum at the ascending node (0.67 ± 0.20 mas, i.e., 0.22 ± 0.06 AU), and more than doubles at the periastron. In addition, the Gaussian photocenter is slightly displaced in the direction opposite to the secondary, ruling out the scenario in which all or most of the Hα emission is due to accretion onto the secondary. This favors a scenario in which the primary is responsible for the enhanced Hα activity at periastron. These findings, together with the wide Hα line profile, may be due to a non-spherical wind enhanced at periastron. Conclusions: For the first time in a system of this kind, we spatially resolve the Hα line and estimate that it is emitted in a region larger than the one usually inferred in accretion processes. The Hα line could be emitted in a stellar or disk-wind, enhanced at periastron as a result of gravitational perturbation, after a period of increased mass accretion rate. Our results suggest a strong connection between accretion and ejection in these massive objects, consistent with the predictions for lower-mass close binaries. Based on observations made with the VEGA/CHARA instrument.

Conditions for Optimal Growth of Black Hole Seeds

NASA Astrophysics Data System (ADS)

Pacucci, Fabio; Natarajan, Priyamvada; Volonteri, Marta; Cappelluti, Nico; Urry, C. Megan

2017-12-01

Supermassive black holes weighing up to ˜109 M ⊙ are in place by z ˜ 7, when the age of the universe is ≲1 Gyr. This implies a time crunch for their growth, since such high masses cannot be easily reached in standard accretion scenarios. Here, we explore the physical conditions that would lead to optimal growth wherein stable super-Eddington accretion would be permitted. Our analysis suggests that the preponderance of optimal conditions depends on two key parameters: the black hole mass and the host galaxy central gas density. In the high-efficiency region of this parameter space, a continuous stream of gas can accrete onto the black hole from large to small spatial scales, assuming a global isothermal profile for the host galaxy. Using analytical initial mass functions for black hole seeds, we find an enhanced probability of high-efficiency growth for seeds with initial masses ≳104 M ⊙. Our picture suggests that a large population of high-z lower-mass black holes that formed in the low-efficiency region, with low duty cycles and accretion rates, might remain undetectable as quasars, since we predict their bolometric luminosities to be ≲1041 erg s-1. The presence of these sources might be revealed only via gravitational wave detections of their mergers.

General Relativistic Effects and QPOs in X-Ray Binaries

NASA Astrophysics Data System (ADS)

Markovic, D.; Lamb, F. K.

We have investigated whether general relativistic effects may be responsible for some of the quasi-periodic X-ray brightness oscillations (QPOs) observed in low-mass binary systems containing accreting neutron stars and black hole candidates. In particular, we have computed the motions of accreting gas in the strong gravitational fields near such objects and have explored possible mechanisms for producing X-ray flux oscillations. We have discovered a family of weakly damped global gravitomagnetic (Lense-Thirring) warping modes of the inner (viscous) accretion disk that have precession frequencies ranging up to the single-particle gravitomagnetic precession frequency at the inner edge of the disk, which is about 30 Hz if the disk extends inward to the innermost stable circular orbit around a compact object of solar mass with dimensionless angular momentum cJ/GM2 ~ 0.2. Precession of regions of enhanced viscous dissipation or modulation of the accretion flow by the precession may produce observable periodic variation of the X-ray flux. Detectable effects might also be produced if the gas in the inner disk breaks up into a collection of distinct clumps. We have analyzed the dynamics of such clumps as well as the conditions required for their formation and survival on time scales long enough to produce QPOs with the coherence observed in low-mass X-ray binaries.

Numerical Prediction of the Onset of the Magnetorotational Instability in the Princeton MRI Apparatus

NASA Astrophysics Data System (ADS)

Gilson, Erik; Caspary, Kyle; Ebrahimi, Fatima; Goodman, Jeremy; Ji, Hantao; Nuñez, Tahiri; Wei, Xing

2016-10-01

The liquid metal magnetorotational instability experiment at PPPL is designed to search for the MRI in a controlled laboratory setup. MRI is thought to be the primary mechanism behind turbulence in accretion disks, leading to an enhanced effective viscosity that can explain observed fast accretion rates. The apparatus has several key differences from an accretion disk. The top and bottom surfaces of the vessel exert stresses on the surfaces of the working fluid. There are no surface stresses on an accretion disk, but rather a free-surface. To interpret experimental results, the Spectral Finite Element Maxwell and Navier Stokes (SFEMaNS) code (Guermond et al., 2009) has been used to simulate experiments in the MRI apparatus and study MRI onset in the presence of residual flows induced by the boundaries. These Ekman flows lead to the generation of radial magnetic fields that can obfuscate the MRI signal. Simulation results are presented that show the full spatial distribution of the velocity field and the magnetic field over a range of experimental operating parameters, including both above and below the expected MRI threshold. Both the residual flow and the radial magnetic field at the location of the diagnostics are computed for comparisons with experimental results. This research is supported by DOE, NSF, and NASA.

NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation

PubMed Central

Yao, Zhenqiang; Li, Yanyun; Yin, Xiaoxiang; Dong, Yufeng; Xing, Lianping; Boyce, Brendan F.

2013-01-01

RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through non-canonical signaling, but they involved a complex knockout mouse model and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runx2. In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

X-ray reflection from cold white dwarfs in magnetic cataclysmic variables

NASA Astrophysics Data System (ADS)

Hayashi, Takayuki; Kitaguchi, Takao; Ishida, Manabu

2018-02-01

We model X-ray reflection from white dwarfs (WDs) in magnetic cataclysmic variables (mCVs) using a Monte Carlo simulation. A point source with a power-law spectrum or a realistic post-shock accretion column (PSAC) source irradiates a cool and spherical WD. The PSAC source emits thermal spectra of various temperatures stratified along the column according to the PSAC model. In the point-source simulation, we confirm the following: a source harder and nearer to the WD enhances the reflection; higher iron abundance enhances the equivalent widths (EWs) of fluorescent iron Kα1, 2 lines and their Compton shoulder, and increases the cut-off energy of a Compton hump; significant reflection appears from an area that is more than 90° apart from the position right under the point X-ray source because of the WD curvature. The PSAC simulation reveals the following: a more massive WD basically enhances the intensities of the fluorescent iron Kα1, 2 lines and the Compton hump, except for some specific accretion rate, because the more massive WD makes a hotter PSAC from which higher-energy X-rays are preferentially emitted; a larger specific accretion rate monotonically enhances the reflection because it makes a hotter and shorter PSAC; the intrinsic thermal component hardens by occultation of the cool base of the PSAC by the WD. We quantitatively estimate the influences of the parameters on the EWs and the Compton hump with both types of source. We also calculate X-ray modulation profiles brought about by the WD spin. These depend on the angles of the spin axis from the line of sight and from the PSAC, and on whether the two PSACs can be seen. The reflection spectral model and the modulation model involve the fluorescent lines and the Compton hump and can directly be compared to the data, which allows us to estimate these geometrical parameters with unprecedented accuracy.

Design and development of novel hyaluronate-modified nanoparticles for combo-delivery of curcumin and alendronate: Fabrication, characterization, and cellular and molecular evidence of enhanced bone regeneration.

PubMed

Dong, Jinlei; Thu, Hnin Ei; Abourehab, Mohammed A S; Hussain, Zahid

2018-05-18

Osteoporosis is a medical condition of fragile bones with an increased susceptibility to bone fracture. Despite having availability of a wide range of pharmacological agents, prevalence of this metabolic disorder is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR), in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles were decorated with hyaluronic acid which is a well-documented biomacromolecule having exceptional bone regenerating potential. The optimized nanoformulation was evaluated for bone regeneration efficacy by assessing the time-mannered modulation in the proliferation, differentiation, and mineralization of MC3T3-E1 cells, a pre-osteoblast model. Moreover, the time-mannered expressions of various bone-forming protein biomarkers including bone morphogenetic protein, runt related transcription factor 2, and osteocalcin were assessed in the cell lysates. Results revealed that HA-ALN/CUR NPs provoke remarkable increase in proliferation, differentiation, and mineralization in the ECM of MC3T3-E1 cells which ultimately leads to enhanced bone formation. This new strategy employing simultaneous delivery of anti-resorptive and bone forming agents would open new horizons for the scientists as an efficient alternative pharmacotherapy for the management of osteoporosis. Copyright © 2017. Published by Elsevier B.V.

Bone regeneration in critical bone defects using three-dimensionally printed β-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2.

PubMed

Ishack, Stephanie; Mediero, Aranzazu; Wilder, Tuere; Ricci, John L; Cronstein, Bruce N

2017-02-01

Bone defects resulting from trauma or infection need timely and effective treatments to restore damaged bone. Using specialized three-dimensional (3D) printing technology we have created custom 3D scaffolds of hydroxyapatite (HA)/beta-tri-calcium phosphate (β-TCP) to promote bone repair. To further enhance bone regeneration we have coated the scaffolds with dipyridamole, an agent that increases local adenosine levels by blocking cellular uptake of adenosine. Nearly 15% HA:85% β-TCP scaffolds were designed using Robocad software, fabricated using a 3D Robocasting system, and sintered at 1100°C for 4 h. Scaffolds were coated with BMP-2 (200 ng mL -1 ), dypiridamole 100 µM or saline and implanted in C57B6 and adenosine A2A receptor knockout (A2AKO) mice with 3 mm cranial critical bone defects for 2-8 weeks. Dipyridamole release from scaffold was assayed spectrophotometrically. MicroCT and histological analysis were performed. Micro-computed tomography (microCT) showed significant bone formation and remodeling in HA/β-TCP-dipyridamole and HA/β-TCP-BMP-2 scaffolds when compared to scaffolds immersed in vehicle at 2, 4, and 8 weeks (n = 5 per group; p ≤ 0.05, p ≤ 0.05, and p ≤ 0.01, respectively). Histological analysis showed increased bone formation and a trend toward increased remodeling in HA/β-TCP- dipyridamole and HA/β-TCP-BMP-2 scaffolds. Coating scaffolds with dipyridamole did not enhance bone regeneration in A2AKO mice. In conclusion, scaffolds printed with HA/β-TCP promote bone regeneration in critical bone defects and coating these scaffolds with agents that stimulate A2A receptors and growth factors can further enhance bone regeneration. These coated scaffolds may be very useful for treating critical bone defects due to trauma, infection or other causes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 366-375, 2017. © 2015 Wiley Periodicals, Inc.

International longitudinal pediatric reference standards for bone mineral content.

PubMed

Baxter-Jones, Adam D G; Burrows, Melonie; Bachrach, Laura K; Lloyd, Tom; Petit, Moira; Macdonald, Heather; Mirwald, Robert L; Bailey, Don; McKay, Heather

2010-01-01

To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site-specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Women's Health Study (n=112) and Stanford's Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement between predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P<0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. We report similar findings for the PF and FN. Models for females for all sites were similar with age, height and weight as independent significant predictors of BMC accrual (P<0.05). We provide a tool to calculate a child's BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in pediatrics we recommend standards that are sex, age, size and ethnic specific. Copyright (c) 2009 Elsevier Inc. All rights reserved.

International Longitudinal Paediatric Reference Standards for Bone Mineral Content

PubMed Central

Baxter-Jones, Adam DG; McKay, Heather; Burrows, Melonie; Bachrach, Laura K; Lloyd, Tom; Petit, Moira; Macdonald, Heather; Mirwald, Robert L; Bailey, Don

2014-01-01

To render a diagnosis pediatricians rely upon reference standards for bone mineral density or bone mineral content, which are based on cross-sectional data from a relatively small sample of children. These standards are unable to adequately represent growth in a diverse pediatric population. Thus, the goal of this study was to develop sex and site specific standards for BMC using longitudinal data collected from four international sites in Canada and the United States. Data from four studies were combined; Saskatchewan Paediatric Bone Mineral Accrual Study (n=251), UBC Healthy Bones Study (n=382); Penn State Young Women’s Health Study (n=112) and Stanford’s Bone Mineral Accretion study (n=423). Males and females (8 to 25 years) were measured for whole body (WB), total proximal femur (PF), femoral neck (FN) and lumbar spine (LS) BMC (g). Data were analyzed using random effects models. Bland-Altman was used to investigate agreement in predicted and actual data. Age, height, weight and ethnicity independently predicted BMC accrual across sites (P <0.05). Compared to White males, Asian males had 31.8 (6.8) g less WB BMC accrual; Hispanic 75.4 (28.2) g less BMC accrual; Blacks 82.8 (26.3) g more BMC accrual with confounders of age, height and weight controlled. Similar findings were found for PF and FN. Female models for all sites were similar with age, height and weight all independent significant predictors of BMC accrual (P <0.05). We provide a tool to calculate a child’s BMC Z-score, accounting for age, size, sex and ethnicity. In conclusion, when interpreting BMC in paediatrics we recommend standards that are sex, age, size and ethnic specific. PMID:19854308

Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robling, Alexander G.; Kang, Kyung Shin; Bullock, Whitney A.

Here, sclerostin ( Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway. Sost is mechanically regulated at both mRNA and protein level such that loading represses and unloading enhances Sost expression, in osteocytes and in circulation. The non-coding evolutionarily conserved enhancer ECR5 has been previously reported as a transcriptional regulatory element required for modulating Sost expression in osteocytes. Here we explored the mechanisms by which ECR5, or several other putative transcriptional enhancers regulate Sost expression, in response to mechanical stimulation. We found that in vivo ulna loading is equally osteoanabolic in wildtype and Sostmore » –/– mice, although Sost is required for proper distribution of load-induced bone formation to regions of high strain. Using Luciferase reporters carrying the ECR5 non-coding enhancer and heterologous or homologous h SOST promoters, we found that ECR5 is mechanosensitive in vitro and that ECR5-driven Luciferase activity decreases in osteoblasts exposed to oscillatory fluid flow. Yet, ECR5–/– mice showed similar magnitude of load-induced bone formation and similar periosteal distribution of bone formation to high-strain regions compared to wildtype mice. Further, we found that in contrast to Sost–/– mice, which are resistant to disuse-induced bone loss, ECR5–/– mice lose bone upon unloading to a degree similar to wildtype control mice. ECR5 deletion did not abrogate positive effects of unloading on Sost, suggesting that additional transcriptional regulators and regulatory elements contribute to load-induced regulation of Sost.« less

Sost, independent of the non-coding enhancer ECR5, is required for bone mechanoadaptation

DOE PAGES

Robling, Alexander G.; Kang, Kyung Shin; Bullock, Whitney A.; ...

2016-09-04

Here, sclerostin ( Sost) is a negative regulator of bone formation that acts upon the Wnt signaling pathway. Sost is mechanically regulated at both mRNA and protein level such that loading represses and unloading enhances Sost expression, in osteocytes and in circulation. The non-coding evolutionarily conserved enhancer ECR5 has been previously reported as a transcriptional regulatory element required for modulating Sost expression in osteocytes. Here we explored the mechanisms by which ECR5, or several other putative transcriptional enhancers regulate Sost expression, in response to mechanical stimulation. We found that in vivo ulna loading is equally osteoanabolic in wildtype and Sostmore » –/– mice, although Sost is required for proper distribution of load-induced bone formation to regions of high strain. Using Luciferase reporters carrying the ECR5 non-coding enhancer and heterologous or homologous h SOST promoters, we found that ECR5 is mechanosensitive in vitro and that ECR5-driven Luciferase activity decreases in osteoblasts exposed to oscillatory fluid flow. Yet, ECR5–/– mice showed similar magnitude of load-induced bone formation and similar periosteal distribution of bone formation to high-strain regions compared to wildtype mice. Further, we found that in contrast to Sost–/– mice, which are resistant to disuse-induced bone loss, ECR5–/– mice lose bone upon unloading to a degree similar to wildtype control mice. ECR5 deletion did not abrogate positive effects of unloading on Sost, suggesting that additional transcriptional regulators and regulatory elements contribute to load-induced regulation of Sost.« less

Bone-to-bone Fixation Enhances Functional Healing of the Porcine Anterior Cruciate Ligament Using a Collagen-Platelet Composite

PubMed Central

Murray, Martha M.; Magarian, Elise; Zurakowski, David; Fleming, Braden C.

2010-01-01

Purpose The purpose of this study was to determine if providing bony stabilization between the tibia and femur would improve the structural properties of an “enhanced” ACL repair using a collagen-platelet composite when compared to the traditional (Marshall) suture technique. Methods Twelve pigs underwent unilateral ACL transection and were treated with sutures connecting the bony femoral ACL attachment site to the distal ACL stump (LIGAMENT group), or to the tibia via a bone tunnel (TIBIA group). A collagen-platelet composite was placed around the sutures to enhance the biologic repair in both groups. Anteroposterior (AP) knee laxity and the graft structural properties were measured after 15 weeks of healing in both the ACL-repaired and contralateral ACL-intact joints. Results Enhanced ACL repair with bone-to-bone fixation significantly improved yield load and linear stiffness of the ACL repairs (p<0.05) after 15 weeks of healing. However, laxity values of the knees were similar in both groups of repaired knees (p>0.10). Conclusions Using an enhanced ACL suture repair technique that includes bone-to-bone fixation to protect the repair in the initial healing stages resulted in an ACL with improved structural properties after 15 weeks in the porcine model. Clinical Relevance The healing response of an ACL suture repair using a collagen-platelet composite can be enhanced by providing bony stabilization between the tibia and femur to protect the graft during the initial healing process in a translational model. PMID:20810092

Microbial pathways and palaeoenvironmental conditions involved in the formation of phosphorite grains, Safaga District, Egypt

NASA Astrophysics Data System (ADS)

Salama, Walid; El-Kammar, Ahmed; Saunders, Martin; Morsy, Rania; Kong, Charlie

2015-07-01

Phosphatic grains of the shallow marine phosphorite deposits of Egypt are classified as either phosphatic bioclasts preserving biological structure (e.g. skeletal fragments such as fish bones and teeth) or phosphatic peloids and intraclasts. This study describes the destructive and constructive microbial pathways represented by bioerosion of bones by endolithic cyanobacteria and accretion of phosphatic peloids by bacteria. The palaeoenvironmental conditions and post-depositional/diagenetic history of these grains have also been considered. Scanning and transmission electron microscopy showed that the phosphatic peloids under transmitted light microscopy are composed mainly of microspheres (0.5 to 2.5 μm) similar in shape and size to coccoid-like bacteria. Chemical mapping showed that these microspheres are composed of carbonate-fluorapatite (CFA) and surrounded by degraded carbonaceous matrix. These grains are suggested to be reworked from pre-existing microbial mats during transgressive-regressive cycles affecting the southern Tethyan Campanian-Maastrichtian shallow continental shelf. The bioerosion of phosphatic bones is characterized by a network of meandering microborings that penetrated inward from the bone surface by endolithic cyanobacteria. The bioerosion of bones resulted in a gradual centripetal digestion and conversion of bones into micritic phosphate peloids. The bioerosion mechanism is probably started in the acidic sheath surrounding cyanobacteria followed by supersaturation of PO4 and reprecipitation of crystalline CFA as electron dense remineralized rims. Electron microprobe microanalyses showed that the remineralized microbored areas are higher in CaO, P2O5, and F and depleted in Cl, relative to unaltered bones. A gradual demineralization of remineralized rims followed by dissolution of cyanobacterial cells is probably occurred during diagenesis and meteoric water alteration leaving behind empty microborings. Bone exposed to meteoric water alteration is lower in CaO and P2O5 and higher in F and Cl than the unaltered bones. Understanding bone bioerosion has significant implications for palaeoenvironmental and taphonomic reconstruction, archaeological applications and a regional correlation of the late Cretaceous to Palaeogene phosphogenic province extending from Middle East to North Africa.

Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics.

PubMed

Lin, Kaili; Xia, Lunguo; Li, Haiyan; Jiang, Xinquan; Pan, Haobo; Xu, Yuanjin; Lu, William W; Zhang, Zhiyuan; Chang, Jiang

2013-12-01

The regeneration capacity of the osteoporotic bones is generally lower than that of the normal bones. Current methods of bone defect treatment for osteoporosis are not always satisfactory. Recent studies have shown that the silicate based biomaterials can stimulate osteogenesis and angiogenesis due to the silicon (Si) ions released from the materials, and enhance bone regeneration in vivo. Other studies showed that strontium (Sr) plays a distinct role on inhibiting bone resorption. Based on the hypothesis that the combination of Si and Sr may have synergetic effects on osteoporotic bone regeneration, the porous Sr-substituted calcium silicate (SrCS) ceramic scaffolds combining the functions of Sr and Si elements were developed with the goals to promote osteoporotic bone defect repair. The effects of the ionic extract from SrCS on osteogenic differentiation of bone marrow mesenchymal stem cells derived from ovariectomized rats (rBMSCs-OVX), angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) were investigated. The in vitro results showed that Sr and Si ions released from SrCS enhanced cell viability, alkaline phosphatase (ALP) activity, and mRNA expression levels of osteoblast-related genes of rBMSCs-OVX and expression of vascular endothelial growth factor (VEGF) without addition of extra osteogenic and angiogenic reagents. The activation in extracellular signal-related kinases (ERK) and p38 signaling pathways were observed in rBMSCs-OVX cultured in the extract of SrCS, and these effects could be blocked by ERK inhibitor PD98059, and P38 inhibitor SB203580, respectively. Furthermore, the ionic extract of SrCS stimulated HUVECs proliferation, differentiation and angiogenesis process. The in vivo experiments revealed that SrCS dramatically stimulated bone regeneration and angiogenesis in a critical sized OVX calvarial defect model, and the enhanced bone regeneration might be attributed to the modulation of osteogenic differentiation of endogenous mesenchymal stem cells (MSCs) and the inhibition of osteoclastogenesis, accompanying with the promotion of the angiogenic activity of endothelial cells (ECs). Copyright © 2013 Elsevier Ltd. All rights reserved.

Combination of BMP-2-releasing gelatin/β-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

PubMed

Yamamoto, Masaya; Hokugo, Akishige; Takahashi, Yoshitake; Nakano, Takayoshi; Hiraoka, Masahiro; Tabata, Yasuhiko

2015-07-01

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating β-tricalcium phosphate (β-TCP) granules (gelatin/β-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/β-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/β-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/β-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

PubMed Central

Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Masaoka, Tomokazu; Xuetao, Wei; Yoshii, Toshitaka; Horie, Masaki; Yasuda, Hiroaki; Uemura, Toshimasa; Okawa, Atsushi; Sotome, Shinichi

2015-01-01

We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. PMID:25659106

Sedimentation rates in the marshes of Sand Lake National Wildlife Refuge

USGS Publications Warehouse

Gleason, R.A.; Euliss, N.H.; Holmes, C.W.

2003-01-01

Impoundments located within river systems in the Northern Great Plains are vulnerable to sediment inputs because intensive agriculture in watersheds has increased soil erosion and sediments in rivers. At the request of the U.S. Fish and Wildlife Service (FWS), we evaluated the vertical accretion of sediment in the Mud Lake impoundment of Sand Lake National Wildlife Refuge (NWR), Brown County, South Dakota. The Mud Lake impoundment was created in 1936 by constructing a low-head dam across the James River. We collected sediment cores from the Mud Lake impoundment during August 2000 for determination of vertical accretion rates. Accretion rates were estimated using cesium-13 7 and lead-210 isotopic dating techniques to estimate sediment accretion over the past 100 years. Accretion rates were greatest near the dam (1.3 cm yr-1) with less accretion (0.2 cm yr-1) occurring in the upper reaches of Mud Lake. As expected, accretion was highest near the dam where water velocities and greater water depth facilitates sediment deposition. Higher rates of sedimentation (accretion> 2.0 cm year-1) occurred during the 1990s when river flows were especially high. Since 1959, sediment accretion has reduced maximum pool depth of Mud Lake near the dam by 55 cm. Assuming that sediment accretion rates remain the same in the future, we project Mud Lake will have a maximum pool depth of 77 and 51 cm by 2020 and 2040, respectively. Over this same time frame, water depths in the upper reaches of Mud Lake would be reduced to< 2 cm. Projected future loss of water depth will severely limit the ability of managers to manipulate pool levels in Mud Lake to cycle vegetation and create interspersion of cover and water to meet current wildlife habitat management objectives. As predicted for major dams constructed on rivers throughout the world, Mud Lake will have a finite life span. Our data suggests that the functional life span of Mud Lake since construction will be < 100 years. We anticipate that over the next 20 years, sediments entering Mud Lake will reduce water depths to the point that current wildlife management objectives cannot be achieved through customary water-level manipulations. Sedimentation impacts are not unique to the Sand Lake NWR. It is widely accepted that impoundments trap sediments and shallow impoundments, such as those managed by the FWS, are especially vulnerable. Given the ecological impacts associated with loss of water depths, we recommend that managers begin evaluating the long-term wildlife management goals for the refuge relative to associated costs and feasibility of options available to enhance and maximize the life span of existing impoundments, including upper watershed management.

Effect of bone sialoprotein coating of ceramic and synthetic polymer materials on in vitro osteogenic cell differentiation and in vivo bone formation.

PubMed

Schaeren, Stefan; Jaquiéry, Claude; Wolf, Francine; Papadimitropoulos, Adam; Barbero, Andrea; Schultz-Thater, Elke; Heberer, Michael; Martin, Ivan

2010-03-15

In this study, we addressed whether Bone Sialoprotein (BSP) coating of various substrates could enhance the in vitro osteogenic differentiation and in vivo bone formation capacity of human Bone Marrow Stromal Cells (BMSC). Moreover, we tested whether synthetic polymer-based porous scaffolds, despite the absence of a mineral component, could support ectopic bone formation by human BMSC if coated with BSP. Adsorption of recombinant human BSP on tissue culture-treated polystyrene (TCTP), beta-tricalcium phosphate (Osteologic) or synthetic polymer (Polyactive) substrates was dose dependent, but did not consistently accelerate or enhance in vitro BMSC osteogenic differentiation, as assessed by the mRNA expression of osteoblast-related genes. Similarly, BSP coating of porous beta-tricalcium phosphate scaffolds (Skelite) did not improve the efficiency of bone tissue formation following loading with BMSC and ectopic implantation in nude mice. Finally, Polyactive foams seeded with BMSC did not form bone tissue in the same ectopic assay, even if coated with BSP. We conclude that BSP coating of a variety of substrates is not directly associated with an enhancement of osteoprogenitor cell differentiation in vitro or in vivo, and that presentation of BSP on polymeric materials is not sufficient to prime BMSC functional osteoblastic differentiation in vivo. (c) 2009 Wiley Periodicals, Inc.

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

PubMed

Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

2012-03-01

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

The MRI appearances of cancellous allograft bone chips after the excision of bone tumours.

PubMed

Kang, S; Han, I; Hong, S H; Cho, H S; Kim, W; Kim, H-S

2015-01-01

Cancellous allograft bone chips are commonly used in the reconstruction of defects in bone after removal of benign tumours. We investigated the MRI features of grafted bone chips and their change over time, and compared them with those with recurrent tumour. We retrospectively reviewed 66 post-operative MRIs from 34 patients who had undergone curettage and grafting with cancellous bone chips to fill the defect after excision of a tumour. All grafts showed consistent features at least six months after grafting: homogeneous intermediate or low signal intensities with or without scattered hyperintense foci (speckled hyperintensities) on T1 images; high signal intensities with scattered hypointense foci (speckled hypointensities) on T2 images, and peripheral rim enhancement with or without central heterogeneous enhancements on enhanced images. Incorporation of the graft occurred from the periphery to the centre, and was completed within three years. Recurrent lesions consistently showed the same signal intensities as those of pre-operative MRIs of the primary lesions. There were four misdiagnoses, three of which were chondroid tumours. We identified typical MRI features and clarified the incorporation process of grafted cancellous allograft bone chips. The most important characteristics of recurrent tumours were that they showed the same signal intensities as the primary tumours. It might sometimes be difficult to differentiate grafted cancellous allograft bone chips from a recurrent chondroid tumour. ©2015 The British Editorial Society of Bone & Joint Surgery.

Mechanical loading, damping, and load-driven bone formation in mouse tibiae.

PubMed

Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki

2012-10-01

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. Copyright © 2012 Elsevier Inc. All rights reserved.

Bioactive borate glass promotes the repair of radius segmental bone defects by enhancing the osteogenic differentiation of BMSCs.

PubMed

Zhang, Jieyuan; Guan, Junjie; Zhang, Changqing; Wang, Hui; Huang, Wenhai; Guo, Shangchun; Niu, Xin; Xie, Zongping; Wang, Yang

2015-11-20

Bioactive borate glass (BG) has emerged as a promising alternative for bone regeneration due to its high osteoinductivity, osteoconductivity, compressive strength, and biocompatibility. However, the role of BG in large segmental bone repair is unclear and little is known about the underlying mechanism of BG's osteoinductivity. In this study, we demonstrated that BG possessed pro-osteogenic effects in an experimental model of critical-sized radius defects. Transplanting BG to radius defects resulted in better repair of bone defects as compared to widely used β-TCP. Histological and morphological analysis indicated that BG significantly enhanced new bone formation. Furthermore, the degradation rate of the BG was faster than that of β-TCP, which matched the higher bone regeneration rate. In addition, ions from BG enhanced cell viability, ALP activity, and osteogenic-related genes expression. Mechanistically, the critical genes Smad1/5 and Dlx5 in the BMP pathway and p-Smad1/5 proteins were significantly elevated after BG transplantation, and these effects could be blocked by the BMP/Smad specific inhibitor. Taken together, our findings suggest that BG could repair large segmental bone defects through activating the BMP/Smad pathway and osteogenic differentiation in BMSCs.

Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia.

PubMed

Liu, Wei-Chung; Chuang, Wei-Ling; Tsai, Min-Lung; Hong, Ji-Hong; McBride, William H; Chiang, Chi-Shiun

2008-04-01

This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment. Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase-positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-kappaB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.

Enhancement of bone consolidation in mandibular distraction osteogenesis: a contemporary review of experimental studies involving adjuvant therapies.

PubMed

Hong, Paul; Boyd, Daniel; Beyea, Steven D; Bezuhly, Michael

2013-07-01

One of the major disadvantages of mandibular distraction osteogenesis (MDO) is the prolonged time required for consolidation of the regenerate bone. The objective of the present study is to perform a contemporary review of various adjuvant therapies to enhance bone consolidation in MDO. A PubMed search for articles related to MDO, along with the references of those articles, was performed. Inclusion and exclusion criteria were applied to all experimental studies assessing adjuvant therapies to enhance bone consolidation. A total of 1414 titles and abstracts were initially reviewed; 61 studies were included for full review. Many studies involved growth factors, hormones, pharmacological agents, gene therapy, and stem cells. Other adjuvant therapies included mechanical stimulation, laser therapy, and hyperbaric oxygen. Majority of the studies demonstrated positive bone healing effects and thus adjuvant therapies remain a viable strategy to enhance and hasten the consolidation period. Although most studies have demonstrated promising results, many questions still remain, such as optimal amount, timing, and delivery methods required to stimulate the most favorable bone regeneration. As well, further studies comparing various adjuvant therapies and documentation of long-term adverse effects are required prior to clinical application. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Formononetin, a methoxy isoflavone, enhances bone regeneration in a mouse model of cortical bone defect.

PubMed

Singh, Krishna Bhan; Dixit, Manisha; Dev, Kapil; Maurya, Rakesh; Singh, Divya

2017-06-01

The bone regeneration and healing effect of formononetin was evaluated in a cortical bone defect model that predominantly heals by intramembranous ossification. For this study, female Balb/c mice were ovariectomised (OVx) and a drill-hole injury was generated in the midfemoral bones of all animals. Treatment with formononetin commenced the day after and continued for 21 d. Parathyroid hormone (PTH1-34) was used as a reference standard. Animals were killed at days 10 and 21. Femur bones were collected at the injury site for histomorphometry studies using microcomputed tomography (μCT) and confocal microscopy. RNA and protein were harvested from the region surrounding the drill-hole injury. For immunohistochemistry, 5 µm sections of decalcified femur bone adjoining the drill-hole site were cut. μCT analysis showed that formononetin promoted bone healing at days 10 and 21 and the healing effect observed was significantly better than in Ovx mice and equal to PTH treatment in many aspects. Formononetin also significantly enhanced bone regeneration as assessed by calcein-labelling studies. In addition, formononetin enhanced the expression of osteogenic markers at the injury site in a manner similar to PTH. Formononetin treatment also led to predominant runt-related transcription factor 2 and osteocalcin localisation at the injury site. These results support the potential of formononetin to be a bone-healing agent and are suggestive of its promising role in the fracture-repair process.

Holocene reef accretion: southwest Molokai, Hawaii, U.S.A.

USGS Publications Warehouse

Engels, Mary S.; Fletcher, Charles H.; Field, Michael E.; Storlazzi, Curt D.; Grossman, Eric E.; Rooney, John J.B.; Conger, Christopher L.; Glenn, Craig

2004-01-01

Two reef systems off south Molokai, Hale O Lono and Hikauhi (separated by only 10 km), show strong and fundamental differences in modern ecosystem structure and Holocene accretion history that reflect the influence of wave-induced near-bed shear stresses on reef development in Hawaii. Both sites are exposed to similar impacts from south, Kona, and trade-wind swell. However, the Hale O Lono site is exposed to north swell and the Hikuahi site is not. As a result, the reef at Hale O Lono records no late Holocene net accretion while the reef at Hikauhi records consistent and robust accretion over late Holocene time. Analysis and dating of 24 cores from Hale O Lono and Hikauhi reveal the presence of five major lithofacies that reflect paleo-environmental conditions. In order of decreasing depositional energy they are: (1) coral-algal bindstone; (2) mixed skeletal rudstone; (3) massive coral framestone; (4) unconsolidated floatstone; and (5) branching coral framestone-bafflestone. At Hale O Lono, 10 cores document a backstepping reef ranging from ∼ 8,100 cal yr BP (offshore) to ∼ 4,800 cal yr BP (nearshore). A depauperate community of modern coral diminishes shoreward and seaward of ∼ 15 m depth due to wave energy, disrupted recruitment activities, and physical abrasion. Evidence suggests a change from conditions conducive to accretion during the early Holocene to conditions detrimental to accretion in the late Holocene. Reef structure at Hikauhi, reconstructed from 14 cores, reveals a thick, rapidly accreting and young reef (maximum age ∼ 900 cal yr BP). Living coral cover on this reef increases seaward with distance from the reef crest but terminates at a depth of ∼ 20 m where the reef ends in a large sand field. The primary limitation on vertical reef growth is accommodation space under wave base, not recruitment activities or energy conditions. Interpretations of cored lithofacies suggest that modern reef growth on the southwest corner of Molokai, and by extension across Hawaii in general, is controlled by wave-induced near-bed shear stress related to refracted North Pacific swell. Holocene accretion patterns here also reflect the long-term influence of wave-induced near-bed shear stress from north swell during late Holocene time. This finding is consistent with other studies (e.g., Grigg 1998; Cabioch et al. 1999) that reflect the dominance of swell energy and sea level in controlling modern and late Holocene accretion elsewhere in Hawaii and across the Pacific and Indian oceans. Notably, however, this result is refined and clarified for Hawaii in the hypothesis of Rooney et al. (2003) stating that enhancement of the El Niño Southern Oscillation beginning approximately 5000 years ago led to increased north swell energy and signaled the end to net accretion along exposed coastlines in Hawaii. The exposure of Hale O Lono to north swell and the age of sea floor there (ca. 4,800 cal yr BP), coupled with the lack of north swell incidence at Hikauhi and the continuous accretion that has occurred there over the last millennium, strongly supports the ENSO reef hypothesis as outlined by Rooney et al. (2003). Other factors controlling Holocene reef accretion at the study site are relative sea-level position and rate of rise, and wave sheltering by Laau Point. Habitat suitable for reef accretion on the southwest shore of Molokai has shrunk throughout the Holocene.

Cytokines TNF-α, IL-6, IL-17F, and IL-4 Differentially Affect Osteogenic Differentiation of Human Adipose Stem Cells

PubMed Central

Bravenboer, Nathalie

2016-01-01

During the initial stages of bone repair, proinflammatory cytokines are released within the injury site, quickly followed by a shift to anti-inflammatory cytokines. The effect of pro- and anti-inflammatory cytokines on osteogenic differentiation of mesenchymal stem cells is controversial. Here, we investigated the effect of the proinflammatory cytokines TNF-α, IL-6, IL-8, and IL-17F and the anti-inflammatory cytokine IL-4 on proliferation and osteogenic differentiation of human adipose stem cells (hASCs). hASCs were treated with TNF-α, IL-6, IL-8, IL-17F, or IL-4 (10 ng/mL) for 72 h mimicking bone repair. TNF-α reduced collagen type I gene expression but increased hASC proliferation and ALP activity. IL-6 also strongly enhanced ALP activity (18-fold), as well as bone nodule formation by hASCs. IL-8 did not affect proliferation or osteogenic gene expression but reduced bone nodule formation. IL-17F decreased hASC proliferation but enhanced ALP activity. IL-4 enhanced osteocalcin gene expression and ALP activity but reduced RUNX2 gene expression and bone nodule formation. In conclusion, all cytokines studied have both enhancing and reducing effects on osteogenic differentiation of hASCs, even when applied for 72 h only. Some cytokines, specifically IL-6, may be suitable to induce osteogenic differentiation of mesenchymal stem cells as a strategy for enhancing bone repair. PMID:27667999

Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

PubMed

Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

2015-10-01

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

COMPLEX VARIABILITY OF THE H{alpha} EMISSION LINE PROFILE OF THE T TAURI BINARY SYSTEM KH 15D: THE INFLUENCE OF ORBITAL PHASE, OCCULTATION BY THE CIRCUMBINARY DISK, AND ACCRETION PHENOMENA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, Catrina M.; Johns-Krull, Christopher M.; Mundt, Reinhard

2012-06-01

We have obtained 48 high-resolution echelle spectra of the pre-main-sequence eclipsing binary system KH 15D (V582 Mon, P = 48.37 days, e {approx} 0.6, M{sub A} = 0.6 M{sub Sun }, M{sub B} = 0.7 M{sub Sun }). The eclipses are caused by a circumbinary disk (CBD) seen nearly edge on, which at the epoch of these observations completely obscured the orbit of star B and a large portion of the orbit of star A. The spectra were obtained over five contiguous observing seasons from 2001/2002 to 2005/2006 while star A was fully visible, fully occulted, and during several ingressmore » and egress events. The H{alpha} line profile shows dramatic changes in these time series data over timescales ranging from days to years. A fraction of the variations are due to 'edge effects' and depend only on the height of star A above or below the razor sharp edge of the occulting disk. Other observed variations depend on the orbital phase: the H{alpha} emission line profile changes from an inverse P-Cygni-type profile during ingress to an enhanced double-peaked profile, with both a blue and a red emission component, during egress. Each of these interpreted variations are complicated by the fact that there is also a chaotic, irregular component present in these profiles. We find that the complex data set can be largely understood in the context of accretion onto the stars from a CBD with gas flows as predicted by the models of eccentric T Tauri binaries put forward by Artymowicz and Lubow, Guenther and Kley, and de Val-Borro et al. In particular, our data provide strong support for the pulsed accretion phenomenon, in which enhanced accretion occurs during and after perihelion passage.« less

In vitro and in vivo evaluation of MgF2 coated AZ31 magnesium alloy porous scaffolds for bone regeneration.

PubMed

Yu, Weilin; Zhao, Huakun; Ding, Zhenyu; Zhang, Zhiwang; Sun, Benben; Shen, Ji; Chen, Shanshan; Zhang, Bingchun; Yang, Ke; Liu, Meixia; Chen, Daoyun; He, Yaohua

2017-01-01

Porous magnesium scaffolds are attracting increasing attention because of their degradability and good mechanical property. In this work, a porous and degradable AZ31 magnesium alloy scaffold was fabricated using laser perforation technique. To enhance the corrosion resistance and cytocompatibility of the AZ31 scaffolds, a fluoride treatment was used to acquire the MgF 2 coating. Enhanced corrosion resistance was confirmed by immersion and electrochemical tests. Due to the protection provided by the MgF 2 coating, the magnesium release and pH increase resulting from the degradation of the FAZ31 scaffolds were controllable. Moreover, in vitro studies revealed that the MgF 2 coated AZ31 (FAZ31) scaffolds enhanced the proliferation and attachment of rat bone marrow stromal cells (rBMSCs) compared with the AZ31 scaffolds. In addition, our present data indicated that the extract of the FAZ31 scaffold could enhance the osteogenic differentiation of rBMSCs. To compare the in vivo bone regenerative capacity of the AZ31 and FAZ31 scaffolds, a rabbit femoral condyle defect model was used. Micro-computed tomography (micro-CT) and histological examination were performed to evaluate the degradation of the scaffolds and bone volume changes. In addition to the enhanced the corrosion resistance, the FAZ31 scaffolds were more biocompatible and induced significantly more new bone formation in vivo. Conversely, bone resorption was observed from the AZ31 scaffolds. These promising results suggest potential clinical applications of the fluoride pretreated AZ31 scaffold for bone tissue repair and regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

A 1.3 mm SMA survey of 29 variable young stellar objects

NASA Astrophysics Data System (ADS)

Liu, Hauyu Baobab; Dunham, Michael M.; Pascucci, Ilaria; Bourke, Tyler L.; Hirano, Naomi; Longmore, Steven; Andrews, Sean; Carrasco-González, Carlos; Forbrich, Jan; Galván-Madrid, Roberto; Girart, Josep M.; Green, Joel D.; Juárez, Carmen; Kóspál, Ágnes; Manara, Carlo F.; Palau, Aina; Takami, Michihiro; Testi, Leonardo; Vorobyov, Eduard I.

2018-04-01

Context. Young stellar objects (YSOs) may undergo periods of active accretion (outbursts), during which the protostellar accretion rate is temporarily enhanced by a few orders of magnitude. Whether or not these accretion outburst YSOs possess similar dust and gas reservoirs to each other, and whether or not their dust and gas reservoirs are similar as quiescent YSOs, are issues yet to be clarified. Aims: The aim of this work is to characterize the millimeter thermal dust emission properties of a statistically significant sample of long and short duration accretion outburst YSOs (i.e., FUors and EXors) and the spectroscopically identified candidates of accretion outbursting YSOs (i.e., FUor-like objects). Methods: We have carried out extensive Submillimeter Array (SMA) observations mostly at 225 GHz (1.33 mm) and 272 GHz (1.10 mm), from 2008 to 2017. We covered accretion outburst YSOs located at <1 kpc distances from the solar system. Results: We analyze all the existing SMA data of such objects, both published and unpublished, in a coherent way to present a millimeter interferometric database of 29 objects. We obtained 21 detections at >3σ significance. Detected sources except for the two cases of V883 Ori and NGC 2071 MM3 were observed with 1″ angular resolution. Overall our observed targets show a systematically higher millimeter luminosity distribution than those of the M* > 0.3 M⊙ Class II YSOs in the nearby (≲400 pc) low-mass star-forming molecular clouds (e.g., Taurus, Lupus, Upp Scorpio, and Chameleon I). In addition, at 1 mm our observed confirmed binaries or triple-system sources are systematically fainter than the rest of the sources even though their 1 mm fluxes are broadly distributed. We may have detected 30-60% millimeter flux variability from V2494 Cyg and V2495 Cyg, from the observations separated by approximately one year.

White Dwarf/M Dwarf Binaries as Single Degenerate Progenitors of Type Ia Supernovae

NASA Astrophysics Data System (ADS)

Wheeler, J. Craig

2012-10-01

Limits on the companions of white dwarfs in the single-degenerate scenario for the origin of Type Ia supernovae (SNe Ia) have gotten increasingly tight, yet igniting a nearly Chandrasekhar mass C/O white dwarf from a condition of near hydrostatic equilibrium provides compelling agreement with observed spectral evolution. The only type of non-degenerate stars that survive the tight limits, MV >~ 8.4 on the SN Ia in SNR 0509-67.5 and MV >~ 9.5 in the remnant of SN 1572, are M dwarfs. While M dwarfs are observed in cataclysmic variables, they have special properties that have not been considered in most work on the progenitors of SNe Ia: they have small but finite magnetic fields and they flare frequently. These properties are explored in the context of SN Ia progenitors. White dwarf/M dwarf pairs may be sufficiently plentiful to provide, in principle, an adequate rate of explosions even with slow orbital evolution due to magnetic braking or gravitational radiation. Even modest magnetic fields on the white dwarf and M dwarf will yield adequate torques to lock the two stars together, resulting in a slowly rotating white dwarf, with the magnetic poles pointing at one another in the orbital plane. The mass loss will be channeled by a "magnetic bottle" connecting the two stars, landing on a concentrated polar area on the white dwarf. This enhances the effective rate of accretion compared to spherical accretion. Luminosity from accretion and hydrogen burning on the surface of the white dwarf may induce self-excited mass transfer. The combined effects of self-excited mass loss, polar accretion, and magnetic inhibition of mixing of accretion layers give possible means to beat the "nova limit" and grow the white dwarf to the Chandrasekhar mass even at rather moderate mass accretion rates.

The intensity of physical activity influences bone mineral accrual in childhood: the childhood health, activity and motor performance school (the CHAMPS) study, Denmark.

PubMed

Heidemann, Malene; Mølgaard, Christian; Husby, Steffen; Schou, Anders J; Klakk, Heidi; Møller, Niels Chr; Holst, René; Wedderkopp, Niels

2013-03-02

Studies indicate genetic and lifestyle factors can contribute to optimal bone development. In particular, the intensity level of physical activity may have an impact on bone health. This study aims to assess the relationship between physical activity at different intensities and Bone Mineral Content (BMC), Bone Mineral Density (BMD) and Bone Area (BA) accretion. This longitudinal study is a part of The CHAMPS study-DK. Whole-body DXA scans were performed at baseline and after two years follows up. BMC, BMD, and BA were measured. The total body less head (TBLH) values were used. Physical activity (PA) was recorded by accelerometers (ActiGraph, model GT3X). Percentages of different PA intensity levels were calculated and log odds of two intensity levels of activity relative to the third level were calculated. Multilevel regression analyses were used to assess the relationship between the categories of physical activity and bone traits. Of 800 invited children, 742 (93%) accepted to participate. Of these, 682/742 (92%) participated at follow up. Complete datasets were obtained in 602/742 (81%) children. Mean (range) of age was 11.5 years (9.7-13.9). PA at different intensity levels was for boys and girls respectively, sedentary 62% and 64%, low 29% for both genders and moderate to high 9% and 7% of the total time. Mean (range) BMC, BMD, and BA was 1179 g (563-2326), 0.84 g/cm2 (0.64-1.15) and 1393 cm2 (851-2164), respectively. Valid accelerometer data were obtained for a mean of 6.1 days, 13 hours per day. There 7was a positive relationship between the log odds of moderate to high-level PA versus low level activity and BMC, BMD and BA. Children with an increased proportion of time in moderate to high-level activity as opposed to sedentary and low-level activity achieved positive effects on BMC, BMD and BA.

A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius.

PubMed

Chesi, Alessandra; Mitchell, Jonathan A; Kalkwarf, Heidi J; Bradfield, Jonathan P; Lappe, Joan M; McCormack, Shana E; Gilsanz, Vicente; Oberfield, Sharon E; Hakonarson, Hakon; Shepherd, John A; Kelly, Andrea; Zemel, Babette S; Grant, Struan F A

2015-09-01

Childhood fractures are common, with the forearm being the most common site. Genome-wide association studies (GWAS) have identified more than 60 loci associated with bone mineral density (BMD) in adults but less is known about genetic influences specific to bone in childhood. To identify novel genetic factors that influence pediatric bone strength at a common site for childhood fractures, we performed a sex-stratified trans-ethnic genome-wide association study of areal BMD (aBMD) and bone mineral content (BMC) Z-scores measured by dual energy X-ray absorptiometry at the one-third distal radius, in a cohort of 1399 children without clinical abnormalities in bone health. We tested signals with P < 5 × 10(-6) for replication in an independent, same-age cohort of 486 Caucasian children. Two loci yielded a genome-wide significant combined P-value: rs7797976 within CPED1 in females [P = 2.4 × 10(-11), β =- 0.30 standard deviations (SD) per T allele; aBMD-Z] and rs7035284 at 9p21.3 in males (P = 1.2 × 10(-8), β = 0.28 SD per G allele; BMC-Z). Signals at the CPED1-WNT16-FAM3C locus have been previously associated with BMD at other skeletal sites in adults and children. Our result at the distal radius underscores the importance of this locus at multiple skeletal sites. The 9p21.3 locus is within a gene desert, with the nearest gene flanking each side being MIR31HG and MTAP, neither of which has been implicated in BMD or BMC previously. These findings suggest that genetic determinants of childhood bone accretion at the radius, a skeletal site that is primarily cortical bone, exist and also differ by sex. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Commensal Microbiota Enhance Both Osteoclast and Osteoblast Activities.

PubMed

Uchida, Yoko; Irie, Koichiro; Fukuhara, Daiki; Kataoka, Kota; Hattori, Takako; Ono, Mitsuaki; Ekuni, Daisuke; Kubota, Satoshi; Morita, Manabu

2018-06-23

Recent studies suggest that the commensal microbiota affects not only host energy metabolism and development of immunity but also bone remodeling by positive regulation of osteoclast activity. However, the mechanism of regulation of bone cells by the commensal microbiota has not been elucidated. In this study, 8-week-old specific pathogen-free (SPF) and germ-free (GF) mice were compared in terms of alveolar bones and primary osteoblasts isolated from calvarias. Micro-CT analysis showed that SPF mice had larger body size associated with lower bone mineral density and bone volume fraction in alveolar bones compared with GF mice. Greater numbers of osteoclasts in alveolar bone and higher serum levels of tartrate-resistant acid phosphatase 5b were observed in SPF mice. Tissue extracts from SPF alveolar bone showed higher levels of cathepsin K, indicating higher osteoclast activity. SPF alveolar extracts also showed elevated levels of γ-carboxylated glutamic acid⁻osteocalcin as a marker of mature osteoblasts compared with GF mice. Polymerase chain reaction (PCR) array analysis of RNA directly isolated from alveolar bone showed that in SPF mice, expression of mRNA of osteocalcin , which also acts as an inhibitor of bone mineralization, was strongly enhanced compared with GF mice. Cultured calvarial osteoblasts from SPF mice showed reduced mineralization but significantly enhanced expression of mRNAs of osteocalcin, alkaline phosphatase, insulin-like growth factor-I/II , and decreased ratio of osteoprotegerin/receptor activator of nuclear factor-kappa B ligand compared with GF mice. Furthermore, PCR array analyses of transcription factors in cultured calvarial osteoblasts showed strongly upregulated expression of Forkhead box g1 . In contrast, Gata-binding protein 3 was strongly downregulated in SPF osteoblasts. These results suggest that the commensal microbiota prevents excessive mineralization possibly by stimulating osteocalcin expression in osteoblasts, and enhances both osteoblast and osteoclast activity by regulating specific transcription factors.

Targeting skeletal endothelium to ameliorate bone loss.

PubMed

Xu, Ren; Yallowitz, Alisha; Qin, An; Wu, Zhuhao; Shin, Dong Yeon; Kim, Jung-Min; Debnath, Shawon; Ji, Gang; Bostrom, Mathias P; Yang, Xu; Zhang, Chao; Dong, Han; Kermani, Pouneh; Lalani, Sarfaraz; Li, Na; Liu, Yifang; Poulos, Michael G; Wach, Amanda; Zhang, Yi; Inoue, Kazuki; Di Lorenzo, Annarita; Zhao, Baohong; Butler, Jason M; Shim, Jae-Hyuck; Glimcher, Laurie H; Greenblatt, Matthew B

2018-06-01

Recent studies have identified a specialized subset of CD31 hi endomucin hi (CD31 hi EMCN hi ) vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31 hi EMCN hi endothelium levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of Shn3, which have markedly elevated bone formation, demonstrated an increase in CD31 hi EMCN hi endothelium. Transcriptomic analysis identified SLIT3 as an osteoblast-derived, SHN3-regulated proangiogenic factor. Genetic deletion of Slit3 reduced skeletal CD31 hi EMCN hi endothelium, resulted in low bone mass because of impaired bone formation and partially reversed the high bone mass phenotype of Shn3 -/- mice. This coupling between osteoblasts and CD31 hi EMCN hi endothelium is essential for bone healing, as shown by defective fracture repair in SLIT3-mutant mice and enhanced fracture repair in SHN3-mutant mice. Finally, administration of recombinant SLIT3 both enhanced bone fracture healing and counteracted bone loss in a mouse model of postmenopausal osteoporosis. Thus, drugs that target the SLIT3 pathway may represent a new approach for vascular-targeted osteoanabolic therapy to treat bone loss.

Implosive accretion and outbursts of active galactic nuclei

NASA Technical Reports Server (NTRS)

Lovelace, R. V. E.; Romanova, M. M.; Newman, W. I.

1994-01-01

A model and simulation code have been developed for time-dependent axisymmetric disk accretion onto a compact object including for the first time the influence of an ordered magnetic field. The accretion rate and radiative luminosity of the disk are naturally coupled to the rate of outflow of energy and angular momentum in magnetically driven (+/- z) winds. The magnetic field of the wind is treated in a phenomenological way suggested by self-consistent wind solutions. The radial accretion speed u(r, t) of the disk matter is shown to be the sum of the usual viscous contribution and a magnetic contribution proportional to r(exp 3/2)(B(sub p exp 2))/sigma, where B(sub p)(r,t) is the poloidal field threading the disk and sigma(r,t) is the disk's surface mass density. An enhancement or variation in B(sub p) at a large radial distance leads to the formation of a soliton-like structure in the disk density, temperature, and B-field which propagates implosively inward. The implosion gives a burst in the power output in winds or jets and a simultaneous burst in the disk radiation. The model is pertinent to the formation of discrete fast-moving components in jets observed by very long baseline interferometry. These components appear to originate at times of optical outbursts of the active galactic nucleus.

Long-orbital-period Prepolars Containing Early K-type Donor Stars. Bottleneck Accretion Mechanism in Action

NASA Astrophysics Data System (ADS)

Tovmassian, G.; González–Buitrago, D.; Zharikov, S.; Reichart, D. E.; Haislip, J. B.; Ivarsen, K. M.; LaCluyze, A. P.; Moore, J. P.; Miroshnichenko, A. S.

2016-03-01

We studied two objects identified as cataclysmic variables (CVs) with periods exceeding the natural boundary for Roche-lobe-filling zero-age main sequence (ZAMS) secondary stars. We present observational results for V1082 Sgr with a 20.82 hr orbital period, an object that shows a low luminosity state when its flux is totally dominated by a chromospherically active K star with no signs of ongoing accretion. Frequent accretion shutoffs, together with characteristics of emission lines in a high state, indicate that this binary system is probably detached, and the accretion of matter on the magnetic white dwarf takes place through stellar wind from the active donor star via coupled magnetic fields. Its observational characteristics are surprisingly similar to V479 And, a 14.5 hr binary system. They both have early K-type stars as donor stars. We argue that, similar to the shorter-period prepolars containing M dwarfs, these are detached binaries with strong magnetic components. Their magnetic fields are coupled, allowing enhanced stellar wind from the K star to be captured and channeled through the bottleneck connecting the two stars onto the white dwarf’s magnetic pole, mimicking a magnetic CV. Hence, they become interactive binaries before they reach contact. This will help to explain an unexpected lack of systems possessing white dwarfs with strong magnetic fields among detached white+red dwarf systems.

Sclerostin Antibody Treatment Enhances Rotator Cuff Tendon-to-Bone Healing in an Animal Model.

PubMed

Shah, Shivam A; Kormpakis, Ioannis; Havlioglu, Necat; Ominsky, Michael S; Galatz, Leesa M; Thomopoulos, Stavros

2017-05-17

Rotator cuff tears are a common source of pain and disability, and poor healing after repair leads to high retear rates. Bone loss in the humeral head before and after repair has been associated with poor healing. The purpose of the current study was to mitigate bone loss near the repaired cuff and improve healing outcomes. Sclerostin antibody (Scl-Ab) treatment, previously shown to increase bone formation and strength in the setting of osteoporosis, was used in the current study to address bone loss and enhance rotator cuff healing in an animal model. Scl-Ab was administered subcutaneously at the time of rotator cuff repair and every 2 weeks until the animals were sacrificed. The effect of Scl-Ab treatment was evaluated after 2, 4, and 8 weeks of healing, using bone morphometric analysis, biomechanical evaluation, histological analysis, and gene expression outcomes. Injury and repair led to a reduction in bone mineral density after 2 and 4 weeks of healing in the control and Scl-Ab treatment groups. After 8 weeks of healing, animals receiving Scl-Ab treatment had 30% greater bone mineral density than the controls. A decrease in biomechanical properties was observed in both groups after 4 weeks of healing compared with healthy tendon-to-bone attachments. After 8 weeks of healing, Scl-Ab-treated animals had improved strength (38%) and stiffness (43%) compared with control animals. Histological assessment showed that Scl-Ab promoted better integration of tendon and bone by 8 weeks of healing. Scl-Ab had significant effects on gene expression in bone, indicative of enhanced bone formation, and no effect on the expression of genes in tendon. This study provides evidence that Scl-Ab treatment improves tendon-to-bone healing at the rotator cuff by increasing attachment-site bone mineral density, leading to improved biomechanical properties. Scl-Ab treatment may improve outcomes after rotator cuff repair.

Orexin Regulates Bone Remodeling via a Dominant Positive Central Action and a Subordinate Negative Peripheral Action

PubMed Central

Wei, Wei; Motoike, Toshiyuki; Krzeszinski, Jing Y.; Jin, Zixue; Xie, Xian-Jin; Dechow, Paul C.; Yanagisawa, Masashi; Wan, Yihong

2014-01-01

SUMMARY Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R-null mice exhibit low-bone-mass owing to elevated circulating leptin; whereas central administration of an OX2R-selective agonist augments bone mass. Conversely, orexin also functions peripherally through orexin receptor 1 (OX1R) in the bone to suppress bone formation. OX1R-null mice exhibit high-bone-mass owing to a mesenchymal stem cell differentiation shift from adipocyte to osteoblast that results from higher osseous ghrelin expression. The central action is dominant over the peripheral action because bone mass is reduced in orexin-null and OX1R2R-double-null mice but enhanced in orexin over-expressing transgenic mice. These findings reveal orexin as a critical rheostat of skeletal homeostasis that exerts a yin-yang dual regulation, and highlight orexin as a therapeutic target for osteoporosis. PMID:24794976

Deletion of the distal Tnfsf11 RL-D2 enhancer that contributes to PTH-mediated RANKL expression in osteoblast lineage cells results in a high bone mass phenotype in mice

PubMed Central

Onal, M.; St John, H.C.; Danielson, A.L.; Pike, J.W.

2016-01-01

Receptor activator of nuclear factor-κB ligand (RANKL) is a TNF-like cytokine that is necessary for osteoclast formation and survival. Elevated RANKL synthesis is associated with both increased osteoclast number and bone resorption. Earlier studies identified an enhancer 76 kb upstream of the Tnfsf11 transcriptional start site (TSS) termed RL-D5 or the distal control region (DCR) that modulates RANKL expression in response to PTH, 1,25(OH)2D3, and an array of cytokines. Mice lacking RL-D5 exhibit high bone mass associated with decreased RANKL expression in bone, spleen, and thymus. In addition to RL-D5, genome-wide studies have identified 9 additional Tnfsf11 enhancers residing upstream of the gene’s TSS, which provide RANKL cell type-specificity and responsiveness to local and systemic factors. ChIP-chip analysis has revealed inducible VDR and CREB binding at an enhancer termed RL-D2 23 kb upstream of the Tnfsf11 TSS in osteoblastic ST2 cells. Herein, we use ChIP-seq analysis to confirm this finding and delete this enhancer from the mouse genome to determine its physiological role in vivo. RL-D2−/− primary stromal cells showed decreased RANKL-induction by both forskolin and 1,25(OH)2D3 ex vivo. Consistent with this, the PTH induction of RANKL expression was significantly blunted in RL-D2−/− mice in vivo. In contrast, lack of RL-D2 had no effect on 1,25(OH)2D3 induction of RANKL in vivo. Similar to the results seen in RL-D5−/− mice, lack of RL-D2 led to decreased skeletal RANKL expression, resulting in decreased osteoclast numbers and a progressive increase in bone mineral density. Lack of RL-D2 increased cancellous bone mass in femur and spine, but did not alter femoral cortical bone thickness. These results highlight the role of distal enhancers in the regulation of RANKL expression by PTH and perhaps 1,25(OH)2D3, and suggest that the RL-D2 and RL-D5 enhancers contribute in either an additive or synergistic manner to regulate bone remodeling. PMID:26332516

Dietary phlorizin enhances osteoblastogenic bone formation through enhancing β-catenin activity via GSK-3β inhibition in a model of senile osteoporosis.

PubMed

Antika, Lucia Dwi; Lee, Eun-Jung; Kim, Yun-Ho; Kang, Min-Kyung; Park, Sin-Hye; Kim, Dong Yeon; Oh, Hyeongjoo; Choi, Yean-Jung; Kang, Young-Hee

2017-11-01

Osteoporosis is one of the most prevalent forms of age-related bone diseases. Increased bone loss with advancing age has become a grave public health concern. This study examined whether phlorizin and phloretin, dihydrochalcones in apple peels, inhibited senile osteoporosis through enhancing osteoblastogenic bone formation in cell-based and aged mouse models. Submicromolar phloretin and phlorizin markedly stimulated osteoblast differentiation of MC3T3-E1 cells with increased transcription of Runx2 and osteocalcin. Senescence-accelerated resistant mouse strain prone-6 (SAMP6) mice were orally supplemented with 10 mg/kg phlorizin and phloretin daily for 12 weeks. Male senescence-accelerated resistant mouse strain R1 mice were employed as a nonosteoporotic age-matched control. Oral administration of ploretin and phorizin boosted bone mineralization in all the bones of femur, tibia and vertebra of SAMP6. In particular, phlorizin reduced serum RANKL/OPG ratio and diminished TRAP-positive osteoclasts in trabecular bones of SAMP6. Additionally, treating phlorizin to SAMP6 inhibited the osteoporotic resorption in distal femoral bones through up-regulating expression of BMP-2 and collagen-1 and decreasing production of matrix-degrading cathepsin K and MMP-9. Finally, phlorizin and phloretin antagonized GSK-3β induction and β-catenin phosphorylation in osteoblasts and aged mouse bones. Therefore, phlorizin and phloretin were potential therapeutic agents encumbering senile osteoporosis through promoting bone-forming osteoblastogenesis via modulation of GSK-3β/β-catenin-dependent signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

The combined effects of sediment accretion (burial) and nutrient enrichment on the growth and propagation of Phalaris arundinacea

PubMed Central

Chen, Xinsheng; Liao, Yulin; Xie, Yonghong; Wu, Chao; Li, Feng; Deng, Zhengmiao; Li, Xu

2017-01-01

Sediment accretion (burial) and nutrient enrichment occur concurrently in lacustrine wetlands, but the role of these two aspects of sedimentation on macrophyte performance has rarely been examined. Here, we investigated the concurrent effects of sediment accretion and nutrient enrichment on the growth and propagation of Phalaris arundinacea L. using a factorial sediment burial by nutrient addition experimental design. Regardless of burial depth, nutrient addition increased biomass accumulation, shoot mass ratio, the number of rhizomes, and the length of ramets and rhizomes. While burial had little effect on plant growth and propagation, it had an interactive effect with nutrient addition on belowground growth and ramet production. These results indicate that P. arundinacea is tolerant to burial, which allows it to grow in habitats with high sedimentation rates. However, the enhanced growth and propagation of P. arundinacea following sedimentation were primarily related to nutrient enrichment. This suggests that nutrient enrichment of sediments, which occurs in many lacustrine wetlands, increases the risk of invasion by P. arundinacea. PMID:28054590

Deletion of the Distal Tnfsf11 RL-D2 Enhancer That Contributes to PTH-Mediated RANKL Expression in Osteoblast Lineage Cells Results in a High Bone Mass Phenotype in Mice.

PubMed

Onal, Melda; St John, Hillary C; Danielson, Allison L; Pike, J Wesley

2016-02-01

Receptor activator of nuclear factor-κB ligand (RANKL) is a tumor necrosis factor (TNF)-like cytokine that is necessary for osteoclast formation and survival. Elevated RANKL synthesis is associated with both increased osteoclast number and bone resorption. Earlier studies identified an enhancer 76 kb upstream of the Tnfsf11 transcriptional start site (TSS) termed RL-D5 or the distal control region (DCR) that modulates RANKL expression in response to PTH, 1,25(OH)2D3,, and an array of cytokines. Mice lacking RL-D5 exhibit high bone mass associated with decreased RANKL expression in bone, spleen, and thymus. In addition to RL-D5, genome-wide studies have identified 9 additional Tnfsf11 enhancers residing upstream of the gene's TSS, which provide RANKL cell type-specificity and responsiveness to local and systemic factors. ChIP-chip analyses has revealed inducible vitamin D receptor (VDR) and cAMP response element-binding protein (CREB) binding at an enhancer termed RL-D2 23 kb upstream of the Tnfsf11 TSS in osteoblastic ST2 cells. Herein, we use ChIP-seq analyses to confirm this finding and then delete this enhancer from the mouse genome to determine its physiological role in vivo. RL-D2(-/-) primary stromal cells showed decreased RANKL-induction by both forskolin and 1,25(OH)2D3 ex vivo. Consistent with this, the parathyroid hormone (PTH) induction of RANKL expression was significantly blunted in RL-D2(-/-) mice in vivo. In contrast, lack of RL-D2 had no effect on 1,25(OH)2D3 induction of RANKL in vivo. Similar to the results found in RL-D5(-/-) mice, lack of RL-D2 led to decreased skeletal RANKL expression, resulting in decreased osteoclast numbers and a progressive increase in bone mineral density. Lack of RL-D2 increased cancellous bone mass in femur and spine but did not alter femoral cortical bone thickness. These results highlight the role of distal enhancers in the regulation of RANKL expression by PTH and perhaps 1,25(OH)2D3 and suggest that the RL-D2 and RL-D5 enhancers contribute in either an additive or synergistic manner to regulate bone remodeling. © 2015 American Society for Bone and Mineral Research.

High-resolution T1-weighted 3D real IR imaging of the temporal bone using triple-dose contrast material.

PubMed

Naganawa, Shinji; Koshikawa, Tokiko; Nakamura, Tatsuya; Fukatsu, Hiroshi; Ishigaki, Takeo; Aoki, Ikuo

2003-12-01

The small structures in the temporal bone are surrounded by bone and air. The objectives of this study were (a) to compare contrast-enhanced T1-weighted images acquired by fast spin-echo-based three-dimensional real inversion recovery (3D rIR) against those acquired by gradient echo-based 3D SPGR in the visualization of the enhancement of small structures in the temporal bone, and (b) to determine whether either 3D rIR or 3D SPGR is useful for visualizing enhancement of the cochlear lymph fluid. Seven healthy men (age range 27-46 years) volunteered to participate in this study. All MR imaging was performed using a dedicated bilateral quadrature surface phased-array coil for temporal bone imaging at 1.5 T (Visart EX, Toshiba, Tokyo, Japan). The 3D rIR images (TR/TE/TI: 1800 ms/10 ms/500 ms) and flow-compensated 3D SPGR images (TR/TE/FA: 23 ms/10 ms/25 degrees) were obtained with a reconstructed voxel size of 0.6 x 0.7 x 0.8 mm3. Images were acquired before and 1, 90, 180, and 270 min after the administration of triple-dose Gd-DTPA-BMA (0.3 mmol/kg). In post-contrast MR images, the degree of enhancement of the cochlear aqueduct, endolymphatic sac, subarcuate artery, geniculate ganglion of the facial nerve, and cochlear lymph fluid space was assessed by two radiologists. The degree of enhancement was scored as follows: 0 (no enhancement); 1 (slight enhancement); 2 (intermediate between 1 and 3); and 3 (enhancement similar to that of vessels). Enhancement scores for the endolymphatic sac, subarcuate artery, and geniculate ganglion were higher in 3D rIR than in 3D SPGR. Washout of enhancement in the endolymphatic sac appeared to be delayed compared with that in the subarcuate artery, suggesting that the enhancement in the endolymphatic sac may have been due in part to non-vascular tissue enhancement. Enhancement of the cochlear lymph space was not observed in any of the subjects in 3D rIR and 3D SPGR. The 3D rIR sequence may be more sensitive than the 3D SPGR sequence in visualizing the enhancement of small structures in the temporal bone; however, enhancement of the cochlear fluid space could not be visualized even with 3D rIR, triple-dose contrast, and dedicated coils at 1.5 T.

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury.

PubMed

Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

2014-08-15

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Effect of puberty on body composition.

PubMed

Loomba-Albrecht, Lindsey A; Styne, Dennis M

2009-02-01

Here we examine the effect of puberty on components of human body composition, including adiposity (total body fat, percentage body fat and fat distribution), lean body mass and bone mineral content and density. New methods and longitudinal studies have expended our knowledge of these remarkable changes. Human differences in adiposity, fat free mass and bone mass reflect differences in endocrine status (particularly with respect to estrogens, androgens, growth hormone and IGF-1), genetic factors, ethnicity and the environment. During puberty, males gain greater amounts of fat free mass and skeletal mass, whereas females acquire significantly more fat mass. Both genders reach peak bone accretion during the pubertal years, though males develop a greater skeletal mass. Body proportions and fat distribution change during the pubertal years as well, with males assuming a more android body shape and females assuming a more gynecoid shape. Pubertal body composition may predict adult body composition and affects both pubertal timing and future health. Sexual dimorphism exists to a small degree at birth, but striking differences develop during the pubertal years. The development of this dimorphism in body composition is largely regulated by endocrine factors, with critical roles played by growth hormone and gonadal steroids. It is important for clinicians and researchers to know the normal changes in order to address pathologic findings in disease states.

Osthole Promotes Bone Fracture Healing through Activation of BMP Signaling in Chondrocytes.

PubMed

Wang, Pinger; Ying, Jun; Luo, Cheng; Jin, Xing; Zhang, Shanxing; Xu, Taotao; Zhang, Lei; Mi, Meng; Chen, Di; Tong, Peijian; Jin, Hongting

2017-01-01

Osthole is a bioactive coumarin derivative and has been reported to be able to enhance bone formation and improve fracture healing. However, the molecular mechanism of Osthole in bone fracture healing has not been fully defined. In this study we determined if Osthole enhances bone fracture healing through activation of BMP2 signaling in mice. We performed unilateral open transverse tibial fracture procedure in 10-week-old C57BL/6 mice which were treated with or without Osthole. Our previous studies demonstrated that chondrocyte BMP signaling is required for bone fracture healing, in this study we also performed tibial fracture procedure in Cre-negative and Col2-Cre;Bmp2 flox/flox conditional knockout (KO) mice ( Bmp2 Col2Cre ) to determine if Osthole enhances fracture healing in a BMP2-dependent manner. Fracture callus tissues were collected and analyzed by X-ray, micro-CT (μCT), histology, histomorphometry, immunohistochemistry (IHC), biomechanical testing and quantitative gene expression analysis. In addition, mouse chondrogenic ATDC5 cells were cultured with or without Osthole and the expression levels of chondrogenic marker genes were examined. The results demonstrated that Osthole promotes bone fracture healing in wild-type (WT) or Cre - control mice. In contrast, Osthole failed to promote bone fracture healing in Bmp2 Col2Cre conditional KO mice. In the mice receiving Osthole treatment, expression of cartilage marker genes was significantly increased. We conclude that Osthole could promote bone strength and enhance fracture healing by activation of BMP2 signaling. Osthole may be used as an alternative approach in the orthopaedic clinic for the treatment of fracture healing.

Osthole Promotes Bone Fracture Healing through Activation of BMP Signaling in Chondrocytes

PubMed Central

Wang, Pinger; Ying, Jun; Luo, Cheng; Jin, Xing; Zhang, Shanxing; Xu, Taotao; Zhang, Lei; Mi, Meng; Chen, Di; Tong, Peijian; Jin, Hongting

2017-01-01

Osthole is a bioactive coumarin derivative and has been reported to be able to enhance bone formation and improve fracture healing. However, the molecular mechanism of Osthole in bone fracture healing has not been fully defined. In this study we determined if Osthole enhances bone fracture healing through activation of BMP2 signaling in mice. We performed unilateral open transverse tibial fracture procedure in 10-week-old C57BL/6 mice which were treated with or without Osthole. Our previous studies demonstrated that chondrocyte BMP signaling is required for bone fracture healing, in this study we also performed tibial fracture procedure in Cre-negative and Col2-Cre;Bmp2flox/flox conditional knockout (KO) mice (Bmp2Col2Cre) to determine if Osthole enhances fracture healing in a BMP2-dependent manner. Fracture callus tissues were collected and analyzed by X-ray, micro-CT (μCT), histology, histomorphometry, immunohistochemistry (IHC), biomechanical testing and quantitative gene expression analysis. In addition, mouse chondrogenic ATDC5 cells were cultured with or without Osthole and the expression levels of chondrogenic marker genes were examined. The results demonstrated that Osthole promotes bone fracture healing in wild-type (WT) or Cre- control mice. In contrast, Osthole failed to promote bone fracture healing in Bmp2Col2Creconditional KO mice. In the mice receiving Osthole treatment, expression of cartilage marker genes was significantly increased. We conclude that Osthole could promote bone strength and enhance fracture healing by activation of BMP2 signaling. Osthole may be used as an alternative approach in the orthopaedic clinic for the treatment of fracture healing. PMID:28924381

Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic Implants in an Ectopic Model

PubMed Central

Klünter, Tim; Schulz, Peter; Deisinger, Ulrike; Diez, Claudius; Waiss, Waltraud; Kirschneck, Christian; Reichert, Torsten E.; Detsch, Rainer

2017-01-01

Background: The aim of the present study was to evaluate the degradation pattern of highly porous bioceramics as well as the bone formation in presence of bone morphogenetic protein 7 (BMP-7) in an ectopic site. Methods: Novel calcium phosphate ceramic cylinders sintered at 1,300°C with a total porosity of 92–94 vol%, 45 pores per inch, and sized 15 mm (Ø) × 5 mm were grafted on the musculus latissimus dorsi bilaterally in 10 Göttingen minipigs: group I (n = 5): hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus BCP. A test side was supplied in situ with 250 μg BMP-7. Fluorochrome bone labeling and computed tomography were performed in vivo. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome staining. Results: Bone formation was enhanced in the presence of BMP-7 in all ceramics (P = 0.001). Small spots of newly formed bone were observed in all implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP ceramics were almost completely degraded independently of the effect of BMP-7 after 14 weeks (P = 0.76), osteoclasts were not observed. Conclusions: BMP-7 enhanced bone formation and degradation of HA and BCP ceramics via osteoclast resorption. TCP degraded via dissolution. All ceramics were osteoinductive. Novel degradable HA and BCP ceramics in the presence of BMP-7 are promising bone substitutes in the growing individual. PMID:28740783

Enhancement of bone formation in hydroxyapatite implants by rhBMP-2 coating.

PubMed

Schnettler, Reinhard; Knöss, Peter D; Heiss, Christian; Stahl, Jens-Peter; Meyer, Christof; Kilian, Olaf; Wenisch, Sabine; Alt, Volker

2009-07-01

The combination of hydroxyapatite (HA) implants serving as osteoconductive scaffold with growth factors is an interesting approach for the improvement of bone defect healing. The purpose of this study was to test whether recombinant human bone morphogenetic protein-2 (rhBMP-2) coating of solid HA-implants improves bone formation in a cortical bone defect. Cylindrical trephine mill defects (diameter: 9.8 mm, depth: 10 mm) were created into the cortical tibia shaft of minipigs and subsequently filled either by plain HA cylinders (Endobon) or by rhBMP-2-coated HA cylinders. Fluorochrome labeling for the evaluation of time-dependent bone formation was done on days 8, 9, and 10 postsurgery with tetracyclin-100, at days 25 and 30 with alizarin-komplexon, and finally on days 32, 37, 73, and 79 with calcein green. Twelve weeks after implantation, the tibiae were harvested and were prepared for standard histological staining, fluorochrome analysis, and histomorphometry. Coating of HA implants with rhBMP-2 led to significant enhanced new bone formation of 84.7% (+/-4.6%) of the implant area with almost complete bony incorporation compared with only 27.7% (+/-8.5%) in the uncoated HA implants (p = 0.028). In both types of implants, osteoconduction of HA led to bone ingrowth of the surrounding host bone into the implants. However, only rhBMP-2-coated implants showed multitopic de novo bone formation reflecting the osteoinductive properties of rhBMP-2 in all areas of the HA implant. This study showed that the coating of HA ceramic implants with rhBMP-2 can significantly enhance new bone formation attributable to its osteoinductive effects. (c) 2008 Wiley Periodicals, Inc.

Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation.

PubMed

Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

2016-01-01

Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo.

Deficiency of bone marrow beta3-integrin enhances non-functional neovascularization.

PubMed

Watson, Alan R; Pitchford, Simon C; Reynolds, Louise E; Direkze, Natalie; Brittan, Mairi; Alison, Malcolm R; Rankin, Sara; Wright, Nicholas A; Hodivala-Dilke, Kairbaan M

2010-03-01

beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our studies demonstrate a role for BM beta3-integrin in VEGF-induced mobilization of bone marrow-derived cells to the peripheral circulation and for the functionality of those vessels in which BM-derived cells become incorporated.

Shaping skeletal growth by modular regulatory elements in the Bmp5 gene.

PubMed

Guenther, Catherine; Pantalena-Filho, Luiz; Kingsley, David M

2008-12-01

Cartilage and bone are formed into a remarkable range of shapes and sizes that underlie many anatomical adaptations to different lifestyles in vertebrates. Although the morphological blueprints for individual cartilage and bony structures must somehow be encoded in the genome, we currently know little about the detailed genomic mechanisms that direct precise growth patterns for particular bones. We have carried out large-scale enhancer surveys to identify the regulatory architecture controlling developmental expression of the mouse Bmp5 gene, which encodes a secreted signaling molecule required for normal morphology of specific skeletal features. Although Bmp5 is expressed in many skeletal precursors, different enhancers control expression in individual bones. Remarkably, we show here that different enhancers also exist for highly restricted spatial subdomains along the surface of individual skeletal structures, including ribs and nasal cartilages. Transgenic, null, and regulatory mutations confirm that these anatomy-specific sequences are sufficient to trigger local changes in skeletal morphology and are required for establishing normal growth rates on separate bone surfaces. Our findings suggest that individual bones are composite structures whose detailed growth patterns are built from many smaller lineage and gene expression domains. Individual enhancers in BMP genes provide a genomic mechanism for controlling precise growth domains in particular cartilages and bones, making it possible to separately regulate skeletal anatomy at highly specific locations in the body.

Silk coating on a bioactive ceramic scaffold for bone regeneration: effective enhancement of mechanical and in vitro osteogenic properties towards load-bearing applications.

PubMed

Li, Jiao Jiao; Roohani-Esfahani, Seyed-Iman; Kim, Kyungsook; Kaplan, David L; Zreiqat, Hala

2017-06-01

Bioactive ceramic scaffolds represent competitive choices for clinical bone reconstruction, but their widespread use is restricted by inherent brittleness and weak mechanical performance under load. This study reports the development of strong and tough bioactive scaffolds suitable for use in load-bearing bone reconstruction. A strong and bioactive ceramic scaffold (strontium-hardystonite-gahnite) is combined with single and multiple coating layers of silk fibroin to enhance its toughness, producing composite scaffolds which match the mechanical properties of cancellous bone and show enhanced capacity to promote in vitro osteogenesis. Also reported for the first time is a comparison of the coating effects obtained when a polymeric material is coated on ceramic scaffolds with differing microstructures, namely the strontium-hardystonite-gahnite scaffold with high-density struts as opposed to a conventional ceramic scaffold, such as biphasic calcium phosphate, with low-density struts. The results show that silk coating on a unique ceramic scaffold can lead to simple and effective enhancement of its mechanical and biological properties to suit a wider range of applications in clinical bone reconstruction, and also establish the influence of ceramic microstructure on the effectiveness of silk coating as a method of reinforcement when applied to different types of ceramic bone graft substitutes. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume.

PubMed

Wegman, F; Poldervaart, M T; van der Helm, Y J; Oner, F C; Dhert, W J; Alblas, J

2015-07-27

Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.

Phelligridin D-loaded oral nanotube titanium implant enhances osseointegration and prevents osteolysis in rat mandible.

PubMed

Kim, Ji-Eun; Takanche, Jyoti Shrestha; Kim, Jeong-Seok; Lee, Min-Ho; Jeon, Jae-Gyu; Park, Il-Song; Yi, Ho-Keun

2018-04-12

Poor bone quality and osteolysis are the major causes of implant failure in dentistry. Here, this study tested the effect of phelligridin D-loaded nanotubes titanium (Ti) for bone formation around the dental implants. The purpose of this study was to enhance osseointegration of phelligridin D-loaded implant into the bone for bone formation and prevention of osteolysis. Cell viability, crystal violet staining, Western blot, alizarin red S staining, alkaline phosphatase activity, tartrate-resistant acid phosphatase staining, micro-computed tromography (μ-CT), hematoxylin and eosin (H&E) and immunohistochemical staining were used in vitro and in vivo to test the biocompatibility of phelligridin D. Phelligridin D enhanced osteoblast differentiation and mineralization by increasing bone morphogenic protein-2/7 (BMP-2/7), Osterix, Runx-2, osteoprotegerin (OPG), alkaline phosphatase and inhibited osteoclast differentiation by decreasing receptor activator of nuclear factor kappa-B ligand (RANKL) in MC-3T3 E1 cells. Further, phelligridin D promoted bone regeneration around nanotube Ti implant surface by increasing the levels of BMP-2/7 and OPG in a rat model. Phelligridin D also inhibited osteolysis by suppressing the expression of RANKL. These findings strongly suggest that phelligridin D is a new compound representing a potential therapeutic candidate for implant failure caused by osteolysis and poor bone quality of teeth.

Jet Launching in Resistive GR-MHD Black Hole–Accretion Disk Systems

NASA Astrophysics Data System (ADS)

Qian, Qian; Fendt, Christian; Vourellis, Christos

2018-05-01

We investigate the launching mechanism of relativistic jets from black hole sources, in particular the strong winds from the surrounding accretion disk. Numerical investigations of the disk wind launching—the simulation of the accretion–ejection transition—have so far almost only been done for nonrelativistic systems. From these simulations we know that resistivity, or magnetic diffusivity, plays an important role for the launching process. Here we extend this treatment to general relativistic magnetohydrodynamics (GR-MHD), applying the resistive GR-MHD code rHARM. Our model setup considers a thin accretion disk threaded by a large-scale open magnetic field. We run a series of simulations with different Kerr parameter, field strength, and diffusivity level. Indeed, we find strong disk winds with, however, mildly relativistic speed, the latter most probably due to our limited computational domain. Further, we find that magnetic diffusivity lowers the efficiency of accretion and ejection, as it weakens the efficiency of the magnetic lever arm of the disk wind. As a major driving force of the disk wind we disentangle the toroidal magnetic field pressure gradient; however, magnetocentrifugal driving may also contribute. Black hole rotation in our simulations suppresses the accretion rate owing to an enhanced toroidal magnetic field pressure that seems to be induced by frame dragging. Comparing the energy fluxes from the Blandford–Znajek-driven central spine and the surrounding disk wind, we find that the total electromagnetic energy flux is dominated by the total matter energy flux of the disk wind (by a factor of 20). The kinetic energy flux of the matter outflow is comparatively small and comparable to the Blandford–Znajek electromagnetic energy flux.

The Infrared Medium-deep Survey. IV. The Low Eddington Ratio of A Faint Quasar at z ∼ 6: Not Every Supermassive Black Hole is Growing Fast in the Early Universe

NASA Astrophysics Data System (ADS)

Kim, Yongjung; Im, Myungshin; Jeon, Yiseul; Kim, Minjin; Hyun, Minhee; Kim, Dohyeong; Kim, Jae-Woo; Taak, Yoon Chan; Yoon, Yongmin; Choi, Changsu; Hong, Jueun; Jun, Hyunsung David; Karouzos, Marios; Kim, Duho; Kim, Ji Hoon; Lee, Seong-Kook; Pak, Soojong; Park, Won-Kee

2018-03-01

To date, most of the luminous quasars known at z ∼ 6 have been found to be in maximal accretion with the Eddington ratios, {λ }Edd}∼ 1, suggesting enhanced nuclear activities in the early universe. However, this may not be the whole picture of supermassive black hole (SMBH) growth, since previous studies have not reached faint quasars that are more likely to harbor SMBHs with low {λ }Edd}. To gain a better understanding of the accretion activities in quasars in the early universe, we obtained a deep near-infrared (NIR) spectrum of a quasar, IMS J220417.92+011144.8 (hereafter IMS J2204+0112), one of the faintest quasars that has been identified at z ∼ 6. From the redshifted C IV λ1549 emission line in the NIR spectrum, we find that IMS J2204+0112 harbors a SMBH with a solar mass of about a billion and {λ }Edd}∼ 0.1, but with a large uncertainty in both quantities (0.41 dex). IMS J2204+0112 has one of the lowest Eddington ratios among quasars at z ∼ 6, but a common value among quasars at z ∼ 2. Its low {λ }Edd} can be explained with two scenarios; the SMBH growth from a stellar-mass black hole through short-duration super-Eddington accretion events or from a massive black hole seed (∼ {10}5 {M}ȯ ) with Eddington-limited accretion. NIR spectra of more faint quasars are needed to better understand the accretion activities of SMBHs at z ∼ 6.

Evidence for hot clumpy accretion flow in the transitional millisecond pulsar PSR J1023+0038

NASA Astrophysics Data System (ADS)

Shahbaz, T.; Dallilar, Y.; Garner, A.; Eikenberry, S.; Veledina, A.; Gandhi, P.

2018-06-01

We present simultaneous optical and near-infrared (IR) photometry of the millisecond pulsar PSR J1023+0038 during its low-mass X-ray binary phase. The r΄- and Ks-band light curves show rectangular, flat-bottomed dips, similar to the X-ray mode-switching (active-passive state transitions) behaviour observed previously. The cross-correlation function (CCF) of the optical and near-IR data reveals a strong, broad negative anticorrelation at negative lags, a broad positive correlation at positive lags, with a strong, positive narrow correlation superimposed. The shape of the CCF resembles the CCF of black hole X-ray binaries but the time-scales are different. The features can be explained by reprocessing and a hot accretion flow close to the neutron star's magnetospheric radius. The optical emission is dominated by the reprocessed component, whereas the near-IR emission contains the emission from plasmoids in the hot accretion flow and a reprocessed component. The rapid active-passive state transition occurs when the hot accretion flow material is channelled on to the neutron star and is expelled from its magnetosphere. During the transition the optical reprocessing component decreases resulting in the removal of a blue spectral component. The accretion of clumpy material through the magnetic barrier of the neutron star produces the observed near-IR/optical CCF and variability. The dip at negative lags corresponds to the suppression of the near-IR synchrotron component in the hot flow, whereas the broad positive correlation at positive lags is driven by the increased synchrotron emission of the outflowing plasmoids. The narrow peak in the CCF is due to the delayed reprocessed component, enhanced by the increased X-ray emission.

Oxytocin and bone

PubMed Central

Sun, Li; Zaidi, Mone; Zallone, Alberta

2014-01-01

One of the most meaningful results recently achieved in bone research has been to reveal that the pituitary hormones have profound effect on bone, so that the pituitary-bone axis has become one of the major topics in skeletal physiology. Here, we discuss the relevant evidence about the posterior pituitary hormone oxytocin (OT), previously thought to exclusively regulate parturition and breastfeeding, which has recently been established to directly regulate bone mass. Both osteoblasts and osteoclasts express OT receptors (OTR), whose stimulation enhances bone mass. Consistent with this, mice deficient in OT or OTR display profoundly impaired bone formation. In contrast, bone resorption remains unaffected in OT deficiency because, even while OT stimulates the genesis of osteoclasts, it inhibits their resorptive function. Furthermore, in addition to its origin from the pituitary, OT is also produced by bone marrow osteoblasts acting as paracrine-autocrine regulator of bone formation modulated by estrogens. In turn, the power of estrogen to increase bone mass is OTR-dependent. Therefore, OTR−/− mice injected with 17β-estradiol do not show any effects on bone formation parameters, while the same treatment increases bone mass in wild-type mice. These findings together provide evidence for an anabolic action of OT in regulating bone mass and suggest that bone marrow OT may enhance the bone-forming action of estrogen through an autocrine circuit. This established new physiological role for OT in the maintenance of skeletal integrity further suggests the potential use of this hormone for the treatment of osteoporosis. PMID:25209411

Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment

DTIC Science & Technology

2013-10-01

Employment opportunities received based upon experience/ training supported by this award Partly based upon her research during the completion of...School, Coventry CV4 7AL, United Kingdom References 1. Stevenson S. Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin

Analysis of imaging characteristics of primary malignant bone tumors in children

PubMed Central

Sun, Yingwei; Liu, Xueyong; Pan, Shinong; Deng, Chunbo; Li, Xiaohan; Guo, Qiyong

2017-01-01

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a compression fracture of L1. MRI showed a soft-tissue mass with low T1 signal and high T2 signal and marked inhomogeneous enhancement. Overall, osteosarcoma was the most common primary malignant bone tumor, followed by Ewing sarcoma, chondrosarcoma and lymphoma. Osteoblastic or osteolytic bone destruction, an invasive periosteal reaction, soft-tissue masses, a tumor matrix and inhomogeneous enhancement were important imaging features of malignant bone tumors. PMID:29113210

Modulation of Stromal Cell-Derived Factor-1/CXC Chemokine Receptor 4 Axis Enhances rhBMP-2-Induced Ectopic Bone Formation

PubMed Central

Wise, Joel K.; Sumner, Dale Rick

2012-01-01

Enhancement of in vivo mobilization and homing of endogenous mesenchymal stem cells (MSCs) to an injury site is an innovative strategy for improvement of bone tissue engineering and repair. The present study was designed to determine whether mobilization by AMD3100 and/or local homing by delivery of stromal cell-derived factor-1 (SDF-1) enhances recombinant human bone morphogenetic protein-2 (rhBMP-2) induced ectopic bone formation in an established rat model. Rats received an injection of either saline or AMD3100 treatment 1 h before harvesting of bone marrow for in vitro colony-forming unit-fibroblasts (CFU-F) culture or the in vivo subcutaneous implantation of absorbable collagen sponges (ACSs) loaded with saline, recombinant human bone morphogenetic protein-2 (rhBMP-2), SDF-1, or the combination of SDF-1 and rhBMP-2. AMD3100 treatment resulted in a significant decrease in CFU-F number, compared with saline, which confirmed that a single systemic AMD3100 treatment rapidly mobilized MSCs from the bone marrow. At 28 and 56 days, bone formation in the explanted ACS was assessed by microcomputed tomography (μCT) and histology. At 28 days, AMD3100 and/or SDF-1 had no statistically significant effect on bone volume (BV) or bone mineral content (BMC), but histology revealed more active bone formation with treatment of AMD3100, loading of SDF-1, or the combination of both AMD3100 and SDF-1, compared with saline-treated rhBMP-2 loaded ACS. At 56 days, the addition of AMD3100 treatment, loading of SDF-1, or the combination of both resulted in a statistically significant stimulatory effect on BV and BMC, compared with the saline-treated rhBMP-2 loaded ACS. Histology of the 56-day ACS were consistent with the μCT analysis, exhibiting more mature and mineralized bone formation with AMD3100 treatment, SDF-1 loading, or the combination of both, compared with the saline-treated rhBMP-2 loaded ACS. The present study is the first that provides evidence of the efficacy of AMD3100 and SDF-1 treatment to stimulate trafficking of MSCs to an ectopic implant site, in order to ultimately enhance rhBMP-2 induced long-term bone formation. PMID:22035136

Direct Lentiviral-Cyclooxygenase 2 Application to the Tendon-Bone Interface Promotes Osteointegration and Enhances Return of the Pull-Out Tensile Strength of the Tendon Graft in a Rat Model of Biceps Tenodesis

PubMed Central

Wergedal, Jon E.; Stiffel, Virginia; Lau, Kin-Hing William

2014-01-01

This study sought to determine if direct application of the lentiviral (LV)-cyclooxygenase 2 (COX2) vector to the tendon-bone interface would promote osteointegration of the tendon graft in a rat model of biceps tenodesis. The LV-COX2 gene transfer strategy was chosen for investigation because a similar COX2 gene transfer strategy promoted bony bridging of the fracture gap during bone repair, which involves similar histologic transitions that occur in osteointegration. Briefly, a 1.14-mm diameter tunnel was drilled in the mid-groove of the humerus of adult Fischer 344 rats. The LV-COX2 or βgal control vector was applied directly into the bone tunnel and onto the end of the tendon graft, which was then pulled into the bone tunnel. A poly-L-lactide pin was press-fitted into the tunnel as interference fixation. Animals were sacrificed at 3, 5, or 8 weeks for histology analysis of osteointegration. The LV-COX2 gene transfer strategy enhanced neo-chondrogenesis at the tendon-bone interface but with only marginal effect on de novo bone formation. The tendon-bone interface of the LV-COX2-treated tenodesis showed the well-defined tendon-to-fibrocartilage-to-bone histologic transitions that are indicative of osteointegration of the tendon graft. The LV-COX2 in vivo gene transfer strategy also significantly enhanced angiogenesis at the tendon-bone interface. To determine if the increased osteointegration was translated into an improved pull-out mechanical strength property, the pull-out tensile strength of the LV-COX2-treated tendon grafts was determined with a pull-out mechanical testing assay. The LV-COX2 strategy yielded a significant improvement in the return of the pull-out strength of the tendon graft after 8 weeks. In conclusion, the COX2-based in vivo gene transfer strategy enhanced angiogenesis, osteointegration and improved return of the pull-out strength of the tendon graft. Thus, this strategy has great potential to be developed into an effective therapy to promote tendon-to-bone healing after tenodesis or related surgeries. PMID:24848992

Novel 3D Tissue Engineered Bone Model, Biomimetic Nanomaterials, and Cold Atmospheric Plasma Technique for Biomedical Applications

NASA Astrophysics Data System (ADS)

Wang, Mian

This thesis research is consist of four chapters, including biomimetic three-dimensional tissue engineered nanostructured bone model for breast cancer bone metastasis study (Chapter one), cold atmospheric plasma for selectively ablating metastatic breast cancer (Chapter two), design of biomimetic and bioactive cold plasma modified nanostructured scaffolds for enhanced osteogenic differentiation of bone marrow derived mesenchymal stem cells (Chapter three), and enhanced osteoblast and mesenchymal stem cell functions on titanium with hydrothermally treated nanocrystalline hydroxyapatite/magnetically treated carbon nanotubes for orthopedic applications (Chapter four). All the thesis research is focused on nanomaterials and the use of cold plasma technique for various biomedical applications.

Bone Marrow Aspirate Concentrate-Enhanced Marrow Stimulation of Chondral Defects

PubMed Central

Eichler, Hermann; Orth, Patrick

2017-01-01

Mesenchymal stem cells (MSCs) from bone marrow play a critical role in osteochondral repair. A bone marrow clot forms within the cartilage defect either as a result of marrow stimulation or during the course of the spontaneous repair of osteochondral defects. Mobilized pluripotent MSCs from the subchondral bone migrate into the defect filled with the clot, differentiate into chondrocytes and osteoblasts, and form a repair tissue over time. The additional application of a bone marrow aspirate (BMA) to the procedure of marrow stimulation is thought to enhance cartilage repair as it may provide both an additional cell population capable of chondrogenesis and a source of growth factors stimulating cartilage repair. Moreover, the BMA clot provides a three-dimensional environment, possibly further supporting chondrogenesis and protecting the subchondral bone from structural alterations. The purpose of this review is to bridge the gap in our understanding between the basic science knowledge on MSCs and BMA and the clinical and technical aspects of marrow stimulation-based cartilage repair by examining available data on the role and mechanisms of MSCs and BMA in osteochondral repair. Implications of findings from both translational and clinical studies using BMA concentrate-enhanced marrow stimulation are discussed. PMID:28607559

The role of versican G3 domain in regulating breast cancer cell motility including effects on osteoblast cell growth and differentiation in vitro – evaluation towards understanding breast cancer cell bone metastasis

PubMed Central

2012-01-01

Background Versican is detected in the interstitial tissues at the invasive margins of breast carcinoma, is predictive of relapse, and negatively impacts overall survival rates. The versican G3 domain is important in breast cancer cell growth, migration and bone metastasis. However, mechanistic studies evaluating versican G3 enhanced breast cancer bone metastasis are limited. Methods A versican G3 construct was exogenously expressed in the 66c14 and the MC3T3-E1 cell line. Cells were observed through light microscopy and viability analyzed by Coulter Counter or determined with colorimetric proliferation assays. The Annexin V-FITC apoptosis detection kit was used to detect apoptotic activity. Modified Chemotactic Boyden chamber migration invasion assays were applied to observe tumor migration and invasion to bone stromal cells and MC3T3-E1 cells. Alkaline phosphatase (ALP) staining and ALP ELISA assays were performed to observe ALP activity in MC3T3-E1 cells. Results In the four mouse breast cancer cell lines 67NR, 66c14, 4T07, and 4T1, 4T1 cells expressed higher levels of versican, and showed higher migration and invasion ability to MC3T3-E1 cells and primary bone stromal cells. 4T1 conditioned medium (CM) inhibited MC3T3-E1 cell growth, and even lead to apoptosis. Only 4T1 CM prevented MC3T3-E1 cell differentiation, noted by inhibition of alkaline phosphatase (ALP) activity. We exogenously expressed a versican G3 construct in a cell line that expresses low versican levels (66c14), and observed that the G3-expressing 66c14 cells showed enhanced cell migration and invasion to bone stromal and MC3T3-E1 cells. This observation was prevented by selective EGFR inhibitor AG1478, selective MEK inhibitor PD 98059, and selective AKT inhibitor Triciribine, but not by selective JNK inhibitor SP 600125. Versican G3 enhanced breast cancer cell invasion to bone stromal cells or osteoblast cells appears to occur through enhancing EGFR/ERK or AKT signaling. G3 expressing MC3T3-E1 cells showed inhibited cell growth and cell differentiation when cultured with TGF-β1 (1 ng/ml), and expressed enhanced cell apoptosis when cultured with TNF-α (2 ng/ml). Enhanced EGFR/JNK signaling appears to be responsible for G3 enhanced osteoblast apoptosis and inhibited osteoblast differentiation. Whereas repressed expression of GSK-3β (S9P) contributes to G3 inhibited osteoblast growth. Versican G3 functionality was dependent on its EGF-like motifs. Without the structure of EGF-like repeats, the G3 domain would not confer enhancement of tumor cell migration and invasion to bone with concordant inhibition of osteoblast differentiation and promotion of osteoblast apoptosis. Conclusions Versican enhances breast cancer bone metastasis not only through enhancing tumor cell mobility, invasion, and survival in bone tissues, but also by inhibiting pre-osteoblast cell growth, differentiation, which supply favorable microenvironments for tumor metastasis. PMID:22862967

ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae.

PubMed

Elefteriou, Florent; Benson, M Douglas; Sowa, Hideaki; Starbuck, Michael; Liu, Xiuyun; Ron, David; Parada, Luis F; Karsenty, Gerard

2006-12-01

The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1(ob)(-/-) mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1(ob)(-/-) mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1(ob)(-/-) mice without affecting other organ weight, while a high-protein diet overcame Atf4(-/-) and Rsk2(-/-) mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development.

microRNAs as regulators of adipogenic differentiation of mesenchymal stem cells.

PubMed

Hamam, Dana; Ali, Dalia; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

2015-02-15

microRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel approaches for enhancing osteoblastic bone formation through inhibition of bone marrow fat formation. A number of recent studies have reported several miRNAs that enhance or inhibit adipogenic differentiation of MSCs and with potential use in microRNA-based therapy to regulate adipogenesis in the context of treating bone diseases and metabolic disorders. The current review focuses on miRNAs and their role in regulating adipogenic differentiation of MSCs.

Role of platelet-rich plasma in combination with alloplastic bone substitute in regeneration of osseous defects

PubMed Central

Singh, Indrajeet; Gupta, Hemant; Pradhan, R; Sinha, VP; Gupta, Sumit

2012-01-01

Introduction Bone grafts are frequently used for the treatment of bone defects, but can cause postoperative complications, and sometimes a sufficient quantity of bone is not available. Hence, synthetic biomaterials have been used as an alternative to autogenous bone grafts. Recent clinical reports suggest that application of autologous blood plasma enriched with platelets can enhance the formation of new bone. There are very few in vitro or in vivo studies published on the efficiency of platelet-rich plasma (PRP). The objective of this study was to evaluate the alloplastic bone substitute for its osteogenic potential with or without PRP. Materials and Methods Twenty-three patients with periapical bony defects were selected for this study. Clinical parameters such as pain visual analog scale (VAS), swelling, infection, graft migration, rejection, radiographical interpretations at regular interval and scintigraphic evaluation were done to evaluate osteogenic potential of alloplastic bone substitute with or without PRP. Results The highest acceleration in bone formation was observed in groups where alloplastic bone substitute was used with PRP. There were no statistically significant differences between the two groups regarding other outcome variables throughout the postoperative period. Conclusion Addition of PRP significantly accelerates vascularization of the graft, improves soft tissue healing, reduces postoperative morbidity and enhances bone regeneration. PMID:25756013

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

PubMed Central

Gao, Liang; Orth, Patrick; Müller-Brandt, Kathrin; Goebel, Lars K. H.; Cucchiarini, Magali; Madry, Henning

2017-01-01

Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques. PMID:28345610

Rapamycin and the transcription factor C/EBPbeta as a switch in osteoclast differentiation: implications for lytic bone diseases.

PubMed

Smink, Jeske J; Leutz, Achim

2010-03-01

Lytic bone diseases and in particular osteoporosis are common age-related diseases characterized by enhanced bone fragility due to loss of bone density. Increasingly, osteoporosis poses a major global health-care problem due to the growth of the elderly population. Recently, it was found that the gene regulatory transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) is involved in bone metabolism. C/EBPbeta occurs as different protein isoforms of variable amino terminal length, and regulation of the C/EBPbeta isoform ratio balance was found to represent an important factor in osteoclast differentiation and bone homeostasis. Interestingly, adjustment of the C/EBPbeta isoform ratio by the process of translational control is downstream of the mammalian target of rapamycin kinase (mTOR), a sensor of the nutritional status and a target of immunosuppressive and anticancer drugs. The findings imply that modulating the process of translational control of C/EBPbeta isoform expression could represent a novel therapeutic approach in osteolytic bone diseases, including cancer and infection-induced bone loss.

Coating of VEGF-releasing scaffolds with bioactive glass for angiogenesis and bone regeneration.

PubMed

Leach, J Kent; Kaigler, Darnell; Wang, Zhuo; Krebsbach, Paul H; Mooney, David J

2006-06-01

Bioactive glasses are potentially useful as bone defect fillers, and vascular endothelial growth factor (VEGF) has demonstrated benefit in bone regeneration as well. We hypothesized that the specific combination of prolonged localized VEGF presentation from a matrix coated with a bioactive glass may enhance bone regeneration. To test this hypothesis, the capacity of VEGF-releasing polymeric scaffolds with a bioactive glass coating was examined in vitro and in vivo using a rat critical-sized defect model. In the presence of a bioactive glass coating, we did not detect pronounced differences in the differentiation of human mesenchymal stem cells in vitro. However, we observed significantly enhanced mitogenic stimulation of endothelial cells in the presence of the bioactive glass coating, with an additive effect with VEGF release. This trend was maintained in vivo, where coated VEGF-releasing scaffolds demonstrated significant improvements in blood vessel density at 2 weeks versus coated control scaffolds. At 12 weeks, bone mineral density was significantly increased in coated VEGF-releasing scaffolds versus coated controls, while only a slight increase in bone volume fraction was observed. The results of this study suggest that a bioactive glass coating on a polymeric substrate participates in bone healing through indirect processes which enhance angiogenesis and bone maturation and not directly on osteoprogenitor differentiation and bone formation. The mass of bioactive glass used in this study provides a comparable and potentially additive, response to localized VEGF delivery over early time points. These studies demonstrate a materials approach to achieve an angiogenic response formerly limited to the delivery of inductive growth factors.

Anabolic agents and bone quality.

PubMed

Sibai, Tarek; Morgan, Elise F; Einhorn, Thomas A

2011-08-01

The definition of bone quality is evolving particularly from the perspective of anabolic agents that can enhance not only bone mineral density but also bone microarchitecture, composition, morphology, amount of microdamage, and remodeling dynamics. This review summarizes the molecular pathways and physiologic effects of current and potential anabolic drugs. From a MEDLINE search (1996-2010), articles were identified by the search terms "bone quality" (1851 articles), "anabolic agent" (5044 articles), "PTH or parathyroid hormone" (32,229 articles), "strontium" or "strontium ranelate" (283 articles), "prostaglandin" (77,539 articles), and "statin" or "statins" (14,233 articles). The search strategy included combining each with the phrase "bone quality." Another more limited search aimed at finding more novel potential agents. Parathyroid hormone is the only US Food and Drug Administration-approved bone anabolic agent in the United States and has been the most extensively studied in in vitro animal and human trials. Strontium ranelate is approved in Europe but has not undergone Food and Drug Administration trials in the United States. All the studies on prostaglandin agonists have used in vivo animal models and there are no human trials examining prostaglandin agonist effects. The advantages of statins include the long-established advantages and safety profile, but they are limited by their bioavailability in bone. Other potential pathways include proline-rich tyrosine kinase 2 (PYK2) and sclerostin (SOST) inhibition, among others. The ongoing research to enhance the anabolic potential of current agents, identify new agents, and develop better delivery systems will greatly enhance the management of bone quality-related injuries and diseases in the future.

Wedelolactone enhances osteoblastogenesis by regulating Wnt/β-catenin signaling pathway but suppresses osteoclastogenesis by NF-κB/c-fos/NFATc1 pathway.

PubMed

Liu, Yan-Qiu; Hong, Zhi-Lai; Zhan, Li-Bin; Chu, Hui-Ying; Zhang, Xiao-Zhe; Li, Guo-Hui

2016-08-25

Bone homeostasis is maintained by formation and destruction of bone, which are two processes tightly coupled and controlled. Targeting both stimulation on bone formation and suppression on bone resorption becomes a promising strategy for treating osteoporosis. In this study, we examined the effect of wedelolactone, a natural product from Ecliptae herba, on osteoblastogenesis as well as osteoclastogenesis. In mouse bone marrow mesenchymal stem cells (BMSC), wedelolactone stimulated osteoblast differentiation and bone mineralization. At the molecular level, wedelolactone directly inhibited GSK3β activity and enhanced the phosphorylation of GSK3β, thereafter stimulated the nuclear translocation of β-catenin and runx2. The expression of osteoblastogenesis-related marker gene including osteorix, osteocalcin and runx2 increased. At the same concentration range, wedelolactone inhibited RANKL-induced preosteoclastic RAW264.7 actin-ring formation and bone resorption pits. Further, wedelolactone blocked NF-kB/p65 phosphorylation and abrogated the NFATc1 nuclear translocation. As a result, osteoclastogenesis-related marker gene expression decreased, including c-src, c-fos, and cathepsin K. In ovariectomized mice, administration of wedelolactone prevented ovariectomy-induced bone loss by enhancing osteoblast activity and inhibiting osteoclast activity. Together, these data demonstrated that wedelolactone facilitated osteoblastogenesis through Wnt/GSK3β/β-catenin signaling pathway and suppressed RANKL-induced osteoclastogenesis through NF-κB/c-fos/NFATc1 pathway. These results suggested that wedelolacone could be a novel dual functional therapeutic agent for osteoporosis.

Continuous delivery of rhBMP2 and rhVEGF165 at a certain ratio enhances bone formation in mandibular defects over the delivery of rhBMP2 alone--An experimental study in rats.

PubMed

Lohse, N; Moser, N; Backhaus, S; Annen, T; Epple, M; Schliephake, H

2015-12-28

The aim of the present study was to test the hypothesis that different amounts of vascular endothelial growth factor and bone morphogenic protein differentially affect bone formation when applied for repair of non-healing defects in the rat mandible. Porous composite PDLLA/CaCO3 carriers were fabricated as slow release carriers and loaded with rhBMP2 and rhVEGF165 in 10 different dosage combinations using gas foaming with supercritical carbon dioxide. They were implanted in non-healing defects of the mandibles of 132 adult Wistar rats with additional lateral augmentation. Bone formation was assessed both radiographically (bone volume) and by histomorphometry (bone density). The use of carriers with a ratio of delivery of VEGF/BMP between 0.7 and 1.2 was significantly related to the occurrence of significant increases in radiographic bone volume and/or histologic bone density compared to the use of carriers with a ratio of delivery of ≤ 0.5 when all intervals and all outcome parameters were considered. Moreover, simultaneous delivery at this ratio helped to "save" rhBMP2 as both bone volume and bone density after 13 weeks were reached/surpassed using half the dosage required for rhBMP2 alone. It is concluded, that the combined delivery of rhVEGF165 and rhBMP2 for repair of critical size mandibular defects can significantly enhance volume and density of bone formation over delivery of rhBMP2 alone. It appears from the present results that continuous simultaneous delivery of rhVEGF165 and rhBMP2 at a ratio of approximately 1 is favourable for the enhancement of bone formation. Copyright © 2015. Published by Elsevier B.V.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

PubMed

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

A peptide that blocks the interaction of NF-κB p65 subunit with Smad4 enhances BMP2-induced osteogenesis.

PubMed

Urata, Mariko; Kokabu, Shoichiro; Matsubara, Takuma; Sugiyama, Goro; Nakatomi, Chihiro; Takeuchi, Hiroshi; Hirata-Tsuchiya, Shizu; Aoki, Kazuhiro; Tamura, Yukihiko; Moriyama, Yasuko; Ayukawa, Yasunori; Matsuda, Miho; Zhang, Min; Koyano, Kiyoshi; Kitamura, Chiaki; Jimi, Eijiro

2018-09-01

Bone morphogenetic protein (BMP) potentiates bone formation through the Smad signaling pathway in vitro and in vivo. The transcription factor nuclear factor κB (NF-κB) suppresses BMP-induced osteoblast differentiation. Recently, we identified that the transactivation (TA) 2 domain of p65, a main subunit of NF-κB, interacts with the mad homology (MH) 1 domain of Smad4 to inhibit BMP signaling. Therefore, we further attempted to identify the interacting regions of these two molecules at the amino acid level. We identified a region that we term the Smad4-binding domain (SBD), an amino-terminal region of TA2 that associates with the MH1 domain of Smad4. Cell-permeable SBD peptide blocked the association of p65 with Smad4 and enhanced BMP2-induced osteoblast differentiation and mineralization without affecting the phosphorylation of Smad1/5 or the activation of NF-κB signaling. SBD peptide enhanced the binding of the BMP2-inudced phosphorylated Smad1/5 on the promoter region of inhibitor of DNA binding 1 (Id-1) compared with control peptide. Although SBD peptide did not affect BMP2-induced chondrogenesis during ectopic bone formation, the peptide enhanced BMP2-induced ectopic bone formation in subcortical bone. Thus, the SBD peptide is useful for enabling BMP2-induced bone regeneration without inhibiting NF-κB activity. © 2018 Wiley Periodicals, Inc.

Forskolin enhances in vivo bone formation by human mesenchymal stromal cells.

PubMed

Doorn, Joyce; Siddappa, Ramakrishnaiah; van Blitterswijk, Clemens A; de Boer, Jan

2012-03-01

Activation of the protein kinase A (PKA) pathway with dibutyryl cyclic adenosine monophosphate (db-cAMP) was recently shown to enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs) in vitro and bone formation in vivo. The major drawback of this compound is its inhibitory effect on proliferation of hMSCs. Therefore, we investigated whether fine-tuning of the dose and timing of PKA activation could enhance bone formation even further, with minimum effects on proliferation. To test this, we selected two different PKA activators (8-bromo-cAMP (8-br-cAMP) and forskolin) and compared their effects on proliferation and osteogenic differentiation with those of db-cAMP. We found that all three compounds induced alkaline phosphatase levels, bone-specific target genes, and secretion of insulin-like growth factor-1, although 8-br-cAMP induced adipogenic differentiation in long-term cultures and was thus considered unsuitable for further in vivo testing. All three compounds inhibited proliferation of hMSCs in a dose-dependent manner, with forskolin inhibiting proliferation most. The effect of forskolin on in vivo bone formation was tested by pretreating hMSCs before implantation, and we observed greater amounts of bone using forskolin than db-cAMP. Our data show forskolin to be a novel agent that can be used to increase bone formation and also suggests a role for PKA in the delicate balance between adipogenic and osteogenic differentiation.

Accretion rate of extraterrestrial matter: Iridium deposited over the last 70 million years

NASA Technical Reports Server (NTRS)

Kyte, Frank T.

1988-01-01

In order to quantify the accretion rate of extraterrestrial matter during the Cenozoic, Ir concentrations were measured in a continuous series of 450 samples across most of the length of piston core LL44-GPC3. LL44-GPC3 is a 25-meter-long, large-diameter piston core of abyssal clay from the central North Pacific. This core contains a nearly continuous record of sedimentation over the last 70 Ma, as this site migrated from a region near the Equator in the late Cretaceous to its present position north of Hawaii. The first-cut survey across the core is nearing completion, and all of the conclusions of the earlier study, in which was reported the concentrations of Ir, Co, and Sb across 9 meters of this core, remain unchanged. The only strongly enhanced Ir concentrations occur at the Cretaceous-Tertiary (K-T) boundary and outside the K-T boundary Ir correlates well with Co, a terrestrial element which is largely present in hydrogenous ferromanganese oxide precipitates from seawater. Concentrations of both elements appear to be inversely correlated with the sedimentation rate. Although the K-T Ir anomaly is unique in magnitude in this core, there are several small bumps in the Ir profile which may reflect smaller accretionary events. The most promising Ir enhancement was observed in a 30 cm section approximately 1 m below the K-T boundary. Preliminary data suggest deposition of an excess across this interval at a time estimate to be approximate 1 Ma before the K-T impact event, but there is insufficient evidence at present to prove that this reflects enhanced accretion of extraterrestrial matter. A detailed model is being prepared of the chemical record of sedimentation in this core using a combined database of 39 elements in approximately 450 samples across the Cenozoic. Preliminary working model indicates that the only sedimentary sources which contribute significantly to the Ir budget in this core are the hydrogenous precipitates and extraterrestrial particulates.

Dosimetric measurement of scattered radiation from dental implants in simulated head and neck radiotherapy.

PubMed

Wang, R; Pillai, K; Jones, P K

1998-01-01

The purpose of this study was to examine the dose enhancement at bone-implant interfaces from scattered radiation during simulated head and neck radiotherapy. Three cylindric implant systems with different compositions (pure titanium, titanium-aluminum-vanadium alloy, titanium coated with hydroxyapatite) and a high gold content transmandibular implant system (gold-copper-silver alloy) were studied. Extruded lithium fluoride single crystal chips were used as thermoluminescent material to measure radiation dose enhancement at 0, 1, and 2 mm from the bone-implant interface. The relative doses in buccal, lingual, mesial, and distal directions were also recorded and compared. The results indicated that the highest dose enhancement occurred at a distance of 0 mm from the bone-implant interface for all the implant systems studied. The transmandibular implants had higher scattered radiation than other groups at 0 mm and at 1 mm from the bone-implant interface. There was no significant difference of dose enhancement between buccal, lingual, mesial, and distal directions. Titanium implants coated with hydroxyapatite demonstrated the best results under the simulated irradiation.

Regulation of bone remodeling by vasopressin explains the bone loss in hyponatremia

PubMed Central

Tamma, Roberto; Sun, Li; Cuscito, Concetta; Lu, Ping; Corcelli, Michelangelo; Li, Jianhua; Colaianni, Graziana; Moonga, Surinder S.; Di Benedetto, Adriana; Grano, Maria; Colucci, Silvia; Yuen, Tony; New, Maria I.; Zallone, Alberta; Zaidi, Mone

2013-01-01

Although hyponatremia is known to be associated with osteoporosis and a high fracture risk, the mechanism through which bone loss ensues has remained unclear. As hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, we examined whether AVP can affect the skeleton directly as yet another component of the pituitary-bone axis. Here, we report that the two Avp receptors, Avpr1α and Avpr2, coupled to Erk activation, are expressed in osteoblasts and osteoclasts. AVP injected into wild-type mice enhanced and reduced, respectively, the formation of bone-resorbing osteoclasts and bone-forming osteoblasts. Conversely, the exposure of osteoblast precursors to Avpr1α or Avpr2 antagonists, namely SR49059 or ADAM, increased osteoblastogenesis, as did the genetic deletion of Avpr1α. In contrast, osteoclast formation and bone resorption were both reduced in Avpr1α−/− cultures. This process increased bone formation and reduced resorption resulted in a profound enhancement of bone mass in Avpr1α−/− mice and in wild-type mice injected with SR49059. Collectively, the data not only establish a primary role for Avp signaling in bone mass regulation, but also call for further studies on the skeletal actions of Avpr inhibitors used commonly in hyponatremic patients. PMID:24167258

Global deletion of tetraspanin CD82 attenuates bone growth and enhances bone marrow adipogenesis.

PubMed

Bergsma, Alexis; Ganguly, Sourik S; Dick, Daniel; Williams, Bart O; Miranti, Cindy K

2018-05-18

CD82 is a widely expressed member of the tetraspanin family of transmembrane proteins known to control cell signaling, adhesion, and migration. Tetraspanin CD82 is induced over 9-fold during osteoclast differentiation in vitro; however, its role in bone homeostasis is unknown. A globally deleted CD82 mouse model was used to assess the bone phenotype. Based on microCT and 4-point bending tests, CD82-deficient bones are smaller in diameter and weaker, but display no changes in bone density. Histomorphometry shows a decrease in size, erosion perimeter, and number of osteoclasts in situ, with a corresponding increase in trabecular surface area, specifically in male mice. Male-specific alterations are observed in trabecular structure by microCT and in vitro differentiated osteoclasts are morphologically abnormal. Histomorphometry did not reveal a significant reduction in osteoblast number; however, dynamic labeling reveals a significant decrease in bone growth. Consistent with defects in OB function, OB differentiation and mineralization are defective in vitro, whereas adipogenesis is enhanced. There is a corresponding increase in bone marrow adipocytes in situ. Thus, combined defects in both osteoclasts and osteoblasts can account for the observed bone phenotypes, and suggests a role for CD82 in both bone mesenchyme and myeloid cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Overshoot Convective Mixing in Nova Outbursts

NASA Astrophysics Data System (ADS)

Glasner, A. S.; Livne, E.; Truran, J. W.

2014-12-01

We present a 2D study of the overshoot convective mechanism in nova outbursts for a wide range of possible compositions of the layer underlying the accreted envelope. Previous surveys studied this mechanism only for solar composition matter accreted on top of carbon oxygen (CO) white dwarfs. Since, during the runaway, mixing with carbon enhances the hydrogen burning rates dramatically, one should question whether significant enrichment of the ejecta is possible also for other underlying compositions (He, O, Ne, Mg) predicted by stellar evolution models. When needed we upgraded our reaction network and simulated several non-carbon cases. Despite large differences in rates, time scales and energetics, our results show that the convective dredge up mechanism predicts significant enrichment in all cases, including that of helium enrichment in recurrent novae.

Asymmetric mass accretion in the magnetic cataclysmic variable RE 1149 + 28

NASA Technical Reports Server (NTRS)

Howell, Steve B.; Sirk, Martin M.; Malina, Roger F.; Mittaz, J. P. D.; Mason, K. O.

1995-01-01

We present the first detailed extreme photometric observations of a magnetic cataclysmic variable. Our two Extreme Ultraviolet Explorer (EUVE) observations of the AM Her star RE 1149 + 28 were obtained about 1 yr apart and show light-curve variations on orbital to yearly timescales, as well as long-term mean flux level changes of a factor of 2. The photometric data show a persistent ingress EUV enhancement which lasts approximately 0.04 in phase. We attribute this to a region of approximately 10(exp 3) km in extent at the accretion impact site, on or very near the surface of the white dwarf primary. Our observations of RE 1149 are consistent with a relatively low system inclination and provide a best-fit orbital period of 90.14 +/- 0.015 minutes.

The Formation of Terrestrial Planets from the Direct Accretion of Pebbles

NASA Astrophysics Data System (ADS)

Levison, Harold F.; Kretke, Katherine; Walsh, Kevin

2014-11-01

A radical new scenario has recently been suggested for the formation of giant planet cores that reports to solve this long-standing problem. This scenario, known as pebble accretion, envisions: 1) Planetesimals form directly from millimeter- to meter-sized objects (the pebbles) that are concentrated by turbulent eddies and then gravitationally collapse to form 100 — 1000 km objects (Cuzzi+ 2008, AJ 687, 1432; Johansen+ 2007, Nature 448, 1022). 2) These planetesimals quickly sweep up the remaining pebbles because their capture cross sections are significantly enhanced by aerodynamic drag (Lambrechts & Johansen 2012, A&A 544, A32; Ormel & Klahr (2010) A&A Volume 520, id.A43). Calculations show that a single 1000 km object embedded in a swarm of pebbles can grow to ~10 Earth-masses in less than 10,000 years. These short timescales present a problem in the terrestrial planet region because it took many tens of millions of years for the Earth to form (Touboul+ 2007, Nature 450, 1206). However, recent full-scale simulations of core formation have shown that the only way to grow a small number of giant planets in the Solar System is for the pebbles to form over a long period of time (Kretke & Levison 2014, AJ, submitted; Levison & Kretke in prep.) in a process we call 'Slow Pebble Accretion'. Thus, here we will present preliminary results of a study of slow pebble accretion in the terrestrial planet zone.

General Relativistic Effects and QPOs in X-Ray Binaries

NASA Astrophysics Data System (ADS)

Markovic, D.; Lamb, F.

1999-05-01

We have investigated whether general relativistic effects may be responsible for some of the quasi-periodic X-ray brightness oscillations (QPOs) with frequencies 20--300 Hz observed in low-mass binary systems containing accreting neutron stars and black hole candidates. In particular, we have computed the motions of accreting gas in the strong gravitational fields near such objects and have explored possible mechanisms for producing X-ray flux oscillations. We have discovered a family of global gravitomagnetic (Lense-Thirring) warping modes of the inner accretion disk that have precession frequencies ranging up to the single-particle gravitomagnetic precession frequency at the inner edge of the disk, which is 30 Hz if the disk extends inward to the innermost stable circular orbit around a compact object of solar mass with dimensionless angular momentum cJ/GM2 0.2. The highest-frequency warping modes are very localized spiral corrugations of the inner disk and are weakly damped, with Q values 2--50. Precession of regions of enhanced viscous dissipation or modulation of the accretion flow by the precession may produce observable periodic variation of the X-ray flux. Detectable effects might also be produced if the gas in the inner disk breaks up into a collection of distinct clumps. We have analyzed the dynamics of such clumps as well as the conditions required for their formation and survival on time scales long enough to produce oscillations with the coherence observed in X-ray binaries.

Marsh vertical accretion in a Southern California Estuary, U.S.A

USGS Publications Warehouse

Cahoon, D.R.; Lynch, J.C.; Powell, A.N.

1996-01-01

Vertical accretion was measured between October 1992 and March 1994 in low and high saltmarsh zones in the north arm of Tijuana estuary from feldspar market horizons and soil corings. Accretion in the Spartina foliosa low marsh (2-8.5 cm) was related almost entirely to episodic storm-induced river flows between January and March 1993, with daily tidal flooding contributing little or no sediment during the subsequent 12 month period of no river flow. Accretion in the Salicornia subterminalis high marsh was low (~1-2 mm) throughout the 17-month measuring period. High water levels in the salt marsh associated with the storm flows were enhanced in early January 1993 by the monthly extreme high sea level, when the low and high marshes were flooded about 0.5 m above normal high tide levels. Storm flows in January-March 1993 mobilized about 5 million tons of sediment, of which the low salt marsh trapped an estimated 31,941 tonnes, including 971 tonnes of carbon and 77 tonnes of nitrogen. Sediment trapping by the salt marsh during episodic winter floods plays an important role in the long-term maintenance of productivity of Tijuana estuary through nutrient retention and maintenance of marsh surface elevation. The potential exists, however, for predicted accelerated rates of sea-level rise to out-pace marsh surface elevation gain during extended periods of drought (i.e. low sediment inputs) which are not uncommon for this arid region.

DOES A DIFFERENTIATED, CARBONATE-RICH, ROCKY OBJECT POLLUTE THE WHITE DWARF SDSS J104341.53+085558.2?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melis, Carl; Dufour, P., E-mail: cmelis@ucsd.edu

We present spectroscopic observations of the dust- and gas-enshrouded, polluted, single white dwarf star SDSS J104341.53+085558.2 (hereafter SDSS J1043+0855). Hubble Space Telescope Cosmic Origins Spectrograph far-ultraviolet spectra combined with deep Keck HIRES optical spectroscopy reveal the elements C, O, Mg, Al, Si, P, S, Ca, Fe, and Ni and enable useful limits for Sc, Ti, V, Cr, and Mn in the photosphere of SDSS J1043+0855. From this suite of elements we determine that the parent body being accreted by SDSS J1043+0855 is similar to the silicate Moon or the outer layers of Earth in that it is rocky and iron-poor.more » Combining this with comparison to other heavily polluted white dwarf stars, we are able to identify the material being accreted by SDSS J1043+0855 as likely to have come from the outermost layers of a differentiated object. Furthermore, we present evidence that some polluted white dwarfs (including SDSS J1043+0855) allow us to examine the structure of differentiated extrasolar rocky bodies. Enhanced levels of carbon in the body polluting SDSS J1043+0855 relative to the Earth–Moon system can be explained with a model where a significant amount of the accreted rocky minerals took the form of carbonates; specifically, through this model the accreted material could be up to 9% calcium-carbonate by mass.« less

Marsh Vertical Accretion in a Southern California Estuary, U.S.A.

NASA Astrophysics Data System (ADS)

Cahoon, Donald R.; Lynch, James C.; Powell, Abby N.

1996-07-01

Vertical accretion was measured between October 1992 and March 1994 in low and high saltmarsh zones in the north arm of Tijuana estuary from feldspar market horizons and soil corings. Accretion in the Spartina foliosalow marsh (2-8·5 cm) was related almost entirely to episodic storm-induced river flows between January and March 1993, with daily tidal flooding contributing little or no sediment during the subsequent 12-month period of no river flow. Accretion in the Salicornia subterminalishigh marsh was low (≈1-2 mm) throughout the 17-month measuring period. High water levels in the salt marsh associated with the storm flows were enhanced in early January 1993 by the monthly extreme high sea level, when the low and high marshes were flooded about 0·5 m above normal high tide levels. Storm flows in January-March 1993 mobilized about 5 million tonnes of sediment, of which the low salt marsh trapped an estimated 31 941 tonnes, including 971 tonnes of carbon and 77 tonnes of nitrogen. Sediment trapping by the salt marsh during episodic winter floods plays an important role in the long-term maintenance of productivity of Tijuana estuary through nutrient retention and maintenance of marsh surface elevation. The potential exists, however, for predicted accelerated rates of sea-level rise to out-pace marsh surface elevation gain during extended periods of drought (i.e. low sediment inputs) which are not uncommon for this arid region.

Transient gamma-secretase inhibition accelerates and enhances fracture repair likely via Notch signaling modulation

PubMed Central

Wang, Cuicui; Shen, Jie; Yukata, Kiminori; Inzana, Jason A.; O'Keefe, Regis J.; Awad, Hani A.; Hilton, Matthew J.

2014-01-01

Approximately 10% of skeletal fractures result in healing complications and non-union, while most fractures repair with appropriate stabilization and without pharmacologic intervention. It is the latter injuries that cannot be underestimated as the expenses associated with their treatment and subsequent lost productivity are predicted to increase to over $74 billion by 2015. During fracture repair, local mesenchymal stem/progenitor cells (MSCs) differentiate to form new cartilage and bone, reminiscent of events during skeletal development. We previously demonstrated that permanent loss of gamma-secretase activity and Notch signaling accelerates bone and cartilage formation from MSC progenitors during skeletal development, leading to pathologic acquisition of bone and depletion of bone marrow derived MSCs. Here, we investigated whether transient and systemic gamma-secretase and Notch inhibition is capable of accelerating and enhancing fracture repair by promoting controlled MSC differentiation near the fracture site. Our radiographic, microCT, histological, cell and molecular analyses reveal that single and intermittent gamma-secretase inhibitor (GSI) treatments significantly enhance cartilage and bone callus formation via the promotion of MSC differentiation, resulting in only a moderate reduction of local MSCs. Biomechanical testing further demonstrates that GSI treated fractures exhibit superior strength earlier in the healing process, with single dose GSI treated fractures exhibiting bone strength approaching that of un-fractured tibiae. These data further establish that transient inhibition of gamma-secretase activity and Notch signaling temporarily increases osteoclastogenesis and accelerates bone remodeling, which coupled with the effects on MSCs likely explains the accelerated and enhanced fracture repair. Therefore, we propose that the Notch pathway serves as an important therapeutic target during skeletal fracture repair. PMID:25527421

Heterodimeric BMP-2/7 Antagonizes the Inhibition of All-Trans Retinoic Acid and Promotes the Osteoblastogenesis

PubMed Central

Bi, Wenjuan; Gu, Zhiyuan; Zheng, Yuanna; Zhang, Xiao; Guo, Jing; Wu, Gang

2013-01-01

Objectives Hypervitaminosis A and alcoholism can result in a low mineral density and compromised regenerative capacity of bone, thus delaying implant osteointegration. The inhibitory effect of all-trans retinoic acid on osteoblastogenesis is considered to be one of the mechanisms. We hypothesized that heterodimeric bone morphogenetic protein-2/7 could antagonize all-trans retinoic acid and enhance osteoblastogenesis, with an aim to accelerate and enhance bone regeneration and implant osteointegration. Materials and Methods We applied 5 ng/ml or 50 ng/ml bone morphogenetic protein-2/7 to restore the osteoblastogenesis of pre-osteoblasts (MC3T3-E1 cell line) that was inhibited by 1 µM all-trans retinoic acid. We evaluated the efficacy by assessing cell numbers (proliferation), alkaline phosphatase activity (a marker for early differentiation), osteocalcin (a marker for late differentiation), calcium deposition (a marker for final mineralization) and the expression of osteoblastogenic genes (such as Runx2, Collagen Ia, alkaline phosphatase and osteocalcin) at different time points. Results All-trans retinoic acid significantly inhibited the expression of all the tested osteoblastogenic genes and proteins except alkaline phosphatase activity. In the presence of ATRA, 50 ng/ml bone morphogenetic protein-2/7 not only completely restored but also significantly enhanced all the osteoblastogenic genes and proteins. On the 28th day, mineralization was completely inhibited by all-trans retinoic acid. In contrast, 50 ng/ml BMP-2/7 could antagonize ATRA and significantly enhance the mineralization about 2.5 folds in comparison with the control treatment (no ATRA, no BMP2/7). Conclusions Heterodimeric bone morphogenetic protein-2/7 bears a promising application potential to significantly promote bone regeneration and implant osteointegration for the patients with hypervitaminosis A and alcoholism. PMID:24205156

Calcium and bone health in children: a review.

PubMed

Stallings, V A

1997-01-01

The recent national survey shows that dietary calcium intake is variable in children and adolescents, with about half consuming less than the intake recommended by the Recommended Dietary Allowances or the National Institutes of Health Consensus Panel on Optimal Calcium Intake. Osteoporosis is a major disease in adults, resulting in 1.5 million fractures and over $10 billion in medical expenditures annually. Osteoporosis is of growing interest in the research, public health, and health consumer-lay communities and to the many primary care and specialty physicians and other health care professionals who work directly with patients with osteoporosis. Treatment of osteoporosis to prevent fracture is improving with newly introduced medications and approaches, but it is not as effective as needed. Effective prevention strategies are critical to decreasing the morbidity and mortality of the disease. Peak bone mass, obtained during childhood and adolescent growth, is one of the major determinants for the risk of developing osteoporosis and fracture. Genetic potential, gender, ethnic origins, nutritional factors such as calcium and vitamin D intake, growth patterns, and physical activity influence the accretion of bone mineral during childhood and determine the peak bone mass. Randomized, placebo-controlled intervention trials conducted in healthy children who are consuming amounts of dietary calcium in accordance with the US recommendations show that bone mass can be increased by calcium supplementation. Retrospective studies in adults suggest that childhood calcium intake is associated with risk of later osteoporosis and fracture. In addition, common childhood clinical conditions, such as low calcium intake related to lactose intolerance or the use of glucocorticoid medications for chronic illness, are risk factors for the development of osteoporosis in childhood, not just in adulthood. An approach for physicians and other pediatric care providers for screening children for low dietary calcium intake, low bone density, and other osteoporosis risk factors using dual-energy X-ray absorptiometry and the use of calcium supplementation in clinical care are presented.

Classification of non-union.

PubMed

Megas, Panagiotis; Panagiotis, Megas

2005-11-01

A substantial number of experimental and clinical studies have established that the cornerstones for successful bone-healing are biomechanical stability and biological vitality of the bone, as they both provide an environment in which new bone can be formed. Non-union of long bones is a significant consequence in treating fractures. Many approaches to prevent fracture non-union have been proposed. Depending on the type and location of the non-union, treatment options include various types of bone fixation, with or without supplemental bone graft or other biophysical enhancements.

Multipurpose contrast enhancement on epiphyseal plates and ossification centers for bone age assessment

PubMed Central

2013-01-01

Background The high variations of background luminance, low contrast and excessively enhanced contrast of hand bone radiograph often impede the bone age assessment rating system in evaluating the degree of epiphyseal plates and ossification centers development. The Global Histogram equalization (GHE) has been the most frequently adopted image contrast enhancement technique but the performance is not satisfying. A brightness and detail preserving histogram equalization method with good contrast enhancement effect has been a goal of much recent research in histogram equalization. Nevertheless, producing a well-balanced histogram equalized radiograph in terms of its brightness preservation, detail preservation and contrast enhancement is deemed to be a daunting task. Method In this paper, we propose a novel framework of histogram equalization with the aim of taking several desirable properties into account, namely the Multipurpose Beta Optimized Bi-Histogram Equalization (MBOBHE). This method performs the histogram optimization separately in both sub-histograms after the segmentation of histogram using an optimized separating point determined based on the regularization function constituted by three components. The result is then assessed by the qualitative and quantitative analysis to evaluate the essential aspects of histogram equalized image using a total of 160 hand radiographs that are implemented in testing and analyses which are acquired from hand bone online database. Result From the qualitative analysis, we found that basic bi-histogram equalizations are not capable of displaying the small features in image due to incorrect selection of separating point by focusing on only certain metric without considering the contrast enhancement and detail preservation. From the quantitative analysis, we found that MBOBHE correlates well with human visual perception, and this improvement shortens the evaluation time taken by inspector in assessing the bone age. Conclusions The proposed MBOBHE outperforms other existing methods regarding comprehensive performance of histogram equalization. All the features which are pertinent to bone age assessment are more protruding relative to other methods; this has shorten the required evaluation time in manual bone age assessment using TW method. While the accuracy remains unaffected or slightly better than using unprocessed original image. The holistic properties in terms of brightness preservation, detail preservation and contrast enhancement are simultaneous taken into consideration and thus the visual effect is contributive to manual inspection. PMID:23565999

Bone grafts.

PubMed

Hubble, Matthew J W

2002-09-01

Bone grafts are used in musculoskeletal surgery to restore structural integrity and enhance osteogenic potential. The demand for bone graft for skeletal reconstruction in bone tumor, revision arthroplasty, and trauma surgery, couple with recent advances in understanding and application of the biology of bone transplantation, has resulted in an exponential increase in the number of bone-grafting procedures performed over the last decade. It is estimated that 1.5 million bone-grafting procedures are currently performed worldwide each year, compared to a fraction of that number 20 years ago. Major developments also have resulted in the harvesting, storage, and use of bone grafts and production of graft derivatives, substitutes, and bone-inducing agents.

[Impact of thyroid diseases on bone].

PubMed

Tsourdi, E; Lademann, F; Siggelkow, H

2018-05-09

Thyroid hormones are key regulators of skeletal development in childhood and bone homeostasis in adulthood, and thyroid diseases have been associated with increased osteoporotic fractures. Hypothyroidism in children leads to an impaired skeletal maturation and mineralization, but an adequate and timely substitution with thyroid hormones stimulates bone growth. Conversely, hyperthyroidism at a young age accelerates skeletal development, but may also cause short stature because of a premature fusion of the growth plates. Hypothyroidism in adults causes an increase in the duration of the remodeling cycle and, thus, leads to low bone turnover and enhanced mineralization, but an association with a higher fracture risk is less well established. In adults, a surplus of thyroid hormones enhances bone turnover, mostly due to an increased bone resorption driven by osteoclasts. Thus, hyperthyroidism is a well-recognized cause of high-bone turnover secondary osteoporosis, resulting in an increased susceptibility to fragility fractures. Subclinical hyperthyroidism, especially resulting from endogenous disease, also has an adverse effect on bone mineral density and is associated with fractures. In most patients with overt or subclinical hyperthyroidism restoration of the euthyroid status reverses bone loss. In postmenopausal women who receive thyroid-stimulating hormone suppression therapy because of thyroid cancer, antiresorptive treatments may be indicated. Overall, extensive data support the importance of a euthyroid status for bone mineral accrual and growth in childhood as well as maintenance of bone health in adulthood.

A crucial role for thiol antioxidants in estrogen-deficiency bone loss

PubMed Central

Lean, Jenny M.; Davies, Julie T.; Fuller, Karen; Jagger, Christopher J.; Kirstein, Barrie; Partington, Geoffrey A.; Urry, Zoë L.; Chambers, Timothy J.

2003-01-01

The mechanisms through which estrogen prevents bone loss are uncertain. Elsewhere, estrogen exerts beneficial actions by suppression of reactive oxygen species (ROS). ROS stimulate osteoclasts, the cells that resorb bone. Thus, estrogen might prevent bone loss by enhancing oxidant defenses in bone. We found that glutathione and thioredoxin, the major thiol antioxidants, and glutathione and thioredoxin reductases, the enzymes responsible for maintaining them in a reduced state, fell substantially in rodent bone marrow after ovariectomy and were rapidly normalized by exogenous 17-β estradiol. Moreover, administration of N-acetyl cysteine (NAC) or ascorbate, antioxidants that increase tissue glutathione levels, abolished ovariectomy-induced bone loss, while L-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of glutathione synthesis, caused substantial bone loss. The 17-β estradiol increased glutathione and glutathione and thioredoxin reductases in osteoclast-like cells in vitro. Furthermore, in vitro NAC prevented osteoclast formation and NF-κB activation. BSO and hydrogen peroxide did the opposite. Expression of TNF-α, a target for NF-κB and a cytokine strongly implicated in estrogen-deficiency bone loss, was suppressed in osteoclasts by 17-β estradiol and NAC. These observations strongly suggest that estrogen deficiency causes bone loss by lowering thiol antioxidants in osteoclasts. This directly sensitizes osteoclasts to osteoclastogenic signals and entrains ROS-enhanced expression of cytokines that promote osteoclastic bone resorption. PMID:12975476

Ice Accretions and Full-Scale Iced Aerodynamic Performance Data for a Two-Dimensional NACA 23012 Airfoil

NASA Technical Reports Server (NTRS)

Addy, Harold E., Jr.; Broeren, Andy P.; Potapczuk, Mark G.; Lee, Sam; Guffond, Didier; Montreuil, Emmanuel; Moens, Frederic

2016-01-01

This report documents the data collected during the large wind tunnel campaigns conducted as part of the SUNSET project (StUdies oN Scaling EffecTs due to ice) also known as the Ice-Accretion Aerodynamics Simulation study: a joint effort by NASA, the Office National d'Etudes et Recherches Aérospatiales (ONERA), and the University of Illinois. These data form a benchmark database of full-scale ice accretions and corresponding ice-contaminated aerodynamic performance data for a two-dimensional (2D) NACA 23012 airfoil. The wider research effort also included an analysis of ice-contaminated aerodynamics that categorized ice accretions by aerodynamic effects and an investigation of subscale, low- Reynolds-number ice-contaminated aerodynamics for the NACA 23012 airfoil. The low-Reynolds-number investigation included an analysis of the geometric fidelity needed to reliably assess aerodynamic effects of airfoil icing using artificial ice shapes. Included herein are records of the ice accreted during campaigns in NASA Glenn Research Center's Icing Research Tunnel (IRT). Two different 2D NACA 23012 airfoil models were used during these campaigns; an 18-in. (45.7-cm) chord (subscale) model and a 72-in. (182.9-cm) chord (full-scale) model. The aircraft icing conditions used during these campaigns were selected from the Federal Aviation Administration's (FAA's) Code of Federal Regulations (CFR) Part 25 Appendix C icing envelopes. The records include the test conditions, photographs of the ice accreted, tracings of the ice, and ice depth measurements. Model coordinates and pressure tap locations are also presented. Also included herein are the data recorded during a wind tunnel campaign conducted in the F1 Subsonic Pressurized Wind Tunnel of ONERA. The F1 tunnel is a pressured, high- Reynolds-number facility that could accommodate the full-scale (72-in. (182.9-cm) chord) 2D NACA 23012 model. Molds were made of the ice accreted during selected test runs of the full-scale model in the IRT. From these molds, castings were made that closely replicated the features of the accreted ice. The castings were then mounted on the full-scale model in the F1 tunnel, and aerodynamic performance measurements were made using model surface pressure taps, the facility force balance system, and a large wake rake designed specifically for these tests. Tests were run over a range of Reynolds and Mach numbers. For each run, the model was rotated over a range of angles-of-attack that included airfoil stall. The benchmark data collected during these campaigns were, and continue to be, used for various purposes. The full-scale data form a unique, ice-accretion and associated aerodynamic performance dataset that can be used as a reference when addressing concerns regarding the use of subscale ice-accretion data to assess full-scale icing effects. Further, the data may be used in the development or enhancement of both ice-accretion prediction codes and computational fluid dynamic codes when applied to study the effects of icing. Finally, as was done in the wider study, the data may be used to help determine the level of geometric fidelity needed for artificial ice used to assess aerodynamic degradation due to aircraft icing. The structured, multifaceted approach used in this research effort provides a unique perspective on the aerodynamic effects of aircraft icing. The data presented in this report are available in electronic form upon formal approval by proper NASA and ONERA authorities.

Simulations of recoiling black holes: adaptive mesh refinement and radiative transfer

NASA Astrophysics Data System (ADS)

Meliani, Zakaria; Mizuno, Yosuke; Olivares, Hector; Porth, Oliver; Rezzolla, Luciano; Younsi, Ziri

2017-02-01

Context. In many astrophysical phenomena, and especially in those that involve the high-energy regimes that always accompany the astronomical phenomenology of black holes and neutron stars, physical conditions that are achieved are extreme in terms of speeds, temperatures, and gravitational fields. In such relativistic regimes, numerical calculations are the only tool to accurately model the dynamics of the flows and the transport of radiation in the accreting matter. Aims: We here continue our effort of modelling the behaviour of matter when it orbits or is accreted onto a generic black hole by developing a new numerical code that employs advanced techniques geared towards solving the equations of general-relativistic hydrodynamics. Methods: More specifically, the new code employs a number of high-resolution shock-capturing Riemann solvers and reconstruction algorithms, exploiting the enhanced accuracy and the reduced computational cost of adaptive mesh-refinement (AMR) techniques. In addition, the code makes use of sophisticated ray-tracing libraries that, coupled with general-relativistic radiation-transfer calculations, allow us to accurately compute the electromagnetic emissions from such accretion flows. Results: We validate the new code by presenting an extensive series of stationary accretion flows either in spherical or axial symmetry that are performed either in two or three spatial dimensions. In addition, we consider the highly nonlinear scenario of a recoiling black hole produced in the merger of a supermassive black-hole binary interacting with the surrounding circumbinary disc. In this way, we can present for the first time ray-traced images of the shocked fluid and the light curve resulting from consistent general-relativistic radiation-transport calculations from this process. Conclusions: The work presented here lays the ground for the development of a generic computational infrastructure employing AMR techniques to accurately and self-consistently calculate general-relativistic accretion flows onto compact objects. In addition to the accurate handling of the matter, we provide a self-consistent electromagnetic emission from these scenarios by solving the associated radiative-transfer problem. While magnetic fields are currently excluded from our analysis, the tools presented here can have a number of applications to study accretion flows onto black holes or neutron stars.

Enhancement of osteogenesis and biodegradation control by brushite coating on Mg-Nd-Zn-Zr alloy for mandibular bone repair.

PubMed

Guan, Xingmin; Xiong, Meiping; Zeng, Feiyue; Xu, Bin; Yang, Lingdi; Guo, Han; Niu, Jialin; Zhang, Jian; Chen, Chenxin; Pei, Jia; Huang, Hua; Yuan, Guangyin

2014-12-10

To diminish incongruity between bone regeneration and biodegradation of implant magnesium alloy applied for mandibular bone repair, a brushite coating was deposited on a matrix of a Mg-Nd-Zn-Zr (hereafter, denoted as JDBM) alloy to control the degradation rate of the implant and enhance osteogenesis of the mandible bone. Both in vitro and in vivo evaluations were carried out in the present work. Viability and adhesion assays of rabbit bone marrow mesenchyal stem cells (rBM-MSCs) were applied to determine the biocompatibility of a brushite-coated JDBM alloy. Osteogenic gene expression was characterized by quantitative real-time polymerase chain reaction (RT-PCR). Brushite-coated JDBM screws were implanted into mandible bones of rabbits for 1, 4, and 7 months, respectively, using 316L stainless steel screws as a control group. In vivo biodegradation rate was determined by synchrotron radiation X-ray microtomography, and osteogenesis was observed and evaluated using Van Gieson's picric acid-fuchsin. Both the naked JDBM and brushite-coated JDBM samples revealed adequate biosafety and biocompatibility as bone repair substitutes. In vitro results showed that brushite-coated JDBM considerably induced osteogenic differentiation of rBM-MSCs. And in vivo experiments indicated that brushite-coated JDBM screws presented advantages in osteoconductivity and osteogenesis of mandible bone of rabbits. Degradation rate was suppressed at a lower level at the initial stage of implantation when new bone tissue formed. Brushite, which can enhance oeteogenesis and partly control the degradation rate of an implant, is an appropriate coating for JDBM alloys used for mandibular repair. The Mg-Nd-Zn-Zr alloy with brushite coating possesses great potential for clinical applications for mandibular repair.

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

PubMed Central

Sato, Ayako; Kajiya, Hiroshi; Mori, Nana; Sato, Hironobu; Fukushima, Tadao; Kido, Hirofumi

2017-01-01

The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration. PMID:28060874

Positive modulator of bone morphogenic protein-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Positive modulator of bone morphogenic protein-2

DOEpatents

Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

2009-01-27

Compounds of the present invention of formula I and formula II are disclosed in the specification and wherein the compounds are modulators of Bone Morphogenic Protein activity. Compounds are synthetic peptides having a non-growth factor heparin binding region, a linker, and sequences that bind specifically to a receptor for Bone Morphogenic Protein. Uses of compounds of the present invention in the treatment of bone lesions, degenerative joint disease and to enhance bone formation are disclosed.

Noni leaf and black tea enhance bone regeneration in estrogen-deficient rats.

PubMed

Shalan, Nor Aijratul Asikin Mohd; Mustapha, Noordin M; Mohamed, Suhaila

2017-01-01

Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats. Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh). The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density. The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women. Copyright © 2016 Elsevier Inc. All rights reserved.

IL-12p40 impairs mesenchymal stem cell-mediated bone regeneration via CD4+ T cells

PubMed Central

Xu, Jiajia; Wang, Yiyun; Li, Jing; Zhang, Xudong; Geng, Yiyun; Huang, Yan; Dai, Kerong; Zhang, Xiaoling

2016-01-01

Severe or prolonged inflammatory response caused by infection or biomaterials leads to delayed healing or bone repair failure. This study investigated the important roles of the proinflammatory cytokines of the interleukin-12 (IL-12) family, namely, IL-12 and IL-23, in the inflammation-mediated inhibition of bone formation in vivo. IL-12p40−/− mice lacking IL-12 and IL-23 exhibited enhanced bone formation. IL-12 and IL-23 indirectly inhibited bone marrow mesenchymal stem cell (BMMSC) differentiation by stimulating CD4+ T cells to increase interferon γ (IFN-γ) and IL-17 levels. Mechanistically, IL-17 synergistically enhanced IFN-γ-induced BMMSC apoptosis. Moreover, INF-γ and IL-17 exerted proapoptotic effects by upregulating the expression levels of Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as well as by activating the caspase cascade in BMMSCs. IL-12p40 depletion in mice could promote ectopic bone formation. Thus, IL-12p40 is an attractive therapeutic target to overcome the inflammation-mediated inhibition of bone formation in vivo. PMID:27472064

Local Bisphosphonate Treatment Increases Fixation of Hydroxyapatite-Coated Implants Inserted with Bone Compaction

PubMed Central

Jakobsen, Thomas; Baas, Jørgen; Kold, Søren; Bechtold, Joan E.; Elmengaard, Brian; Søballe, Kjeld

2013-01-01

It has been shown that fixation of primary cementless joint replacement can independently be enhanced by either: (1) use of hydroxyapatite (HA) coated implants, (2) compaction of the peri-implant bone, or (3) local application of bisphosphonate. We investigated whether the combined effect ofHAcoating and bone compaction can be further enhanced with the use of local bisphosphonate treatment .HA-coated implants were bilaterally inserted into the proximal tibiae of 10 dogs. On one side local bisphosphonate was applied prior to bone compaction. Saline was used as control on the contralateral side. Implants were evaluated with histomorphometry and biomechanical pushout test. We found that bisphosphonate increased the peri-implant bone volume fraction (1.3-fold), maximum shear strength (2.1-fold), and maximum shear stiffness (2.7-fold). No significant difference was found in bone-to-implant contact or total energy absorption. This study indicates that local alendronate treatment can further improve the fixation of porous-coated implants that have also undergone HA-surface coating and peri-implant bone compaction. PMID:18752278

ATF4 mediation of NF1 functions in osteoblast reveals a nutritional basis for congenital skeletal dysplasiae

PubMed Central

Elefteriou, Florent; Benson, M. Douglas; Sowa, Hideaki; Starbuck, Michael; Liu, Xiuyun; Ron, David; Parada, Luis F.; Karsenty, Gerard

2009-01-01

Summary The transcription factor ATF4 enhances bone formation by favoring amino acid import and collagen synthesis in osteoblasts, a function requiring its phosphorylation by RSK2, the kinase inactivated in Coffin-Lowry Syndrome. Here, we show that in contrast, RSK2 activity, ATF4-dependent collagen synthesis, and bone formation are increased in mice lacking neurofibromin in osteoblasts (Nf1ob−/− mice). Independently of RSK2, ATF4 phosphorylation by PKA is enhanced in Nf1ob−/− mice, thereby increasing Rankl expression, osteoclast differentiation, and bone resorption. In agreement with ATF4 function in amino acid transport, a low-protein diet decreased bone protein synthesis and normalized bone formation and bone mass in Nf1ob−/− mice without affecting other organ weight, while a high-protein diet overcame Atf4−/− and Rsk2−/− mice developmental defects, perinatal lethality, and low bone mass. By showing that ATF4-dependent skeletal dysplasiae are treatable by dietary manipulations, this study reveals a molecular connection between nutrition and skeletal development. PMID:17141628

Size Segregation and Number Density Enhancement of Particles in Accretion Disk Eddies

NASA Technical Reports Server (NTRS)

Klahr, H. H.; Henning, Th.

1996-01-01

We investigate the conditions for trapping solid dust particles in eddies and discuss the behavior of particles in a non-laminar protoplanetary accretion disk. We considered particle sizes from small dust grains to larger objects, 10(exp -4) cm less than a(sub p) less than 10(exp 2) cm. Independent of the source of turbulence, one can expect eddies to exist in the gas flow of a accretion disk, in the form of randomly occurring turbulent features or as convective cells. Due to the centrifugal force, solid particles are driven out of an eddy. It will be shown that this process is inhibited by the gravitational force induced by the protostar. Because of the mass dependence of the friction time, a given eddy becomes a trap for particles of a characteristic size and causes a local change in the dust density. Thus, the size distribution of the grains is no longer spatially homogeneous on small scales. Our general estimates do not depend on special turbulence or convection models. We calculate the maximal inhomogeneity due to this process. The strongest effect was observed for mm-sized particles, which can be concentrated by a factor of 100 within only 100 years.

Local Thermonuclear Runaways in Dwarf Novae?

NASA Astrophysics Data System (ADS)

Shara, Michael

2012-10-01

We have no hope of understanding the structure and evolution of a class of astrophysical objects if we cannot identify the dominant energy source of those objects.The Disk Instability Model {DIM} postulates that Dwarf Nova {DN} outbursts are powered by runaway accretion from an accretion disk onto a White Dwarf {WD} in a red dwarf-WD mass transferring binary. Ominously, HST observations {e.g. Sion et al. 2001} of WD surface abundances hint at a significant shortcoming of the DIM. The data from the present proposal will be able to unequivocally demonstrate if the observed highly Carbon-depleted and Nitrogen-enhanced abundances on WD surfaces {NOT predicted by DIM} vary with binary orbital phase, or throughout a DN quiescence cycle, or from cycle to cycle. These same data will test if predicted {but never observed} Local Thermonuclear Runaways {"Nuclear-powered mini-novas"} occur on the WDs of DN. Such events could trigger or even power DN, providing the long-sought physical mechanism of DN eruptions that DIM lacks. As a "free" bonus, the same data may also directly detect the diffusion of accreted metals in a WD atmosphere for the first time, or provide significant limits on the diffusion rate.

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia.

PubMed

Mayurasakorn, Korapat; Williams, Jill J; Ten, Vadim S; Deckelbaum, Richard J

2011-03-01

With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between presynaptic and postsynaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing antiapoptotic activities such as decreasing responses to reactive oxygen species, upregulating antiapoptotic protein expression, downregulating apoptotic protein expression, and maintaining mitochondrial integrity and function. DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression.

Influence of tidal range on the stability of coastal marshland

USGS Publications Warehouse

Kirwan, Matthew L.; Guntenspergen, Glenn R.

2010-01-01

Early comparisons between rates of vertical accretion and sea level rise across marshes in different tidal ranges inspired a paradigm that marshes in high tidal range environments are more resilient to sea level rise than marshes in low tidal range environments. We use field-based observations to propose a relationship between vegetation growth and tidal range and to adapt two numerical models of marsh evolution to explicitly consider the effect of tidal range on the response of the marsh platform channel network system to accelerating rates of sea level rise. We find that the stability of both the channel network and vegetated platform increases with increasing tidal range. Our results support earlier hypotheses that suggest enhanced stability can be directly attributable to a vegetation growth range that expands with tidal range. Accretion rates equilibrate to the rate of sea level rise in all experiments regardless of tidal range, suggesting that comparisons between accretion rate and tidal range will not likely produce a significant relationship. Therefore, our model results offer an explanation to widely inconsistent field-based attempts to quantify this relationship while still supporting the long-held paradigm that high tidal range marshes are indeed more stable.

Star Clusters within FIRE

NASA Astrophysics Data System (ADS)

Perez, Adrianna; Moreno, Jorge; Naiman, Jill; Ramirez-Ruiz, Enrico; Hopkins, Philip F.

2017-01-01

In this work, we analyze the environments surrounding star clusters of simulated merging galaxies. Our framework employs Feedback In Realistic Environments (FIRE) model (Hopkins et al., 2014). The FIRE project is a high resolution cosmological simulation that resolves star forming regions and incorporates stellar feedback in a physically realistic way. The project focuses on analyzing the properties of the star clusters formed in merging galaxies. The locations of these star clusters are identified with astrodendro.py, a publicly available dendrogram algorithm. Once star cluster properties are extracted, they will be used to create a sub-grid (smaller than the resolution scale of FIRE) of gas confinement in these clusters. Then, we can examine how the star clusters interact with these available gas reservoirs (either by accreting this mass or blowing it out via feedback), which will determine many properties of the cluster (star formation history, compact object accretion, etc). These simulations will further our understanding of star formation within stellar clusters during galaxy evolution. In the future, we aim to enhance sub-grid prescriptions for feedback specific to processes within star clusters; such as, interaction with stellar winds and gas accretion onto black holes and neutron stars.

Low-intensity pulsed ultrasound enhances healing of laminectomy chip bone grafts on spinal fusion: a model of posterolateral intertransverse fusion in rabbits.

PubMed

Liao, Jen-Chung; Chen, Wen-Jer; Chen, Lih-Hui; Lai, Po-Liang; Keorochana, Gun

2011-04-01

Laminectomy-derived chip bone graft was usually used in spinal fusion; however, the result of this kind of local bone used in lumbar posterolateral fusion is uncertain. This study tested the hypotheses that low-intensity pulsed ultrasound (LIPU) can accelerate the healing process of laminectomy bone chips in a spinal fusion and enhance the union rate. Forty-eight rabbits were randomly divided into three groups for the spinal unilateral uninstrumented posterolateral fusion of L5-L6: autologous iliac bone graft (AIBG), laminectomy chip bone graft (LCBG), LCBG plus LIPU (LCBG + LIPU). Each group was subdivided into 6-week and 12-week subgroups. All rabbits were subjected to radiographic examination and manual testing. All successful spinal fusion specimens received biomechanical testing and a histologic examination. The LCBG + LIPU group had the highest successful fusion rate at 6-week and 12-week examination (75% and 100%, respectively). At 6 weeks, the average maximum toque at failure values of the fusion masses for the LCBG + LIPU group was significantly higher than that for the LCBG group (p = 0.034). The average maximum torque of the 12-week LCBG + LIPU group was significantly higher than those of the 12-week AIBG and 12-week LCBG groups (p = 0.040 and p = 0.026, respectively). This study suggested that LIPU can enhance bone healing. With augmentation by LIPU, laminectomy chip bone used in lumbar posterolateral fusion can achieve a similar fusion rate and stronger fusion mass than those of an AIBG.

Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sisti, Karin E., E-mail: karinellensisti@gmail.com; Biomaterials Group, Institute of Chemistry, São Paulo State University; Federal University of Mato Grosso do Sul

Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv)more » LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell morphology and cytoskeleton structure were affected. The current studies show Ti LASER modification can enhance the osseointegration between Ti and skeletal cells, with important implications for orthopaedic application. - Highlights: • Bone stem cells on LASER Ti surface display enhanced cell growth and viability. • Bone stem cells on LASER Ti surface exhibit marked biocompatibility. • Human bone stem cells on LASER Ti surface exhibit altered morphology. • LASER Ti enhance osteogenic differentiation of human bone skeletal stem cells. • LASER Ti provides a unique approach to enhance osseointegration with the material.« less

The effect of layer-by-layer chitosan-hyaluronic acid coating on graft-to-bone healing of a poly(ethylene terephthalate) artificial ligament.

PubMed

Li, Hong; Ge, Yunsheng; Zhang, Pengyun; Wu, Lingxiang; Chen, Shiyi

2012-01-01

Surface coating with an organic layer-by-layer self-assembled template of chitosan and hyaluronic acid on a poly(ethylene terephthalate) (PET) artificial ligament was designed for the promotion and enhancement of graft-to-bone healing after artificial ligament implantation in a bone tunnel. The results of in vitro culturing of MC3T3-E1 mouse osteoblastic cells supported the hypothesis that the layer-by-layer coating of chitosan and hyaluronic acid could promote the cell compatibility of grafts and could promote osteoblast proliferation. A rabbit extra-articular tendon-to-bone healing model was used to evaluate the effect of this kind of surface-modified stainless artificial ligament in vivo. The final results proved that this organic compound coating could significantly promote and enhance new bone formation at the graft-bone interface histologically and, correspondingly, the experimental group with coating had significantly higher biomechanical properties compared with controls at 8 weeks (P < 0.05).

Micropore-induced Capillarity Enhances Bone Distribution in vivo in Biphasic Calcium Phosphate Scaffolds

PubMed Central

Rustom, Laurence E.; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W.; Lu, Yan; Markel, Mark D.; Picart, Catherine; Wagoner Johnson, Amy J.

2016-01-01

The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF¯, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF¯ of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. PMID:27544807

Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

PubMed Central

Crane, Janet L.; Cao, Xu

2013-01-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

Function of matrix IGF-1 in coupling bone resorption and formation.

PubMed

Crane, Janet L; Cao, Xu

2014-02-01

Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

Accelerated and enhanced bone formation on novel simvastatin-loaded porous titanium oxide surfaces.

PubMed

Nyan, Myat; Hao, Jia; Miyahara, Takayuki; Noritake, Kanako; Rodriguez, Reena; Kasugai, Shohei

2014-10-01

With increasing application of dental implants in poor-quality bones, the need for implant surfaces ensuring accelerated osseointegration and enhanced peri-implant bone regeneration is increased. A study was performed to evaluate the osseointegration and bone formation on novel simvastatin-loaded porous titanium oxide surface. Titanium screws were treated by micro-arc oxidation to form porous oxide surface and 25 or 50 μg of simvastatin was loaded. The nontreated control, micro-arc oxidized, and simvastatin-loaded titanium screws were surgically implanted into the proximal tibia of 16-week-old male Wistar rats (n = 36). Peri-implant bone volume, bone-implant contact, and mineral apposition rates were measured at 2 and 4 weeks. Data were analyzed by one-way analysis of variance followed by Tukey's post hoc test. New bone was formed directly on the implant surface in the bone marrow cavity in simvastatin-loaded groups since 2 weeks. Bone-implant contact values were significantly higher in simvastatin-loaded groups than control and micro-arc oxidized groups at both time points (p < .05). Peri-implant bone volume and mineral apposition rate of simvastatin-loaded groups were significantly higher than control and micro-arc oxidized groups at 2 weeks (p < .05). These data suggested that simvastatin-loaded porous titanium oxide surface provides faster osseointegration and peri-implant bone formation and it would be potentially applicable in poor-quality bones. © 2013 Wiley Periodicals, Inc.

Impact of convection and resistivity on angular momentum transport in dwarf novae

NASA Astrophysics Data System (ADS)

Scepi, N.; Lesur, G.; Dubus, G.; Flock, M.

2018-01-01

The eruptive cycles of dwarf novae are thought to be due to a thermal-viscous instability in the accretion disk surrounding the white dwarf. This model has long been known to imply enhanced angular momentum transport in the accretion disk during outburst. This is measured by the stress to pressure ratio α, with α ≈ 0.1 required in outburst compared to α ≈ 0.01 in quiescence. Such an enhancement in α has recently been observed in simulations of turbulent transport driven by the magneto-rotational instability (MRI) when convection is present, without requiring a net magnetic flux. We independently recover this result by carrying out PLUTO magnetohydrodynamic (MHD) simulations of vertically stratified, radiative, shearing boxes with the thermodynamics and opacities appropriate to dwarf novae. The results are robust against the choice of vertical boundary conditions. The thermal equilibrium solutions found by the simulations trace the well-known S-curve in the density-temperature plane that constitutes the core of the disk thermal-viscous instability model. We confirm that the high values of α ≈ 0.1 occur near the tip of the hot branch of the S-curve, where convection is active. However, we also present thermally stable simulations at lower temperatures that have standard values of α ≈ 0.03 despite the presence of vigorous convection. We find no simple relationship between α and the strength of the convection, as measured by the ratio of convective to radiative flux. The cold branch is only very weakly ionized so, in the second part of this work, we studied the impact of non-ideal MHD effects on transport. Ohmic dissipation is the dominant effect in the conditions of quiescent dwarf novae. We include resistivity in the simulations and find that the MRI-driven transport is quenched (α ≈ 0) below the critical density at which the magnetic Reynolds number Rm ≤ 104. This is problematic because the X-ray emission observed in quiescent systems requires ongoing accretion onto the white dwarf. We verify that these X-rays cannot self-sustain MRI-driven turbulence by photo-ionizing the disk and discuss possible solutions to the issue of accretion in quiescence.

Hot Accretion Spots and Nitrogen Enhancement in Algol-Type Interacting Binary Systems

NASA Astrophysics Data System (ADS)

Peters, Geraldine J.

2013-07-01

The shock from the impact of a gas stream onto the photosphere of a mass gainer in an Algol system is expected to produce a hot spot and also heat circumstellar material that is splashed from the impact site. Furthermore in some cases we expect the stripped-down mass loser (a late-type subgiant) to be nitrogen rich and carbon poor if CNO-processed material is currently being transferred. I will present observational evidence from the Kepler and FUSE spacecrafts for the presence of hot spots and discuss their behavior. FUSE observations of Algols that convincingly show that the gas stream material from some Algol secondaries is N-enhanced and virtually devoid of carbon is also presented. From Kepler data we have identified a long-term phenomenon in which the relative brightness of the quadrature light varies by a few percent and numerically reverses over a time scale of about a 100-400 days. We call the systems T/L (trailing hemisphere/leading hemisphere) variables. Such behavior has never been identified from ground-based photometry. WX Draconis (A8 + K0 IV, P = 1.80 d), a system whose primary displays delta Scuti-like pulsations, is the prototype. The Kepler light curves are being modeled with the latest version of the Wilson-Devinney program that includes the capability of treating migrating hot/cool spots. I will discuss whether the T/L behavior is likely due to a migrating hot accretion spot on the primary or variability in a large cool-spotted area on the secondary. From archival FUSE data we have confirmed the presence of a hot accretion spot in the Algol system U Cephei and present information on the spot parameters/behavior and conditions in a splash plasma from the impact site. Kepler and archival FUSE observations continue to provide important information on the nature of the component stars in Algol systems and the detailed physics of mass transfer, especially the role of accretion hot spots. We are grateful for support from NASA grants NNX11AC78G and NNX12AE44G.

Short-term enteral glutamine does not enhance protein accretion in burned children: a stable isotope study.

PubMed

Sheridan, Robert L; Prelack, Kathrina; Yu, Yong-Ming; Lydon, Martha; Petras, Lisa; Young, Vernon R; Tompkins, Ronald G

2004-06-01

Glutamine is a nonessential amino acid that, in recent years, has been found to play important roles in several metabolic and immunologic processes. It has been theorized that, in a stressed state, it may become "conditionally essential" because the patient's ability to manufacture glutamine may not be adequate to meet their needs under this condition. We chose to evaluate the ability of 48 hours of enteral glutamine to enhance immediate nitrogen accretion in stressed pediatric burn patients. Nine children with serious burns who were tolerating tube feedings were enrolled in a human studies committee-approved protocol in which they received 48 hours of enteral feedings with glutamine replacing 20% of essential and nonessential amino acids and 48 hours of isonitrogenous, isocaloric standard enteral feedings. This interval was chosen to help ensure that the study periods were comparable from a metabolic perspective. At the end of each period, protein kinetics were determined by a primed constant infusion of L-[1-(13)C] leucine tracer. The order of the studies was randomized. Seven children completed both phases of the study. Results were compared by paired t test and are presented as mean +/- standard error of the mean. During the glutamine feeding period, the leucine flux and leucine oxidation rate were significantly lower than those in the conventional feeding period. This reflects a reduction in total leucine intake from 80 +/- 11 to 62 +/- 10 micromol/kg per hour. However, there was no significant difference in the net balance of leucine accretion into proteins between these 2 dietary periods, which indicated that enriched glutamine feeding for 48 hours did not result in an immediate whole body protein gain in this group of pediatric patients. In addition, plasma glutamine concentration showed a moderate increase after 48 hours of supplementation but did not reach significance. Rapid protein accretion does not occur with short-term enteral glutamine supplementation. Several days of glutamine supplementation may be required to restore plasma glutamine levels and stimulate protein synthesis.

Impact of Phosphorus-Based Food Additives on Bone and Mineral Metabolism.

PubMed

Gutiérrez, Orlando M; Luzuriaga-McPherson, Alexandra; Lin, Yiming; Gilbert, Linda C; Ha, Shin-Woo; Beck, George R

2015-11-01

Phosphorus-based food additives can substantially increase total phosphorus intake per day, but the effect of these additives on endocrine factors regulating bone and mineral metabolism is unclear. This study aimed to examine the effect of phosphorus additives on markers of bone and mineral metabolism. Design and Setting, and Participants: This was a feeding study of 10 healthy individuals fed a diet providing ∼1000 mg of phosphorus/d using foods known to be free of phosphorus additives for 1 week (low-additive diet), immediately followed by a diet containing identical food items; however, the foods contained phosphorus additives (additive-enhanced diet). Parallel studies were conducted in animals fed low- (0.2%) and high- (1.8%) phosphorus diets for 5 or 15 weeks. The changes in markers of mineral metabolism after each diet period were measured. Participants were 32 ± 8 years old, 30% male, and 70% black. The measured phosphorus content of the additive-enhanced diet was 606 ± 125 mg higher than the low-additive diet (P < .001). After 1 week of the low-additive diet, consuming the additive-enhanced diet for 1 week significantly increased circulating fibroblast growth factor 23 (FGF23), osteopontin, and osteocalcin concentrations by 23, 10, and 11%, respectively, and decreased mean sclerostin concentrations (P < .05 for all). Similarly, high-phosphorus diets in mice significantly increased blood FGF23, osteopontin and osteocalcin, lowered sclerostin, and decreased bone mineral density (P < .05 for all). The enhanced phosphorus content of processed foods can disturb bone and mineral metabolism in humans. The results of the animal studies suggest that this may compromise bone health.

Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

PubMed

Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

2015-01-01

The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P < .05 was considered statistically significant. A simple (not weighted) kappa statistic was used to assess the agreement between raters. To assess accuracy in identifying bone quality, a chi-square test was used to compare the percent correct for each rater. The benchtop calibration exercise test demonstrated agreement among clinicians (0.75 and 0.92 between raters 1 and 2 and raters 1 and 3, respectively). Raters were more likely to identify the correct bone quality (P > .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may enhance healing within extraction sockets and decrease the healing time prior to dental implant placement.

BMP-non-responsive Sca1+ CD73+ CD44+ mouse bone marrow derived osteoprogenitor cells respond to combination of VEGF and BMP-6 to display enhanced osteoblastic differentiation and ectopic bone formation.

PubMed

Madhu, Vedavathi; Li, Ching-Ju; Dighe, Abhijit S; Balian, Gary; Cui, Quanjun

2014-01-01

Clinical trials on fracture repair have challenged the effectiveness of bone morphogenetic proteins (BMPs) but suggest that delivery of mesenchymal stem cells (MSCs) might be beneficial. It has also been reported that BMPs could not increase mineralization in several MSCs populations, which adds ambiguity to the use of BMPs. However, an exogenous supply of MSCs combined with vascular endothelial growth factor (VEGF) and BMPs is reported to synergistically enhance fracture repair in animal models. To elucidate the mechanism of this synergy, we investigated the osteoblastic differentiation of cloned mouse bone marrow derived MSCs (D1 cells) in vitro in response to human recombinant proteins of VEGF, BMPs (-2, -4, -6, -9) and the combination of VEGF with BMP-6 (most potent BMP). We further investigated ectopic bone formation induced by MSCs pre-conditioned with VEGF, BMP-6 or both. No significant increase in mineralization, phosphorylation of Smads 1/5/8 and expression of the ALP, COL1A1 and osterix genes was observed upon addition of VEGF or BMPs alone to the cells in culture. The lack of CD105, Alk1 and Alk6 expression in D1 cells correlated with poor response to BMPs indicating that a greater care in the selection of MSCs is necessary. Interestingly, the combination of VEGF and BMP-6 significantly increased the expression of ALP, COL1A1 and osterix genes and D1 cells pre-conditioned with VEGF and BMP-6 induced greater bone formation in vivo than the non-conditioned control cells or the cells pre-conditioned with either VEGF or BMP-6 alone. This enhanced bone formation by MSCs correlated with higher CADM1 expression and OPG/RANKL ratio in the implants. Thus, combined action of VEGF and BMP on MSCs enhances osteoblastic differentiation of MSCs and increases their bone forming ability, which cannot be achieved through use of BMPs alone. This strategy can be effectively used for bone repair.

Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model?

PubMed

Walsh, William R; Pelletier, Matthew H; Bertollo, Nicky; Christou, Chris; Tan, Chris

2016-11-01

Polyetheretherketone (PEEK) has a wide range of clinical applications but does not directly bond to bone. Bulk incorporation of osteoconductive materials including hydroxyapatite (HA) into the PEEK matrix is a potential solution to address the formation of a fibrous tissue layer between PEEK and bone and has not been tested. Using in vivo ovine animal models, we asked: (1) Does PEEK-HA improve cortical and cancellous bone ongrowth compared with PEEK? (2) Does PEEK-HA improve bone ongrowth and fusion outcome in a more challenging functional ovine cervical fusion model? The in vivo responses of PEEK-HA Enhanced and PEEK-OPTIMA ® Natural were evaluated for bone ongrowth in the form of dowels implanted in the cancellous and cortical bone of adult sheep and examined at 4 and 12 weeks as well as interbody cervical fusion at 6, 12, and 26 weeks. The bone-implant interface was evaluated with radiographic and histologic endpoints for a qualitative assessment of direct bone contact of an intervening fibrous tissue later. Gamma-irradiated cortical allograft cages were evaluated as well. Incorporating HA into the PEEK matrix resulted in more direct bone apposition as opposed to the fibrous tissue interface with PEEK alone in the bone ongrowth as well as interbody cervical fusions. No adverse reactions were found at the implant-bone interface for either material. Radiography and histology revealed resorption and fracture of the allograft devices in vivo. Incorporating HA into PEEK provides a more favorable environment than PEEK alone for bone ongrowth. Cervical fusion was improved with PEEK-HA compared with PEEK alone as well as allograft bone interbody devices. Improving the bone-implant interface with a PEEK device by incorporating HA may improve interbody fusion results and requires further clinical studies.

Diabetes mellitus related bone metabolism and periodontal disease

PubMed Central

Wu, Ying-Ying; Xiao, E; Graves, Dana T

2015-01-01

Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

Window classification of brain CT images in biomedical articles.

PubMed

Xue, Zhiyun; Antani, Sameer; Long, L Rodney; Demner-Fushman, Dina; Thoma, George R

2012-01-01

Effective capability to search biomedical articles based on visual properties of article images may significantly augment information retrieval in the future. In this paper, we present a new method to classify the window setting types of brain CT images. Windowing is a technique frequently used in the evaluation of CT scans, and is used to enhance contrast for the particular tissue or abnormality type being evaluated. In particular, it provides radiologists with an enhanced view of certain types of cranial abnormalities, such as the skull lesions and bone dysplasia which are usually examined using the " bone window" setting and illustrated in biomedical articles using "bone window images". Due to the inherent large variations of images among articles, it is important that the proposed method is robust. Our algorithm attained 90% accuracy in classifying images as bone window or non-bone window in a 210 image data set.

Quantitative evaluation of bone resorption activity of osteoclast-like cells by measuring calcium phosphate resorbing area using incubator-facilitated and video-enhanced microscopy.

PubMed

Morimoto, Yoshitaka; Hoshino, Hironobu; Sakurai, Takashi; Terakawa, Susumu; Nagano, Akira

2009-04-01

Quantitative evaluation of the ability of bone resorption activity in live osteoclast-like cells (OCLs) has not yet been reported on. In this study, we observed the sequential morphological change of OCLs and measured the resorbing calcium phosphate (CP) area made by OCLs alone and with the addition of elcatonin utilizing incubator facilitated video-enhanced microscopy. OCLs, which were obtained from a coculture of ddy-mouse osteoblastic cells and bone marrow cells, were cultured on CP-coated quartz cover slips. The CP-free area increased constantly in the OCLs alone, whereas it did not increase after the addition of elcatonin. This study showed that analysis of the resorbed areas under the OCL body using this method enables the sequential quantitative evaluation of the bone resorption activity and the effect of several therapeutic agents on bone resorption in vitro.

Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition

USDA-ARS?s Scientific Manuscript database

Glucocorticoids (GCs) have both anabolic and catabolic effects on bone. However, no GC anabolic effect mediator has been identified to date. In this report, we provide the first evidence that glucocorticoid-induced leucine zipper (GILZ), a GC anti-inflammatory effect mediator, can enhance bone forma...

[Project to enhance bone bank tissue storage and distribution procedures].

PubMed

Huang, Jui-Chen; Wu, Chiung-Lan; Chen, Chun-Chuan; Chen, Shu-Hua

2011-10-01

Organ and tissue transplantation are now commonly preformed procedures. Improper organ bank handling procedures may increase infection risks. Execution accuracy in terms of tissue storage and distribution at our bone bank was 80%. We thus proposed an execution improvement project to enhance procedures in order to fulfill the intent of donors and ensure recipient safety. This project was designed to raise nurse professionalism, and ensure patient safety through enhanced tissue storage and distribution procedures. Education programs developed for this project focus on teaching standard operating procedures for bone and ligament storage and distribution, bone bank facility maintenance, trouble shooting and solutions, and periodic inspection systems. Cognition of proper storage and distribution procedures rose from 81% to 100%; Execution accuracy also rose from 80% to 100%. The project successfully conveyed concepts essential to the correct execution of organ storage and distribution procedures and proper organ bank facility management. Achieving and maintaining procedural and management standards is crucial to continued organ donations and the recipient safety.

General-relativistic Simulations of Four States of Accretion onto Millisecond Pulsars

NASA Astrophysics Data System (ADS)

Parfrey, Kyle; Tchekhovskoy, Alexander

2017-12-01

Accreting neutron stars can power a wide range of astrophysical phenomena including short- and long-duration gamma-ray bursts, ultra-luminous X-ray sources, and X-ray binaries. Numerical simulations are a valuable tool for studying the accretion-disk–magnetosphere interaction that is central to these problems, most clearly for the recently discovered transitional millisecond pulsars. However, magnetohydrodynamic (MHD) methods, widely used for simulating accretion, have difficulty in highly magnetized stellar magnetospheres, while force-free methods, suitable for such regions, cannot include the accreting gas. We present an MHD method that can stably evolve essentially force-free, highly magnetized regions, and describe the first time-dependent relativistic simulations of magnetized accretion onto millisecond pulsars. Our axisymmetric general-relativistic MHD simulations for the first time demonstrate how the interaction of a turbulent accretion flow with a pulsar’s electromagnetic wind can lead to the transition of an isolated pulsar to the accreting state. This transition naturally leads to the formation of relativistic jets, whose power can greatly exceed the power of the isolated pulsar’s wind. If the accretion rate is below a critical value, the pulsar instead expels the accretion stream. More generally, our simulations produce for the first time the four possible accretion regimes, in order of decreasing mass accretion rate: (a) crushed magnetosphere and direct accretion; (b) magnetically channeled accretion onto the stellar poles; (c) the propeller state, where material enters through the light cylinder but is prevented from accreting by the centrifugal barrier; (d) almost perfect exclusion of the accretion flow from the light cylinder by the pulsar wind.

Mitigating HZE Radiation-Induced Deficits in Marrow-Derived Mesenchymal Progenitor Cells and Skeletal Structure

NASA Technical Reports Server (NTRS)

Globus, Ruth K.; Schreurs, Ann-Sofie; Shirazi-Fard, Yasaman; Terada, Masahiro; Alwood, Joshua; Halloran, Bernard; Tahimic, Candice

2016-01-01

Future long-duration space exploration beyond the earths magnetosphere will increase human exposure to space radiation and associated risks to skeletal health. We hypothesize that oxidative stress resulting from radiation exposure causes progressive bone loss and dysfunction in associated tissue. In animal studies, increased free radical formation is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility.

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

PubMed

Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

2015-01-01

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.

Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.

PubMed

Farman, H H; Windahl, S H; Westberg, L; Isaksson, H; Egecioglu, E; Schele, E; Ryberg, H; Jansson, J O; Tuukkanen, J; Koskela, A; Xie, S K; Hahner, L; Zehr, J; Clegg, D J; Lagerquist, M K; Ohlsson, C

2016-08-01

Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)α. Central ERα exerts an inhibitory role on bone mass. ERα is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERα in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERα expression specifically in POMC neurons (POMC-ERα(-/-)). Female POMC-ERα(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 μg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERα(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 ± 34%, P < .01) and mechanical strength (+193 ± 38%, P < .01). To test whether ERα in VMN is involved in the regulation of bone mass, ERα was silenced using an adeno-associated viral vector. Silencing of ERα in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERα in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERα activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERα-mediated effects in bone determines cortical bone mass in female mice.

The intensity of physical activity influences bone mineral accrual in childhood: the childhood health, activity and motor performance school (the CHAMPS) study, Denmark

PubMed Central

2013-01-01

Background Studies indicate genetic and lifestyle factors can contribute to optimal bone development. In particular, the intensity level of physical activity may have an impact on bone health. This study aims to assess the relationship between physical activity at different intensities and Bone Mineral Content (BMC), Bone Mineral Density (BMD) and Bone Area (BA) accretion. Methods This longitudinal study is a part of The CHAMPS study-DK. Whole-body DXA scans were performed at baseline and after two years follows up. BMC, BMD, and BA were measured. The total body less head (TBLH) values were used. Physical activity (PA) was recorded by accelerometers (ActiGraph, model GT3X). Percentages of different PA intensity levels were calculated and log odds of two intensity levels of activity relative to the third level were calculated. Multilevel regression analyses were used to assess the relationship between the categories of physical activity and bone traits. Results Of 800 invited children, 742 (93%) accepted to participate. Of these, 682/742 (92%) participated at follow up. Complete datasets were obtained in 602/742 (81%) children. Mean (range) of age was 11.5 years (9.7-13.9). PA at different intensity levels was for boys and girls respectively, sedentary 62% and 64%, low 29% for both genders and moderate to high 9% and 7% of the total time. Mean (range) BMC, BMD, and BA was 1179 g (563–2326), 0.84 g/cm2 (0.64-1.15) and 1393 cm2 (851–2164), respectively. Valid accelerometer data were obtained for a mean of 6.1 days, 13 hours per day. Conclusions There 7was a positive relationship between the log odds of moderate to high-level PA versus low level activity and BMC, BMD and BA. Children with an increased proportion of time in moderate to high-level activity as opposed to sedentary and low-level activity achieved positive effects on BMC, BMD and BA. PMID:23452342

Heparanase promotes myeloma progression by inducing mesenchymal features and motility of myeloma cells.

PubMed

Li, Juan; Pan, Qianying; Rowan, Patrick D; Trotter, Timothy N; Peker, Deniz; Regal, Kellie M; Javed, Amjad; Suva, Larry J; Yang, Yang

2016-03-08

Bone dissemination and bone disease occur in approximately 80% of patients with multiple myeloma (MM) and are a major cause of patient mortality. We previously demonstrated that MM cell-derived heparanase (HPSE) is a major driver of MM dissemination to and progression in new bone sites. However the mechanism(s) by which HPSE promotes MM progression remains unclear. In the present study, we investigated the involvement of mesenchymal features in HPSE-promoted MM progression in bone. Using a combination of molecular, biochemical, cellular, and in vivo approaches, we demonstrated that (1) HPSE enhanced the expression of mesenchymal markers in both MM and vascular endothelial cells; (2) HPSE expression in patient myeloma cells positively correlated with the expression of the mesenchymal markers vimentin and fibronectin. Additional mechanistic studies revealed that the enhanced mesenchymal-like phenotype induced by HPSE in MM cells is due, at least in part, to the stimulation of the ERK signaling pathway. Finally, knockdown of vimentin in HPSE expressing MM cells resulted in significantly attenuated MM cell dissemination and tumor growth in vivo. Collectively, these data demonstrate that the mesenchymal features induced by HPSE in MM cells contribute to enhanced tumor cell motility and bone-dissemination.

Dietary Pseudopurpurin Improves Bone Geometry Architecture and Metabolism in Red-Bone Guishan Goats

PubMed Central

Han, TieSuo; Li, Peng; Wang, JianGuo; Liu, GuoWen; Wang, Zhe; Ge, ChangRong; Gao, ShiZheng

2012-01-01

Red-colored bones were found initially in some Guishan goats in the 1980s, and they were designated red-boned goats. However, it is not understood what causes the red color in the bone, or whether the red material changes the bone geometry, architecture, and metabolism of red-boned goats. Pseudopurpurin was identified in the red-colored material of the bone in red-boned goats by high-performance liquid chromatography–electrospray ionization–mass spetrometry and nuclear magnetic resonance analysis. Pseudopurpurin is one of the main constituents of Rubia cordifolia L, which is eaten by the goats. The assessment of the mechanical properties and micro-computed tomography showed that the red-boned goats displayed an increase in the trabecular volume fraction, trabecular thickness, and the number of trabeculae in the distal femur. The mean thickness, inner perimeter, outer perimeter, and area of the femoral diaphysis were also increased. In addition, the trabecular separation and structure model index of the distal femur were decreased, but the bone mineral density of the whole femur and the mechanical properties of the femoral diaphysis were enhanced in the red-boned goats. Meanwhile, expression of alkaline phosphatase and osteocalcin mRNA was higher, and the ratio of the receptor activator of the nuclear factor kappa B ligand to osteoprotegerin was markedly lower in the bone marrow of the red-boned goats compared with common goats. To confirm further the effect of pseudopurpurin on bone geometry, architecture, and metabolism, Wistar rats were fed diets to which pseudopurpurin was added for 5 months. Similar changes were observed in the femurs of the treated rats. The above results demonstrate that pseudopurpurin has a close affinity with the mineral salts of bone, and consequently a high level of mineral salts in the bone cause an improvement in bone strength and an enhancement in the structure and metabolic functions of the bone. PMID:22624037

Biomimetics of Bone Implants: The Regenerative Road.

PubMed

Brett, Elizabeth; Flacco, John; Blackshear, Charles; Longaker, Michael T; Wan, Derrick C

2017-01-01

The current strategies for healing bone defects are numerous and varied. At the core of each bone healing therapy is a biomimetic mechanism, which works to enhance bone growth. These range from porous scaffolds, bone mineral usage, collagen, and glycosaminoglycan substitutes to transplanted cell populations. Bone defects face a range of difficulty in their healing, given the composite of dense outer compact bone and blood-rich inner trabecular bone. As such, the tissue possesses a number of inherent characteristics, which may be clinically harnessed as promoters of bone healing. These include mechanical characteristics, mineral composition, native collagen content, and cellular fraction of bone. This review charts multiple biomimetic strategies to help heal bony defects in large and small osseous injury sites, with a special focus on cell transplantation.

Bone Growth, Mechanical Stimulus and IGF-1

DTIC Science & Technology

2006-10-01

suffer a bone fracture by the time they reach skeletal maturity. While strenuous physical activity and occupational hazards are key factors in the...females with low bone density. Ultimately, this information could be of great benefit to enhance musculoskeletal development and decrease the risk ...pathogenesis of these fractures , several studies indicate that teenagers who sustain fractures also have decreased bone mass. Therefore, the use of low

High-fat diet enhances and plasminogen activator inhibitor-1 deficiency attenuates bone loss in mice with Lewis Lung carcinoma

USDA-ARS?s Scientific Manuscript database

This study determined the effects of a high-fat diet and plasminogen activator inhibitor-1 deficiency (PAI-1-/-) on bone structure in mice bearing Lewis lung carcinoma (LLC) in lungs. Reduction in bone volume fraction (BV/TV) by 22% and 21%, trabecular number (Tb.N) by 8% and 4% and bone mineral de...

Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

NASA Astrophysics Data System (ADS)

Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

2017-08-01

Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the rehabilitation of disused or aged osteoporosis.

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

PubMed Central

Dennis, S. Connor; Berkland, Cory J.; Bonewald, Lynda F.

2015-01-01

Autologous bone grafting (ABG) remains entrenched as the gold standard of treatment in bone regenerative surgery. Consequently, many marginally successful bone tissue engineering strategies have focused on mimicking portions of ABG's “ideal” osteoconductive, osteoinductive, and osteogenic composition resembling the late reparative stage extracellular matrix (ECM) in bone fracture repair, also known as the “hard” or “bony” callus. An alternative, less common approach that has emerged in the last decade harnesses endochondral (EC) ossification through developmental engineering principles, which acknowledges that the molecular and cellular mechanisms involved in developmental skeletogenesis, specifically EC ossification, are closely paralleled during native bone healing. EC ossification naturally occurs during the majority of bone fractures and, thus, can potentially be utilized to enhance bone regeneration for nearly any orthopedic indication, especially in avascular critical-sized defects where hypoxic conditions favor initial chondrogenesis instead of direct intramembranous ossification. The body's native EC ossification response, however, is not capable of regenerating critical-sized defects without intervention. We propose that an underexplored potential exists to regenerate bone through the native EC ossification response by utilizing strategies which mimic the initial inflammatory or fibrocartilaginous ECM (i.e., “pro-” or “soft” callus) observed in the early reparative stage of bone fracture repair. To date, the majority of strategies utilizing this approach rely on clinically burdensome in vitro cell expansion protocols. This review will focus on the confluence of two evolving areas, (1) native ECM biomaterials and (2) developmental engineering, which will attempt to overcome the technical, business, and regulatory challenges that persist in the area of bone regeneration. Significant attention will be given to native “raw” materials and ECM-based designs that provide necessary osteo- and chondro-conductive and inductive features for enhancing EC ossification. In addition, critical perspectives on existing stem cell-based therapeutic strategies will be discussed with a focus on their use as an extension of the acellular ECM-based designs for specific clinical indications. Within this framework, a novel realm of unexplored design strategies for bone tissue engineering will be introduced into the collective consciousness of the regenerative medicine field. PMID:25336144

MRI evaluation of infectious and non-infectious synovitis: preliminary studies in a rabbit model.

PubMed

Strouse, P J; Londy, F; DiPietro, M A; Teo, E L; Chrisp, C E; Doi, K

1999-05-01

Literature on magnetic resonance imaging (MR) evaluation of inflammatory joint effusions is sparse. To describe an animal model for studying infectious and non-infectious joint effusions with magnetic resonance imaging. Ten rabbit knees with septic arthritis and four with talc synovitis were imaged with MR. Contralateral knees injected with saline served as controls. Fat saturation T2-weighted and gadolinium-enhanced T1-weighted images were assessed for joint effusion, and periarticular and adjacent intraosseous increased signal or enhancement. Each knee was cultured and underwent pathologic examination. Both Staphylococcus aureus and talc produced effusions in all knees. The degree of periarticular signal and enhancement was greater in infected knees than talc-injected knees. No abnormal enhancement was seen within bone. Pathologic examination showed a greater degree of inflammation and joint destruction in the infected knees, but no evidence of osteomyelitis. A greater degree of abnormal signal and enhancement seen on MR suggests a more vigorous inflammatory process, as seen with septic arthritis. In spite of advanced septic arthritis, no enhancement was evident within bone, suggesting that enhancement within bone is not an expected finding in isolated septic arthritis and should raise concern for osteomyelitis.

Recent biological trends in management of fracture non-union

PubMed Central

Emara, Khaled M; Diab, Ramy Ahmed; Emara, Ahmed Khaled

2015-01-01

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. Currently, there is a plethora of different strategies to augment the impaired or “insufficient” bone-regeneration process, including the “gold standard” autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved “local” strategies in terms of tissue engineering and gene therapy, or even “systemic” enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. PMID:26396938

Hot-boning enhances cook yield of boneless skinless chicken thighs

USDA-ARS?s Scientific Manuscript database

Three experiments were conducted to evaluate effects of postmortem deboning time on cook yield of boneless skinless chicken thighs. In Experiment 1 (3 replications), chicken thigh meat was separated from bones at 0.45 (hot-bone), 2, and 24 h and trimmed to obtain iliotibialis muscle. The iliotibiali...

An Optical/Near-infrared Investigation of HD 100546 b with the Gemini Planet Imager and MagAO

NASA Astrophysics Data System (ADS)

Rameau, Julien; Follette, Katherine B.; Pueyo, Laurent; Marois, Christian; Macintosh, Bruce; Millar-Blanchaer, Maxwell; Wang, Jason J.; Vega, David; Doyon, René; Lafrenière, David; Nielsen, Eric L.; Bailey, Vanessa; Chilcote, Jeffrey K.; Close, Laird M.; Esposito, Thomas M.; Males, Jared R.; Metchev, Stanimir; Morzinski, Katie M.; Ruffio, Jean-Baptiste; Wolff, Schuyler G.; Ammons, S. M.; Barman, Travis S.; Bulger, Joanna; Cotten, Tara; De Rosa, Robert J.; Duchene, Gaspard; Fitzgerald, Michael P.; Goodsell, Stephen; Graham, James R.; Greenbaum, Alexandra Z.; Hibon, Pascale; Hung, Li-Wei; Ingraham, Patrick; Kalas, Paul; Konopacky, Quinn; Larkin, James E.; Maire, Jérôme; Marchis, Franck; Oppenheimer, Rebecca; Palmer, David; Patience, Jennifer; Perrin, Marshall D.; Poyneer, Lisa; Rajan, Abhijith; Rantakyrö, Fredrik T.; Marley, Mark S.; Savransky, Dmitry; Schneider, Adam C.; Sivaramakrishnan, Anand; Song, Inseok; Soummer, Remi; Thomas, Sandrine; Wallace, J. Kent; Ward-Duong, Kimberly; Wiktorowicz, Sloane

2017-06-01

We present H band spectroscopic and Hα photometric observations of HD 100546 obtained with the Gemini Planet Imager and the Magellan Visible AO camera. We detect H band emission at the location of the protoplanet HD 100546 b, but show that the choice of data processing parameters strongly affects the morphology of this source. It appears point-like in some aggressive reductions, but rejoins an extended disk structure in the majority of the others. Furthermore, we demonstrate that this emission appears stationary on a timescale of 4.6 years, inconsistent at the 2σ level with a Keplerian clockwise orbit at 59 au in the disk plane. The H band spectrum of the emission is inconsistent with any type of low effective temperature object or accreting protoplanetary disk. It strongly suggests a scattered-light origin, as this is consistent with the spectrum of the star and the spectra extracted at other locations in the disk. A non-detection at the 5σ level of HD 100546 b in differential Hα imaging places an upper limit, assuming the protoplanet lies in a gap free of extinction, on the accretion luminosity of 1.7 × 10-4 L ⊙ and M\\dot{M}< 6.3× {10}-7 {M}{Jup}2 {{yr}}-1 for 1 R Jup. These limits are comparable to the accretion luminosity and accretion rate of T-Tauri stars or LkCa 15 b. Taken together, these lines of evidence suggest that the H band source at the location of HD 100546 b is not emitted by a planetary photosphere or an accreting circumplanetary disk but is a disk feature enhanced by the point-spread function subtraction process. This non-detection is consistent with the non-detection in the K band reported in an earlier study but does not exclude the possibility that HD 100546 b is deeply embedded.

Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by affecting both osteoblastogenesis and osteoclastogenesis

PubMed Central

Su, Nan; Sun, Qidi; Li, Can; Lu, Xiumin; Qi, Huabing; Chen, Siyu; Yang, Jing; Du, Xiaolan; Zhao, Ling; He, Qifen; Jin, Min; Shen, Yue; Chen, Di; Chen, Lin

2010-01-01

Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on bone formation and bone remodeling at adult stages of ACH have not been fully investigated. Using micro-computed tomography and histomorphometric analyses, we found that 2-month-old Fgfr3G369C/+ mice (mouse model mimicking human ACH) showed decreased bone mass due to reduced trabecular bone volume and bone mineral density, defect in bone mineralization and increased osteoclast numbers and activity. Compared with primary cultures of bone marrow stromal cells (BMSCs) from wild-type mice, Fgfr3G369C/+ cultures showed decreased cell proliferation, increased osteogenic differentiation including up-regulation of alkaline phosphatase activity and expressions of osteoblast marker genes, and reduced bone matrix mineralization. Furthermore, our studies also suggest that decreased cell proliferation and enhanced osteogenic differentiation observed in Fgfr3G369C/+ BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2 activity is responsible for the impaired bone matrix mineralization. In addition, in vitro osteoclast formation and bone resorption assays demonstrated that osteoclast numbers and bone resorption area were increased in cultured bone marrow cells derived from Fgfr3G369C/+ mice. These findings demonstrate that gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating both osteoblast and osteoclast activities. Our studies provide new insight into the mechanism underlying the development of ACH. PMID:20053668

Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

PubMed

Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

2014-01-01

In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

Delivery of Bioactive Lipids from Composite Microgel-Microsphere Injectable Scaffolds Enhances Stem Cell Recruitment and Skeletal Repair

PubMed Central

Das, Anusuya; Barker, Daniel A.; Wang, Tiffany; Lau, Cheryl M.; Lin, Yong; Botchwey, Edward A.

2014-01-01

In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy. PMID:25077607

Differences in responses to X-ray exposure between osteoclast and osteoblast cells

PubMed Central

Zhang, Jian; Wang, Ziyang; Wu, Anqing; Nie, Jing; Pei, Hailong; Hu, Wentao; Wang, Bing; Shang, Peng; Li, Bingyan

2017-01-01

Abstract Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss. PMID:28541506

NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation

PubMed Central

Chang, Jia; Liu, Fei; Lee, Min; Wu, Benjamin; Ting, Kang; Zara, Janette N.; Soo, Chia; Al Hezaimi, Khalid; Zou, Weiping; Chen, Xiaohong; Mooney, David J.; Wang, Cun-Yu

2013-01-01

Mesenchymal stem cell (MSC)-based transplantation is a promising therapeutic approach for bone regeneration and repair. In the realm of therapeutic bone regeneration, the defect or injured tissues are frequently inflamed with an abnormal expression of inflammatory mediators. Growing evidence suggests that proinflammatory cytokines inhibit osteogenic differentiation and bone formation. Thus, for successful MSC-mediated repair, it is important to overcome the inflammation-mediated inhibition of tissue regeneration. In this study, using genetic and chemical approaches, we found that proinflammatory cytokines TNF and IL-17 stimulated IκB kinase (IKK)–NF-κB and impaired osteogenic differentiation of MSCs. In contrast, the inhibition of IKK–NF-κB significantly enhanced MSC-mediated bone formation. Mechanistically, we found that IKK–NF-κB activation promoted β-catenin ubiquitination and degradation through induction of Smurf1 and Smurf2. To translate our basic findings to potential clinic applications, we showed that the IKK small molecule inhibitor, IKKVI, enhanced osteogenic differentiation of MSCs. More importantly, the delivery of IKKVI promoted MSC-mediated craniofacial bone regeneration and repair in vivo. Considering the well established role of NF-κB in inflammation and infection, our results suggest that targeting IKK–NF-κB may have dual benefits in enhancing bone regeneration and repair and inhibiting inflammation, and this concept may also have applicability in many other tissue regeneration situations. PMID:23690607

Strontium ranelate: a novel mode of action leading to renewed bone quality.

PubMed

Ammann, Patrick

2005-01-01

Various bone resorption inhibitors and bone stimulators have been shown to decrease the risk of osteoporotic fractures. However, there is still a need for agents promoting bone formation by inducing positive uncoupling between bone formation and bone resorption. In vitro studies have suggested that strontium ranelate enhances osteoblast cell replication and activity. Simultaneously, strontium ranelate dose-dependently inhibits osteoclast activity. In vivo studies indicate that strontium ranelate stimulates bone formation and inhibits bone resorption and prevents bone loss and/or promotes bone gain. This positive uncoupling between bone formation and bone resorption results in bone gain and improvement in bone geometry and microarchitecture, without affecting the intrinsic bone tissue quality. Thus, all the determinants of bone strength are positively influenced. In conclusion, strontium ranelate, a new treatment of postmenopausal osteoporosis, acts through an innovative mode of action, both stimulating bone formation and inhibiting bone resorption, resulting in the rebalancing of bone turnover in favor of bone formation. Strontium ranelate increases bone mass while preserving the bone mineralization process, resulting in improvement in bone strength and bone quality.

In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation.

PubMed

Kettenberger, Ulrike; Luginbuehl, Vera; Procter, Philip; Pioletti, Dominique P

2017-07-01

Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells.

PubMed

Chen, Ching-Yun; Tseng, Kuo-Yun; Lai, Yen-Liang; Chen, Yo-Shen; Lin, Feng-Huei; Lin, Shankung

2017-01-01

Many studies have indicated that loss of the osteoblastogenic potential in bone marrow mesenchymal stem cells (bmMSCs) is the major component in the etiology of the aging-related bone deficit. But how the bmMSCs lose osteogenic capability in aging is unclear. Using 2-dimentional cultures, we examined the dose response of human bmMSCs, isolated from adult and aged donors, to exogenous insulin-like growth factor 1 (IGF-1), a growth factor regulating bone formation. The data showed that the mitogenic activity and the osteoblastogenic potential of bmMSCs in response to IGF-1 were impaired with aging, whereas higher doses of IGF-1 increased the proliferation rate and osteogenic potential of aging bmMSCs. Subsequently, we seeded IGF-1-overexpressing aging bmMSCs into calcium-alginate scaffolds and incubated in a bioreactor with constant perfusion for varying time periods to examine the effect of IGF-1 overexpression to the bone-forming capability of aging bmMSCs. We found that IGF-1 overexpression in aging bmMSCs facilitated the formation of cell clusters in scaffolds, increased the cell survival inside the cell clusters, induced the expression of osteoblast markers, and enhanced the biomineralization of cell clusters. These results indicated that IGF-1 overexpression enhanced cells' osteogenic capability. Thus, our data suggest that the aging-related loss of osteogenic potential in bmMSCs can be attributed in part to the impairment in bmMSCs' IGF-1 signaling, and support possible application of IGF-1-overexpressing autologous bmMSCs in repairing bone defect of the elderly and in producing bone graft materials for repairing large scale bone injury in the elderly.

Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.

PubMed

Hildreth, Blake Eason; Williams, Michelle M; Dembek, Katarzyna A; Hernon, Krista M; Rosol, Thomas J; Toribio, Ramiro E

2015-12-01

Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.

BMP-2 Derived Peptide and Dexamethasone Incorporated Mesoporous Silica Nanoparticles for Enhanced Osteogenic Differentiation of Bone Mesenchymal Stem Cells.

PubMed

Zhou, Xiaojun; Feng, Wei; Qiu, Kexin; Chen, Liang; Wang, Weizhong; Nie, Wei; Mo, Xiumei; He, Chuanglong

2015-07-29

Bone morphogenetic protein-2 (BMP-2), a growth factor that induces osteoblast differentiation and promotes bone regeneration, has been extensively investigated in bone tissue engineering. The peptides of bioactive domains, corresponding to residues 73-92 of BMP-2 become an alternative to reduce adverse side effects caused by the use of high doses of BMP-2 protein. In this study, BMP-2 peptide functionalized mesoporous silica nanoparticles (MSNs-pep) were synthesized by covalently grafting BMP-2 peptide on the surface of nanoparticles via an aminosilane linker, and dexamethasone (DEX) was then loaded into the channel of MSNs to construct nanoparticulate osteogenic delivery systems (DEX@MSNs-pep). The in vitro cell viability of MSNs-pep was tested with bone mesenchymal stem cells (BMSCs) exposure to different particle concentrations, revealing that the functionalized MSNs had better cytocompatibility than their bare counterparts, and the cellular uptake efficiency of MSNs-pep was remarkably larger than that of bare MSNs. The in vitro results also show that the MSNs-pep promoted osteogenic differentiation of BMSCs in terms of the levels of alkaline phosphatase (ALP) activity, calcium deposition, and expression of bone-related protein. Moreover, the osteogenic differentiation of BMSCs can be further enhanced by incorporating of DEX into MSNs-pep. After intramuscular implantation in rats for 3 weeks, the computed tomography (CT) images and histological examination indicate that this nanoparticulate osteogenic delivery system induces effective osteoblast differentiation and bone regeneration in vivo. Collectively, the BMP-2 peptide and DEX incorporated MSNs can act synergistically to enhance osteogenic differentiation of BMSCs, which have potential applications in bone tissue engineering.

Sphingosine 1-Phosphate- and C-C Chemokine Receptor 2-Dependent Activation of CD4+ Plasmacytoid Dendritic Cells in the Bone Marrow Contributes to Signs of Sepsis-Induced Immunosuppression

PubMed Central

Smirnov, Anna; Pohlmann, Stephanie; Nehring, Melanie; Ali, Shafaqat; Mann-Nüttel, Ritu; Scheu, Stefanie; Antoni, Anne-Charlotte; Hansen, Wiebke; Büettner, Manuela; Gardiasch, Miriam J.; Westendorf, Astrid M.; Wirsdörfer, Florian; Pastille, Eva; Dudda, Marcel; Flohé, Stefanie B.

2017-01-01

Sepsis is the dysregulated response of the host to systemic, mostly bacterial infection, and is associated with an enhanced susceptibility to life-threatening opportunistic infections. During polymicrobial sepsis, dendritic cells (DCs) secrete enhanced levels of interleukin (IL) 10 due to an altered differentiation in the bone marrow and contribute to the development of immunosuppression. We investigated the origin of the altered DC differentiation using murine cecal ligation and puncture (CLP), a model for human polymicrobial sepsis. Bone marrow cells (BMC) were isolated after sham or CLP operation, the cellular composition was analyzed, and bone marrow-derived DCs (BMDCs) were generated in vitro. From 24 h on after CLP, BMC gave rise to BMDC that released enhanced levels of IL-10. In parallel, a population of CD11chiMHCII+CD4+ DCs expanded in the bone marrow in a MyD88-dependent manner. Prior depletion of the CD11chiMHCII+CD4+ DCs from BMC in vitro reversed the increased IL-10 secretion of subsequently differentiating BMDC. The expansion of the CD11chiMHCII+CD4+ DC population in the bone marrow after CLP required the function of sphingosine 1-phosphate receptors and C-C chemokine receptor (CCR) 2, the receptor for C-C chemokine ligand (CCL) 2, but was not associated with monocyte mobilization. CD11chiMHCII+CD4+ DCs were identified as plasmacytoid DCs (pDCs) that had acquired an activated phenotype according to their increased expression of MHC class II and CD86. A redistribution of CD4+ pDCs from MHC class II− to MHC class II+ cells concomitant with enhanced expression of CD11c finally led to the rise in the number of CD11chiMHCII+CD4+ DCs. Enhanced levels of CCL2 were found in the bone marrow of septic mice and the inhibition of CCR2 dampened the expression of CD86 on CD4+ pDCs after CLP in vitro. Depletion of pDCs reversed the bias of splenic DCs toward increased IL-10 synthesis after CLP in vivo. Thus, during polymicrobial sepsis, CD4+ pDCs are activated in the bone marrow and induce functional reprogramming of differentiating BMDC toward an immunosuppressive phenotype. PMID:29218051

On the efficiency of jet production in FR II radio galaxies and quasars

NASA Astrophysics Data System (ADS)

Rusinek, Katarzyna; Sikora, Marek; Kozieł-Wierzbowska, Dorota; Godfrey, Leith

2017-04-01

Jet powers in many radio galaxies with extended radio structures appear to exceed their associated accretion luminosities. In systems with very low accretion rates, this is likely due to the very low accretion luminosities resulting from radiatively inefficient accretion flows. In systems with high accretion rates, the accretion flows are expected to be radiatively efficient, and the production of such powerful jets may require an accretion scenario, which involves magnetically arrested discs (MADs). However, numerical simulations of the MAD scenario indicate that jet production efficiency is large only for geometrically thick accretion flows and scales roughly with (H/R)2, where H is the disc height and R is the distance from the black hole. Using samples of FR II radio galaxies and quasars accreting at moderate accretion rates, we show that their jets are much more powerful than predicted by the MAD scenario. We discuss possible origins of this discrepancy, suggesting that it can be related to approximations adopted in magnetohydrodynamic simulations to treat optically thick accretion flow within the MAD zone, or may indicate that accretion discs are geometrically thicker than the standard theory predicts.

Massive star formation by accretion. I. Disc accretion

NASA Astrophysics Data System (ADS)

Haemmerlé, L.; Eggenberger, P.; Meynet, G.; Maeder, A.; Charbonnel, C.

2016-01-01

Context. Massive stars likely form by accretion and the evolutionary track of an accreting forming star corresponds to what is called the birthline in the Hertzsprung-Russell (HR) diagram. The shape of this birthline is quite sensitive to the evolution of the entropy in the accreting star. Aims: We first study the reasons why some birthlines published in past years present different behaviours for a given accretion rate. We then revisit the question of the accretion rate, which allows us to understand the distribution of the observed pre-main-sequence (pre-MS) stars in the HR diagram. Finally, we identify the conditions needed to obtain a large inflation of the star along its pre-MS evolution that may push the birthline towards the Hayashi line in the upper part of the HR diagram. Methods: We present new pre-MS models including accretion at various rates and for different initial structures of the accreting core. We compare them with previously published equivalent models. From the observed upper envelope of pre-MS stars in the HR diagram, we deduce the accretion law that best matches the accretion history of most of the intermediate-mass stars. Results: In the numerical computation of the time derivative of the entropy, some treatment leads to an artificial loss of entropy and thus reduces the inflation that the accreting star undergoes along the birthline. In the case of cold disc accretion, the existence of a significant swelling during the accretion phase, which leads to radii ≳ 100 R⊙ and brings the star back to the red part of the HR diagram, depends sensitively on the initial conditions. For an accretion rate of 10-3M⊙ yr-1, only models starting from a core with a significant radiative region evolve back to the red part of the HR diagram. We also obtain that, in order to reproduce the observed upper envelope of pre-MS stars in the HR diagram with an accretion law deduced from the observed mass outflows in ultra-compact HII regions, the fraction of the mass that is accreted onto the star should represent a decreasing fraction of the mass outflows when the mass of the accreting object increases. In other words, the accretion efficiency (mass effectively accreted onto the star with respect to the total in falling matter) decreases when the mass of the star increases.

Analysis of relevant proteins from bone graft harvested using the reamer irrigator and aspirator system (RIA) versus iliac crest (IC) bone graft and RIA waste water.

PubMed

Crist, Brett D; Stoker, Aaron M; Stannard, James P; Cook, James L

2016-08-01

Femoral reaming using a Reamer Irrigator Aspirator (RIA) can produce greater than three liters of waste water per procedure, which contains cells and proteins that could promote bone healing. This purpose of this study was to determine the protein profile of RIA waste water and compare protein synthesis by cells harvested via RIA versus iliac crest (IC) bone graft. Bone graft was collected from 30 patients-15 using RIA from the femur and 15 harvested from the iliac crest. Waste water collected during the RIA procedure was analyzed in 12 patients. Cells from each graft were cultured in monolayer using growth media for 14days and inductive media for the next 14days. Media samples were collected on days 14, 21, and 28. Proteins for analysis were chosen based on their potential in bone healing, pro-inflammatory, and anti-inflammatory processes. Proteins present in RIA waste water indicate the potential for clinical use of this filtrate as an adjunct for enhancing bone production, healing, and remodeling. Similarly, cells cultured from RIA bone graft harvests compared favorably to those from iliac crest bone grafts with respect to their potential to aid in bone healing. RIA waste water has potential to serve as an autogenic and allogenic enhancer for bone healing. Continued development of processing protocols for viable commercial use of the waste water and pre-clinical studies designed to evaluate RIA waste water products for bone healing are ongoing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Repeated Transient Jets from a Warped Disk in the Symbiotic Prototype Z And: A Link to the Long-lasting Active Phase

NASA Astrophysics Data System (ADS)

Skopal, Augustin; Tarasova, Taya. N.; Wolf, Marek; Dubovský, Pavol A.; Kudzej, Igor

2018-05-01

Active phases of some symbiotic binaries survive for a long time, from years to decades. The accretion process onto a white dwarf (WD) sustaining long-lasting activity, and sometimes leading to collimated ejection, is not well understood. We present the repeated emergence of highly collimated outflows (jets) from the symbiotic prototype Z And during its 2008 and 2009–10 outbursts and suggest their link to the current long-lasting (from 2000) active phase. We monitored Z And with high-resolution spectroscopy, multicolor UBVR C—and high time resolution—photometry. The well-pronounced bipolar jets were ejected again during the 2009–10 outburst together with the simultaneous emergence of the rapid photometric variability (Δm ≈ 0.06 mag) on the timescale of hours, showing similar properties as those during the 2006 outburst. These phenomena and the measured disk–jets connection could be caused by the radiation-induced warping of the inner disk due to a significant increase of the burning WD luminosity. Ejection of transient jets by Z And around outburst maxima signals a transient accretion at rates above the upper limit of the stable hydrogen burning on the WD surface, and thus proves the nature of Z And-type outbursts. The enhanced accretion through the disk warping, supplemented by the accretion from the giant’s wind, can keep a high luminosity of the WD for a long time, until depletion of the disk. In this way, the jets provide a link to long-lasting active phases of Z And.

The Evolution of Massive Close Binaries: Anomalous Relationship between Nitrogen Abundances and Rotational Velocities

NASA Astrophysics Data System (ADS)

Song, Hanfeng; Wang, Jiangtao; Song, Fen; Zhang, Ruiyu; Li, Zhi; Peng, Weiguo; Zhan, Qiong; Jing, Jianghong

2018-05-01

The combined effects of rotation and mass accretion on the evolution of binary systems are investigated in this work. Rotational binaries provide us with a promising channel that could explain the abnormal phenomenon of the nitrogen abundances in Groups 1 and 2 of the Galactic Hunter diagram. Group 1 contains fast-rotating but nitrogen-unenriched stars, whereas Group 2 includes apparently slowly rotating but nitrogen-enhanced stars. The donor star suffers from heavy mass loss that progressively exposes deep layers of nitrogen and corresponding angular momentum loss that can efficiently spin the star down. Rapid-rotation stars without nitrogen enrichment may be related to mass gainers that had accreted little matter from a close companion and then been spun up to rapid rotation. Nitrogen enrichment of mass gainers can be greatly suppressed by low accreting efficiency, which is induced by critical rotation, thermohaline mixing, and the gradient of mean molecular weight. Nitrogen enrichment due to mass accretion appears to be more efficient than that due to rotational mixing, because there exist thermohaline instabilities during Roche lobe overflow. The mixing in the enlarged convective core reduces carbon and nitrogen abundances but increases oxygen abundances in mass gainers. This process significantly triggers CNO cycling but does not support CN cycling. The orbital separation can be widened because of the nonconservative mass transfer, and this process gives rise to weak tidal torques. Therefore, invoking binaries has the potential to simultaneously explain the observed stars in Groups 1 and 2 of the Galactic Hunter diagram.

Medial tibial pain: a dynamic contrast-enhanced MRI study.

PubMed

Mattila, K T; Komu, M E; Dahlström, S; Koskinen, S K; Heikkilä, J

1999-09-01

The purpose of this study was to compare the sensitivity of different magnetic resonance imaging (MRI) sequences to depict periosteal edema in patients with medial tibial pain. Additionally, we evaluated the ability of dynamic contrast-enhanced imaging (DCES) to depict possible temporal alterations in muscular perfusion within compartments of the leg. Fifteen patients with medial tibial pain were examined with MRI. T1-, T2-weighted, proton density axial images and dynamic and static phase post-contrast images were compared in ability to depict periosteal edema. STIR was used in seven cases to depict bone marrow edema. Images were analyzed to detect signs of compartment edema. Region-of-interest measurements in compartments were performed during DCES and compared with controls. In detecting periosteal edema, post-contrast T1-weighted images were better than spin echo T2-weighted and proton density images or STIR images, but STIR depicted the bone marrow edema best. DCES best demonstrated the gradually enhancing periostitis. Four subjects with severe periosteal edema had visually detectable pathologic enhancement during DCES in the deep posterior compartment of the leg. Percentage enhancement in the deep posterior compartment of the leg was greater in patients than in controls. The fast enhancement phase in the deep posterior compartment began slightly slower in patients than in controls, but it continued longer. We believe that periosteal edema in bone stress reaction can cause impairment of venous flow in the deep posterior compartment. MRI can depict both these conditions. In patients with medial tibial pain, MR imaging protocol should include axial STIR images (to depict bone pathology) with T1-weighted axial pre and post-contrast images, and dynamic contrast enhanced imaging to show periosteal edema and abnormal contrast enhancement within a compartment.

The nature of very low luminosity objects (VeLLOs)

NASA Astrophysics Data System (ADS)

Vorobyov, Eduard I.; Elbakyan, Vardan; Dunham, Michael M.; Guedel, Manuel

2017-04-01

Aims: The nature of very low luminosity objects (VeLLOs) with the internal luminosity Lobj ≤ 0.1 L⊙ is investigated by means of numerical modeling coupling the core collapse simulations with the stellar evolution calculations. Methods: The gravitational collapse of a large sample of model cores in the mass range 0.1-2.0 M⊙ is investigated. Numerical simulations were started at the pre-stellar phase and terminated at the end of the embedded phase when 90% of the initial core mass had been accreted onto the forming protostar plus disk system. The disk formation and evolution was studied using numerical hydrodynamics simulations, while the formation and evolution of the central star was calculated using a stellar evolution code. Three scenarios for mass accretion from the disk onto the star were considered: hybrid accretion in which a fraction of accreted energy absorbed by the protostar depends on the accretion rate, hot accretion wherein a fraction of accreted energy is constant, and cold accretion wherein all accretion energy is radiated away. Results: Our conclusions on the nature of VeLLOs depend crucially on the character of protostellar accretion. In the hybrid accretion scenario, most VeLLOs (90.6%) are expected to be the first hydrostatic cores (FHSCs) and only a small fraction (9.4%) are true protostars. In the hot accretion scenario, all VeLLOs are FHSCs due to overly high photospheric luminosity of protostars. In the cold accretion scenario, on the contrary, the majority of VeLLOs belong to the Class I phase of stellar evolution. The reason is that the stellar photospheric luminosity, which sets the floor for the total internal luminosity of a young star, is lower in cold accretion, thus enabling more VeLLOs in the protostellar stage. VeLLOs are relatively rare objects occupying 7%-11% of the total duration of the embedded phase and their masses do not exceed 0.3 M⊙. When compared with published observations inferring a fraction of VeLLOs in the protostellar stage of 6.25%, we find that cold accretion provides a much better fit to observations than hybrid accretion (5.7% for cold accretion vs. 0.7% for hybrid accretion). Both accretion scenarios predict more VeLLOs in the Class I phase than in the Class 0 phase, in contrast to observations. Finally, when accretion variability with episodic bursts is artificially filtered out from our numerically derived accretion rates, the fraction of VeLLOs in the protostellar stage drops significantly, suggesting a causal link between the two phenomena.

Melatonin enhances vertical bone augmentation in rat calvaria secluded spaces.

PubMed

Shino, Hiromichi; Hasuike, Akira; Arai, Yoshinori; Honda, Masaki; Isokawa, Keitaro; Sato, Shuichi

2016-01-01

Melatonin has many roles, including bone remodeling and osseointegration of dental implants. The topical application of melatonin facilitated bone regeneration in bone defects. We evaluated the effects of topical application of melatonin on vertical bone augmentation in rat calvaria secluded spaces. In total, 12 male Fischer rats were used and two plastic caps were fixed in the calvarium. One plastic cap was filled with melatonin powder and the other was left empty. Newly generated bone at bone defects and within the plastic caps was evaluated using micro-CT and histological sections. New bone regeneration within the plastic cap was increased significantly in the melatonin versus the control group. Melatonin promoted vertical bone regeneration in rat calvaria in the secluded space within the plastic cap.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

PubMed Central

Zhang, Qing; Miller, Christopher; Bible, Jesse; Li, Jiliang; Xu, Xiaoqing; Mehta, Nozer; Gilligan, James; Vignery, Agnès; Scholz, Jodi A Carlson

2012-01-01

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture. PMID:24710549

Early bone growth on the surface of titanium implants in rat femur is enhanced by an amorphous diamond coating.

PubMed

Jaatinen, Jarkko J P; Korhonen, Rami K; Pelttari, Alpo; Helminen, Heikki J; Korhonen, Hannu; Lappalainen, Reijo; Kröger, Heikki

2011-08-01

Amorphous diamond (AD) is a durable and compatible biomaterial for joint prostheses. Knowledge regarding bone growth on AD-coated implants and their early-stage osseointegration is poor. We investigated bone growth on AD-coated cementless intramedullary implants implanted in rats. Titanium was chosen as a reference due to its well-known performance. We placed AD-coated and non-coated titanium implants (R(a) ≈ 0.2 μm) into the femoral bone marrow of 25 rats. The animals were divided in 2 groups according to implant coating and they were killed after 4 or 12 weeks. The osseointegration of the implants was examined from hard tissue specimens by measuring the new bone formation on their surface. 4 weeks after the operation, the thickness of new bone in the AD-coated group was greater than that in the non-coated group (15.3 (SD 7.1) μm vs. 7.6 (SD 6.0) μm). 12 weeks after the operation, the thickness of new bone was similar in the non-coated group and in the AD-coated group. We conclude that AD coating of femoral implants can enhance bone ongrowth in rats in the acute, early stage after the operation and might be an improvement over earlier coatings.

Anti-DKK1 antibody promotes bone fracture healing through activation of β-catenin signaling

PubMed Central

Jin, Hongting; Wang, Baoli; Li, Jia; Xie, Wanqing; Mao, Qiang; Li, Shan; Dong, Fuqiang; Sun, Yan; Ke, Hua-Zhu; Babij, Philip; Tong, Peijian; Chen, Di

2015-01-01

In this study we investigated if Wnt/β-catenin signaling in mesenchymal progenitor cells plays a role in bone fracture repair and if DKK1-Ab promotes fracture healing through activation of β-catenin signaling. Unilateral open transverse tibial fractures were created in CD1 mice and in β-cateninPrx1ER conditional knockout (KO) and Cre-negative control mice (C57BL/6 background). Bone fracture callus tissues were collected and analyzed by radiography, micro-CT (μCT), histology, biomechanical testing and gene expression analysis. The results demonstrated that treatment with DKK1-Ab promoted bone callus formation and increased mechanical strength during the fracture healing processinCD1 mice. DKK1-Ab enhanced fracture repair by activation of endochondral ossification. The normal rate of bone repair was delayed when the β-catenin gene was conditionally deleted in mesenchymal progenitor cells during the early stages of fracture healing. DKK1-Ab appeared to act through β-catenin signaling to enhance bone repair since the beneficial effect of DKK1-Ab was abrogated in β-cateninPrx1ER conditional KO mice. Further understanding of the signaling mechanism of DKK1-Ab in bone formation and bone regeneration may facilitate the clinical translation of this anabolic agent into therapeutic intervention. PMID:25263522

Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet?

PubMed

Hanley, David A; Whiting, Susan J

2013-01-01

A popular concept in nutrition and lay literature is that of the role of a diet high in acid or protein in the pathogenesis of osteoporosis. A diet rich in fruit and vegetable intake is thought to enhance bone health as the result of its greater potassium and lower "acidic" content than a diet rich in animal protein and sodium. Consequently, there have been a number of studies of diet manipulation to enhance potassium and "alkaline" content of the diet to improve bone density or other parameters of bone health. Although acid loading or an acidic diet featuring a high protein intake may be associated with an increase in calciuria, the evidence supporting a role of these variables in the development of osteoporosis is not consistent. Similarly, intervention studies with a more alkaline diet or use of supplements of potassium citrate or bicarbonate have not consistently shown a bone health benefit. In the elderly, inadequate protein intake is a greater problem for bone health than protein excess. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Recent advances in bone tissue engineering scaffolds

PubMed Central

Bose, Susmita; Roy, Mangal; Bandyopadhyay, Amit

2012-01-01

Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, biodegradable materials that harbor different growth factors, drugs, genes or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. PMID:22939815

Molecular stress-inducing compounds increase osteoclast formation in a heat shock factor 1 protein-dependent manner.

PubMed

Chai, Ryan C; Kouspou, Michelle M; Lang, Benjamin J; Nguyen, Chau H; van der Kraan, A Gabrielle J; Vieusseux, Jessica L; Lim, Reece C; Gillespie, Matthew T; Benjamin, Ivor J; Quinn, Julian M W; Price, John T

2014-05-09

Many anticancer therapeutic agents cause bone loss, which increases the risk of fractures that severely reduce quality of life. Thus, in drug development, it is critical to identify and understand such effects. Anticancer therapeutic and HSP90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) causes bone loss by increasing osteoclast formation, but the mechanism underlying this is not understood. 17-AAG activates heat shock factor 1 (Hsf1), the master transcriptional regulator of heat shock/cell stress responses, which may be involved in this negative action of 17-AAG upon bone. Using mouse bone marrow and RAW264.7 osteoclast differentiation models we found that HSP90 inhibitors that induced a heat shock response also enhanced osteoclast formation, whereas HSP90 inhibitors that did not (including coumermycin A1 and novobiocin) did not affect osteoclast formation. Pharmacological inhibition or shRNAmir knockdown of Hsf1 in RAW264.7 cells as well as the use of Hsf1 null mouse bone marrow cells demonstrated that 17-AAG-enhanced osteoclast formation was Hsf1-dependent. Moreover, ectopic overexpression of Hsf1 enhanced 17-AAG effects upon osteoclast formation. Consistent with these findings, protein levels of the essential osteoclast transcription factor microphthalmia-associated transcription factor were increased by 17-AAG in an Hsf1-dependent manner. In addition to HSP90 inhibitors, we also identified that other agents that induced cellular stress, such as ethanol, doxorubicin, and methotrexate, also directly increased osteoclast formation, potentially in an Hsf1-dependent manner. These results, therefore, indicate that cellular stress can enhance osteoclast differentiation via Hsf1-dependent mechanisms and may significantly contribute to pathological and therapeutic related bone loss.

The Expression of Fn14 via Mechanical Stress-activated JNK Contributes to Apoptosis Induction in Osteoblasts*

PubMed Central

Matsui, Hiroyuki; Fukuno, Naoto; Kanda, Yoshiaki; Kantoh, Yusuke; Chida, Toko; Nagaura, Yuko; Suzuki, Osamu; Nishitoh, Hideki; Takeda, Kohsuke; Ichijo, Hidenori; Sawada, Yasuhiro; Sasaki, Keiichi; Kobayashi, Takayasu; Tamura, Shinri

2014-01-01

Bone mass is maintained by the balance between the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. It is well known that adequate mechanical stress is essential for the maintenance of bone mass, whereas excess mechanical stress induces bone resorption. However, it has not been clarified how osteoblasts respond to different magnitudes of mechanical stress. Here we report that large-magnitude (12%) cyclic stretch induced Ca2+ influx, which activated reactive oxygen species generation in MC3T3-E1 osteoblasts. Reactive oxygen species then activated the ASK1-JNK/p38 pathways. The activated JNK led to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, the ASK1-p38 pathway induced expression of the monocyte chemoattractant protein 3 (MCP-3) gene, which promoted chemotaxis of preosteoclasts. In contrast, the ERK pathway was activated by small-magnitude stretching (1%) and induced expression of two osteogenic genes, collagen Ia (Col1a) and osteopontin (OPN). Moreover, activated JNK suppressed Col1a and OPN induction in large-magnitude mechanical stretch-loaded cells. The enhanced expression of Fn14 and MCP-3 by 12% stretch and the enhanced expression of Col1a and OPN by 1% stretch were also observed in mouse primary osteoblasts. These results suggest that differences in the response of osteoblasts to varying magnitudes of mechanical stress play a key role in switching the mode of bone metabolism between formation and resorption. PMID:24446436

Biomimetic Engineering of Nanofibrous Gelatin Scaffolds with Noncollagenous Proteins for Enhanced Bone Regeneration

PubMed Central

Sun, Yao; Jiang, Yong; Liu, Qilin; Gao, Tian; Feng, Jian Q.; Dechow, Paul; D'Souza, Rena N.; Qin, Chunlin

2013-01-01

Biomimetic approaches are widely used in scaffolding designs to enhance tissue regeneration. In this study, we integrated noncollagenous proteins (NCPs) from bone extracellular matrix (ECM) with three-dimensional nanofibrous gelatin (NF-Gelatin) scaffolds to form an artificial matrix (NF-Gelatin-NCPs) mimicking both the nano-structured architecture and chemical composition of natural bone ECM. Through a chemical coupling process, the NCPs were evenly distributed over all the surfaces (inner and outer) of the NF-gelatin-NCPs. The in vitro study showed that the number of osteoblasts (MC3T3-E1) on the NF-Gelatin-NCPs was significantly higher than that on the NF-Gelatin after being cultured for 14 days. Both the alkaline phosphatase (ALP) activity and the expression of osteogenic genes (OPN, BSP, DMP1, CON, and Runx2) were significantly higher in the NF-Gelatin-NCPs than in the NF-Gelatin at 3 weeks. Von Kossa staining, backscattered scanning electron microscopy, and microcomputed tomography all revealed a higher amount of mineral deposition in the NF-Gelatin-NCPs than in the NF-Gelatin after in vitro culturing for 3 weeks. The in vivo calvarial defect study indicated that the NF-Gelatin-NCPs recruited more host cells to the defect and regenerated a higher amount of bone than the controls after implantation for 6 weeks. Immunohistochemical staining also showed high-level mineralization of the bone matrix in the NF-Gelatin-NCPs. Taken together, both the in vitro and in vivo results confirmed that the incorporation of NCPs onto the surfaces of the NF-Gelatin scaffold significantly enhanced osteogenesis and mineralization. Biomimetic engineering of the surfaces of the NF-Gelatin scaffold with NCPs, therefore, is a promising strategy to enhance bone regeneration. PMID:23469769

Simulating X-ray bursts during a transient accretion event

NASA Astrophysics Data System (ADS)

Johnston, Zac; Heger, Alexander; Galloway, Duncan K.

2018-06-01

Modelling of thermonuclear X-ray bursts on accreting neutron stars has to date focused on stable accretion rates. However, bursts are also observed during episodes of transient accretion. During such events, the accretion rate can evolve significantly between bursts, and this regime provides a unique test for burst models. The accretion-powered millisecond pulsar SAX J1808.4-3658 exhibits accretion outbursts every 2-3 yr. During the well-sampled month-long outburst of 2002 October, four helium-rich X-ray bursts were observed. Using this event as a test case, we present the first multizone simulations of X-ray bursts under a time-dependent accretion rate. We investigate the effect of using a time-dependent accretion rate in comparison to constant, averaged rates. Initial results suggest that using a constant, average accretion rate between bursts may underestimate the recurrence time when the accretion rate is decreasing, and overestimate it when the accretion rate is increasing. Our model, with an accreted hydrogen fraction of X = 0.44 and a CNO metallicity of ZCNO = 0.02, reproduces the observed burst arrival times and fluences with root mean square (rms) errors of 2.8 h, and 0.11× 10^{-6} erg cm^{-2}, respectively. Our results support previous modelling that predicted two unobserved bursts and indicate that additional bursts were also missed by observations.

Guided Bone Regeneration Using Collagen Scaffolds, Growth Factors, and Periodontal Ligament Stem Cells for Treatment of Peri-Implant Bone Defects In Vivo

PubMed Central

Scholz, Malte; Baudisch, Maria; Liese, Jan; Frerich, Bernhard; Lang, Hermann

2017-01-01

Introduction The aim of the study was an evaluation of different approaches for guided bone regeneration (GBR) of peri-implant defects in an in vivo animal model. Materials and Methods In minipigs (n = 15), peri-implant defects around calcium phosphate- (CaP-; n = 46) coated implants were created and randomly filled with (1) blank, (2) collagen/hydroxylapatite/β-tricalcium phosphate scaffold (CHT), (3) CHT + growth factor cocktail (GFC), (4) jellyfish collagen matrix, (5) jellyfish collagen matrix + GFC, (6) collagen powder, and (7) collagen powder + periodontal ligament stem cells (PDLSC). Additional collagen membranes were used for coverage of the defects. After 120 days of healing, bone growth was evaluated histologically (bone to implant contact (BIC;%)), vertical bone apposition (VBA; mm), and new bone height (NBH; %). Results In all groups, new bone formation was seen. Though, when compared to the blank group, no significant differences were detected for all parameters. BIC and NBH in the group with collagen matrix as well as the group with the collagen matrix + GFC were significantly less when compared to the collagen powder group (all: p < 0.003). Conclusion GBR procedures, in combination with CaP-coated implants, will lead to an enhancement of peri-implant bone growth. There was no additional significant enhancement of osseous regeneration when using GFC or PDLSC. PMID:28951742

In Vivo Hypobaric Hypoxia Performed During the Remodeling Process Accelerates Bone Healing in Mice

PubMed Central

Durand, Marjorie; Collombet, Jean-Marc; Frasca, Sophie; Begot, Laurent; Lataillade, Jean-Jacques; Le Bousse-Kerdilès, Marie-Caroline

2014-01-01

We investigated the effects of respiratory hypobaric hypoxia on femoral bone-defect repair in mice because hypoxia is believed to influence both mesenchymal stromal cell (MSC) and hematopoietic stem cell mobilization, a process involved in the bone-healing mechanism. To mimic conditions of non-weight-bearing limb immobilization in patients suffering from bone trauma, our hypoxic mouse model was further subjected to hind-limb unloading. A hole was drilled in the right femur of adult male C57/BL6J mice. Four days after surgery, mice were subjected to hind-limb unloading for 1 week. Seven days after surgery, mice were either housed for 4 days in a hypobaric room (FiO2 at 10%) or kept under normoxic conditions. Unsuspended control mice were housed in either hypobaric or normoxic conditions. Animals were sacrificed on postsurgery day 11 to allow for collection of both contralateral and lesioned femurs, blood, and spleen. As assessed by microtomography, delayed hypoxia enhanced bone-healing efficiency by increasing the closing of the cortical defect and the newly synthesized bone volume in the cavity by +55% and +35%, respectively. Proteome analysis and histomorphometric data suggested that bone-repair improvement likely results from the acceleration of the natural bone-healing process rather than from extended mobilization of MSC-derived osteoprogenitors. Hind-limb unloading had hardly any effect beyond delayed hypoxia-enhanced bone-healing efficiency. PMID:24944208

Role of Cbl-PI3K Interaction during Skeletal Remodeling in a Murine Model of Bone Repair.

PubMed

Scanlon, Vanessa; Soung, Do Yu; Adapala, Naga Suresh; Morgan, Elise; Hansen, Marc F; Drissi, Hicham; Sanjay, Archana

2015-01-01

Mice in which Cbl is unable to bind PI3K (YF mice) display increased bone volume due to enhanced bone formation and repressed bone resorption during normal bone homeostasis. We investigated the effects of disrupted Cbl-PI3K interaction on fracture healing to determine whether this interaction has an effect on bone repair. Mid-diaphyseal femoral fractures induced in wild type (WT) and YF mice were temporally evaluated via micro-computed tomography scans, biomechanical testing, histological and histomorphometric analyses. Imaging analyses revealed no change in soft callus formation, increased bony callus formation, and delayed callus remodeling in YF mice compared to WT mice. Histomorphometric analyses showed significantly increased osteoblast surface per bone surface and osteoclast numbers in the calluses of YF fractured mice, as well as increased incorporation of dynamic bone labels. Furthermore, using laser capture micro-dissection of the fracture callus we found that cells lacking Cbl-PI3K interaction have higher expression of Osterix, TRAP, and Cathepsin K. We also found increased expression of genes involved in propagating PI3K signaling in cells isolated from the YF fracture callus, suggesting that the lack of Cbl-PI3K interaction perhaps results in enhanced PI3K signaling, leading to increased bone formation, but delayed remodeling in the healing femora.

Guided Bone Regeneration Using Collagen Scaffolds, Growth Factors, and Periodontal Ligament Stem Cells for Treatment of Peri-Implant Bone Defects In Vivo.

PubMed

Kämmerer, Peer W; Scholz, Malte; Baudisch, Maria; Liese, Jan; Wegner, Katharina; Frerich, Bernhard; Lang, Hermann

2017-01-01

The aim of the study was an evaluation of different approaches for guided bone regeneration (GBR) of peri-implant defects in an in vivo animal model. In minipigs ( n = 15), peri-implant defects around calcium phosphate- (CaP-; n = 46) coated implants were created and randomly filled with (1) blank, (2) collagen/hydroxylapatite/ β -tricalcium phosphate scaffold (CHT), (3) CHT + growth factor cocktail (GFC), (4) jellyfish collagen matrix, (5) jellyfish collagen matrix + GFC, (6) collagen powder, and (7) collagen powder + periodontal ligament stem cells (PDLSC). Additional collagen membranes were used for coverage of the defects. After 120 days of healing, bone growth was evaluated histologically (bone to implant contact (BIC;%)), vertical bone apposition (VBA; mm), and new bone height (NBH; %). In all groups, new bone formation was seen. Though, when compared to the blank group, no significant differences were detected for all parameters. BIC and NBH in the group with collagen matrix as well as the group with the collagen matrix + GFC were significantly less when compared to the collagen powder group (all: p < 0.003). GBR procedures, in combination with CaP-coated implants, will lead to an enhancement of peri-implant bone growth. There was no additional significant enhancement of osseous regeneration when using GFC or PDLSC.

Accretion onto a charged Kiselev black hole

NASA Astrophysics Data System (ADS)

Abbas, G.; Ditta, A.

2018-04-01

Accretion of matter onto a compact is one of the interesting astrophysical processes. Here, we study the accretion of matter onto a charged Kiselev black hole. The problem of static and spherically symmetric accretion of a polytropic fluid is explored for the analytic solution of equations of motion. We have investigated the necessary conditions for existence of the critical flow points and the mass accretion rate. Finally, we discuss the polytropic gas accretion in detail. It has been found that in the accretion process the quintessence and charge parameters play a dominant role.

Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

PubMed

Kamikura, Keita; Minatoya, Tsutomu; Terada-Nakaishi, Michiko; Yamamoto, Shoko; Sakai, Yasuo; Furusawa, Toshitake; Matsushima, Yuta; Unuma, Hidero

2017-09-01

It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

Highly porous hydroxyapatite with and without local harvested bone in sinus floor augmentation: a histometric study in pigs.

PubMed

Möller, Björn; Acil, Yahya; Birkenfeld, Falk; Behrens, Eleonore; Terheyden, Hendrik; Wiltfang, Jörg

2014-07-01

Sinus floor augmentation with autologous bone is an accepted treatment option in dental implantology. In this study, an entirely synthetic, nano-structured, hydroxyapatite-based bone substitute material (SBSM, NanoBone(®); Artoss, Rostock, Germany) was supplemented with a mixture of locally harvested bone to enhance osteogenesis. Bilateral sinus augmentation procedures were performed in eight domestic pigs using the lateral window technique. On the right side (control), 2.6 ml of SBSM was used, and on the left side (test), 2.6 ml of SBSM with additional 15% (390 μl) autologous bone was used. At the time of augmentation, a titanium implant (ITI(®)) was inserted from a laterocaudal direction. After 3 months, the sites of augmentation were removed and examined in non-decalcified sections by microradiography and fluorescence microscopy of sequentially labelled specimens and histometry. On both sides, a significant amount of newly formed bone was observed. However, a statistically significant difference in the bone-implant contact was observed in the control group (median, 28.9%) compared with the test side with the additional autologous bone (median, 40.6%) (P = 0.01). Different bone density was achieved from the coronal to apical surfaces (medians, 54.6%, 9.6%, and 27.5%) compared with the test side (medians, 55.2%, 40.6%, and 44.2%). The median of augmentation height was 8.6 mm on the control side and 11.5 mm on the test side (P = 0.01). Bone apposition was observed in both groups after 15 days. The SBSM shows acceptable results in sinus floor augmentation. The additional use of locally harvested autologous bone enhances bone density and osseointegration of the implants. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Action Mechanism of Fibroblast Growth Factor-2 (FGF-2) in the Promotion of Periodontal Regeneration in Beagle Dogs

PubMed Central

Nagayasu-Tanaka, Toshie; Anzai, Jun; Takaki, Shu; Shiraishi, Noriko; Terashima, Akio; Asano, Taiji; Nozaki, Takenori; Kitamura, Masahiro; Murakami, Shinya

2015-01-01

Fibroblast growth factor-2 (FGF-2) enhances the formation of new alveolar bone, cementum, and periodontal ligament (PDL) in periodontal defect models. However, the mechanism through which FGF-2 acts in periodontal regeneration in vivo has not been fully clarified yet. To reveal the action mechanism, the formation of regenerated tissue and gene expression at the early phase were analyzed in a beagle dog 3-wall periodontal defect model. FGF-2 (0.3%) or the vehicle (hydroxypropyl cellulose) only were topically applied to the defect in FGF-2 and control groups, respectively. Then, the amount of regenerated tissues and the number of proliferating cells at 3, 7, 14, and 28 days and the number of blood vessels at 7 days were quantitated histologically. Additionally, the expression of osteogenic genes in the regenerated tissue was evaluated by real-time PCR at 7 and 14 days. Compared with the control, cell proliferation around the existing bone and PDL, connective tissue formation on the root surface, and new bone formation in the defect at 7 days were significantly promoted by FGF-2. Additionally, the number of blood vessels at 7 days was increased by FGF-2 treatment. At 28 days, new cementum and PDL were extended by FGF-2. Moreover, FGF-2 increased the expression of bone morphogenetic protein 2 (BMP-2) and osteoblast differentiation markers (osterix, alkaline phosphatase, and osteocalcin) in the regenerated tissue. We revealed the facilitatory mechanisms of FGF-2 in periodontal regeneration in vivo. First, the proliferation of fibroblastic cells derived from bone marrow and PDL was accelerated and enhanced by FGF-2. Second, angiogenesis was enhanced by FGF-2 treatment. Finally, osteoblastic differentiation and bone formation, at least in part due to BMP-2 production, were rapidly induced by FGF-2. Therefore, these multifaceted effects of FGF-2 promote new tissue formation at the early regeneration phase, leading to enhanced formation of new bone, cementum, and PDL. PMID:26120833

Sclerostin's role in bone's adaptive response to mechanical loading.

PubMed

Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

2017-03-01

Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A model for accretion of the terrestrial planets

NASA Technical Reports Server (NTRS)

Weidenschilling, S. J.

1974-01-01

One possible origin of the terrestrial planets involves their formation by gravitational accretion of particles originally in Keplerian orbits about the sun. Some implications of this theory are considered. A formal expression for the rate of mass accretion by a planet is developed. The formal singularity of the gravitational collision cross section for low relative velocities is shown to be without physical significance when the accreting bodies are in heliocentric orbits. The distribution of particle velocities relative to an accreting planet is considered; the mean velocity increases with time. The internal temperature of an accreting planet is shown to depend simply on the accretion rate. A simple and physically reasonable approximate expression for a planetary accretion rate is proposed.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brady, Robert T.; Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin; Advanced Materials and BioEngineering Research Centre

Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferationmore » and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting secretome between osteocytes and osteoblasts.« less

Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized control trial

USDA-ARS?s Scientific Manuscript database

Although consuming dietary protein above current recommendations during energy deficit enhances blood lipid profiles and preserves lean body mass, concerns have been raised regarding effects of high-protein diets on bone health. To determine whether calcium homeostasis and bone turnover are affected...

Infant formula promotes bone growth in neonatal piglets by enhancing osteoblastogenesis through bone morphogenic protein signaling

USDA-ARS?s Scientific Manuscript database

Relatively few studies have examined the effects of formula feeding relative to breast-feeding on bone in the neonate. Using peripheral quantitative CT scan and histomorphometric analysis, we demonstrated that neonatal piglets fed with soy-based formula (SF) and cow milk-based formula (MF) for 21 or...

Flares, Magnetic Reconnections and Accretion Disk Viscosity

NASA Astrophysics Data System (ADS)

Welsh, William

2001-07-01

Accretion disks are invoked to explain a host of astrophysical phenomena, from protostellar objects to AGN. And yet the mechanism allowing accretion disks to operate are completely unknown. This proposal seeks to observe the ``smoking gun'' signature of magnetically-driven viscosity in accretion disks. Magnetically-induced viscosity is a plausible and generally accepted hypothesis {for esthetic reasons}, but it is completely untested. Determining the cause of accretion disk viscosity is of major significance to all accretion-disk powered systems {e.g. CVs, X-ray binaries, AGN and protostellar disks}. These data will also firmly establish the importance of magnetic fields in accretion disks. Because of its known flaring properites, we will observe the accretion disk in EM Cyg simulataneously with STIS/FUV and CHANDRA. The simultaneous X-rays are absolutely necessary for the unambiguous detection of accretion disk magnetic reconnection flares.

Design of calcium phosphate ceramics for drug delivery applications in bone diseases: A review of the parameters affecting the loading and release of the therapeutic substance.

PubMed

Parent, Marianne; Baradari, Hiva; Champion, Eric; Damia, Chantal; Viana-Trecant, Marylène

2017-04-28

Effective treatment of critical-size defects is a key challenge in restorative surgery of bone. The strategy covers the implantation of biocompatible, osteoconductive, bioactive and biodegradable devices which (1) well interact with native tissue, mimic multi-dimensional and hierarchical structure of bone and (2) are able to enhance bone repair, treating post implantation pathologies or bone diseases by local delivery of therapeutic agents. Among different options, calcium phosphate biomaterials are found to be attractive choices, due to their excellent biocompatibility, customisable bioactivity and biodegradability. Several approaches have been established to enhance this material ability to be loaded with a therapeutic agent, in order to obtain an in situ controlled release that meets the clinical needs. This article reviews the most important factors influencing on both drug loading and release capacity of porous calcium phosphate bone substitutes. Characteristics of the carrier, drug/carrier interactions, experimental conditions of drug loading and evaluation of drug delivery are considered successively. Copyright © 2017 Elsevier B.V. All rights reserved.

Nano-engineered titanium for enhanced bone therapy

NASA Astrophysics Data System (ADS)

Gulati, Karan; Atkins, Gerald J.; Findlay, David M.; Losic, Dusan

2013-09-01

Current treatment of a number of orthopaedic conditions, for example fractures, bone infection, joint replacement and bone cancers, could be improved if mechanical support could be combined with drug delivery. A very challenging example is that of infection following joint replacement, which is very difficult to treat, can require multiple surgeries and compromises both the implant and the patient's wellbeing. An implant capable of providing appropriate biomechanics and releasing drugs/proteins locally might ensure improved healing of the traumatized bone. We propose fabrication of nanoengineered titanium bone implants using bioinert titanium wires in order to achieve this goal. Titanium in the form of flat foils and wires were modified by fabrication of titania nanotubes (TNTs), which are hollow self-ordered cylindrical tubes capable of accommodating substantial drug amounts and releasing them locally. To further control the release of drug to over a period of months, a thin layer of biodegradable polymer PLGA poly(lactic-coglycolic acid) was coated onto the drug loaded TNTs. This delayed release of drug and additionally the polymer enhanced bone cell adhesion and proliferation.

Functional reconstruction of critical-sized load-bearing bone defects using a Sclerostin-targeting miR-210-3p-based construct to enhance osteogenic activity.

PubMed

Hu, Bin; Li, Yan; Wang, Mohan; Zhu, Youming; Zhou, Yong; Sui, Baiyan; Tan, Yu; Ning, Yujie; Wang, Jie; He, Jiacai; Yang, Chi; Zou, Duohong

2018-06-10

A considerable amount of research has focused on improving regenerative therapy strategies for repairing defects in load-bearing bones. The enhancement of tissue regeneration with microRNAs (miRNAs) is being developed because miRNAs can simultaneously regulate multiple signaling pathways in an endogenous manner. In this study, we developed a miR-210-based bone repair strategy. We identified a miRNA (miR-210-3p) that can simultaneously up-regulate the expression of multiple key osteogenic genes in vitro. This process resulted in enhanced bone formation in a subcutaneous mouse model with a miR-210-3p/poly-L-lactic acid (PLLA)/bone marrow-derived stem cell (BMSC) construct. Furthermore, we constructed a model of critical-sized load-bearing bone defects and implanted a miR-210-3p/β-tricalcium phosphate (β-TCP)/bone mesenchymal stem cell (BMSC) construct into the defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. We also identified a new mechanism by which miR-210-3p regulates Sclerostin protein levels. This miRNA-based strategy may yield novel therapeutic methods for the treatment of regenerative defects in vital load-bearing bones by utilizing miRNA therapy for tissue engineering. The destroyed maxillofacial bone reconstruction is still a real challenge for maxillofacial surgeon, due to that functional bone reconstruction involved load-bearing. Base on the above problem, this paper developed a novel miR-210-3p/β-tricalcium phosphate (TCP)/bone marrow-derived stem cell (BMSC) construct (miR-210-3p/β-TCP/BMSCs), which lead to functional reconstruction of critical-size mandible bone defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. In addition, we also found the mechanism of how the delivered microRNA activated the signaling pathways of endogenous stem cells, leading to the defect regeneration. This miRNA-based strategy can be used to regenerate defects in vital load-bearing bones, thus addressing a critical challenge in regenerative medicine by utilizing miRNA therapy for tissue engineering. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Emerging Paradigm of Pebble Accretion

NASA Astrophysics Data System (ADS)

Ormel, Chris W.

Pebble accretion is the mechanism in which small particles ("pebbles") accrete onto big bodies big (planetesimals or planetary embryos) in gas-rich environments. In pebble accretion accretion , accretion occurs by settling and depends only on the mass of the gravitating body gravitating , not its radius. I give the conditions under which pebble accretion operates and show that the collisional cross section can become much larger than in the gas-free, ballistic, limit. In particular, pebble accretion requires the pre-existence of a massive planetesimal seed. When pebbles experience strong orbital decay by drift motions or are stirred by turbulence, the accretion efficiency is low and a great number of pebbles are needed to form Earth-mass cores. Pebble accretion is in many ways a more natural and versatile process than the classical, planetesimal-driven paradigm, opening up avenues to understand planet formation in solar and exoplanetary systems.

Accretion onto CO White Dwarfs using MESA

NASA Astrophysics Data System (ADS)

Feng, Wanda; Starrfield, Sumner

2018-06-01

The nature of type Ia Supernovae (SNe Ia) progenitor systems and their underlying mechanism are not well understood. There are two competing progenitor scenarios: the single-degenerate scenario wherein a white dwarf (WD) star accretes material from a companion star, reaching the Chandrasekhar mass limit; and, the double-degenerate scenario wherein two WDs merge. In this study, we investigate the single-degenerate scenario by accretion onto carbon-oxygen (CO) WDs using the Modules for Experiments in Stellar Astrophysics (MESA). We vary the WD mass, composition of the accreting material, and accretion rate in our models. Mixing between the accreted material and the WD core is informed by multidimensional studies that suggest occurance after thermonuclear runaway (TNR) ensues. We compare the accretion of solar composition material onto CO WDs with the accretion of mixed solar and core material after TNR. As many of our models eject less material than accreted, our study supports that accretion onto CO WDs is a feasible channel for SNe I progenitors.

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects

PubMed Central

Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

2015-01-01

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m2/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration. PMID:25609957

Concise review: Insights from normal bone remodeling and stem cell-based therapies for bone repair.

PubMed

Khosla, Sundeep; Westendorf, Jennifer J; Mödder, Ulrike I

2010-12-01

There is growing interest in the use of mesenchymal stem cells for bone repair. As a major reason for normal bone remodeling is the removal of fatigue microcracks, advances in our understanding of this process may inform approaches to enhance fracture healing. Increasing evidence now indicates that physiological bone remodeling occurs in close proximity to blood vessels and that these vessels carry perivascular stem cells that differentiate into osteoblasts. Similarly, fracture healing is critically dependent on the ingrowth of blood vessels not only for a nutrient supply but also for the influx of osteoblasts. A number of animal and human studies have now shown the potential benefit of bone marrow-derived mesenchymal stem cells in enhancing bone repair. However, as in other tissues, the question of whether these cells improve fracture healing directly by differentiating into osteoblasts or indirectly by secreting paracrine factors that recruit blood vessels and the accompanying perivascular stem cells remains a major unresolved issue. Moreover, CD34+ cells, which are enriched for endothelial/hematopoietic cells, have also shown efficacy in various bone repair models, at least in part due to the induction of angiogenesis and recruitment of host progenitor cells. Thus, mesenchymal and nonmesenchymal stem/progenitor cells are attractive options for bone repair. It is possible that they contribute directly to bone repair, but it is also likely that they express paracrine factors in the appropriate amounts and combinations that promote and sustain the healing process.

Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive G{sub s}–G protein signaling in osteoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wattanachanya, Lalita, E-mail: lalita_md@yahoo.com; Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok; Wang, Liping, E-mail: lipingwang05@yahoo.com

G protein-coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active G{sub s}-coupled GPCR, under the control of the 2.3 kb Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone of femurs. Here, we further evaluated the effects of enhanced G{sub s} signaling in OBs on intramembranous bone formation by examining calvariae of 1- and 9-week-old Col1(2.3)/Rs1 mice and characterized the in vivo gene expression specifically occurring in osteoblasts with activated G{sub s} G protein-coupled receptor signaling, at the cellularmore » level rather than in a whole bone. Rs1 calvariae displayed a dramatic increase in bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space while Osteocalcin was expressed predominantly in cells along bone surfaces, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb Col I promoter could influence early OB commitment, differentiation, and/or proliferation. Gene expression analysis of calvarial OBs revealed that genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. The set of G{sub s}-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of G{sub s} signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to G{sub s} signaling in mature OBs. - Highlights: • OB expression of an engineered G{sub s}-coupled receptor dramatically increases bone mass. • We investigated the changes in gene expression in vivo in enhanced OB G{sub s} signaling. • Genes in cell cycle and transcription were increased in enhanced OB G{sub s} signaling. • GPCRs and paracrine mediators of the effect of G{sub s} signaling in OBs were determined.« less

Decision tree analysis as a supplementary tool to enhance histomorphological differentiation when distinguishing human from non-human cranial bone in both burnt and unburnt states: A feasibility study.

PubMed

Simmons, T; Goodburn, B; Singhrao, S K

2016-01-01

This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non-human bones. Reference series of fully mineralized, transverse sections of cranial bone, from all variables and specimen states, were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non-humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non-human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions. © The Author(s) 2015.

A feasibility study for in vitro evaluation of fixation between prosthesis and bone with bone marrow-derived mesenchymal stem cells.

PubMed

Morita, Yusuke; Yamasaki, Kenichi; Hattori, Koji

2010-10-01

It is difficult to quantitatively evaluate adhesive strength between an implant and the neighboring bone using animal experiments, because the degree of fixation of an implant depends on differences between individuals and the clearance between the material and the bone resulting from surgical technique. A system was designed in which rat bone marrow cells were used to quantitatively evaluate the adhesion between titanium alloy plates and bone plates in vitro. Three kinds of surface treatment were used: a sand-blasted surface, a titanium-sprayed surface and a titanium-sprayed surface coated with hydroxyapatite. Bone marrow cells obtained from rat femora were seeded on the titanium alloy plates, and the cells were cultured between the titanium alloy plates and the bone plates sliced from porcine ilium for 2 weeks. After cultivation, adhesive strength was measured using a tensile test, after which DNA amount and Alkaline phosphatase activity were measured. The seeded cells accelerated adhesion of the titanium alloy plate to the bone plate. Adhesive strength of the titanium-sprayed surface was lower than that of the sand-blasted surface because of lower initial contact area, although there was no difference in Alkaline phosphatase activity between two surface treatments. A hydroxyapatite coating enhanced adhesive strength between the titanium alloy palate and the bone plate, as well as enhancing osteogenic differentiation of bone marrow cells. It is believed that this novel experimental method can be used to simultaneously evaluate the osteogenic differentiation and the adhesive strength of an implant during in vitro cultivation. 2010 Elsevier Ltd. All rights reserved.

Calcium phosphate cements for bone engineering and their biological properties

PubMed Central

Xu, Hockin HK; Wang, Ping; Wang, Lin; Bao, Chongyun; Chen, Qianming; Weir, Michael D; Chow, Laurence C; Zhao, Liang; Zhou, Xuedong; Reynolds, Mark A

2017-01-01

Calcium phosphate cements (CPCs) are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre-vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis. PMID:29354304

Thin Disks Gone MAD: Magnetically Arrested Accretion in the Thin Regime

NASA Astrophysics Data System (ADS)

Avara, Mark J.; McKinney, Jonathan C.; Reynolds, Christopher S.

2015-01-01

The collection and concentration of surrounding large scale magnetic fields by black hole accretion disks may be required for production of powerful, spin driven jets. So far, accretion disks have not been shown to grow sufficient poloidal flux via the turbulent dynamo alone to produce such persistent jets. Also, there have been conflicting answers as to how, or even if, an accretion disk can collect enough magnetic flux from the ambient environment. Extending prior numerical studies of magnetically arrested disks (MAD) in the thick (angular height, H/R~1) and intermediate (H/R~.2-.6) accretion regimes, we present our latest results from fully general relativistic MHD simulations of the thinnest BH (H/R~.1) accretion disks to date exhibiting the MAD mode of accretion. We explore the significant deviations of this accretion mode from the standard picture of thin, MRI-driven accretion, and demonstrate the accumulation of large-scale magnetic flux.

The effect of accretion environment at large radius on hot accretion flows

NASA Astrophysics Data System (ADS)

Yang, Xiao-Hong; Bu, De-Fu

2018-05-01

We study the effects of accretion environment (gas density, temperature, and angular momentum) at large radii (˜10 pc) on luminosity of hot accretion flows. The radiative feedback effects from the accretion flow on the accretion environment are also self-consistently taken into account. We find that the slowly rotating flows at large radii can significantly deviate from Bondi accretion when radiation heating and cooling are considered. We further find that when the temperature of environment gas is low (e.g. T = 2 × 107 K), the luminosity of hot accretion flows is high. When the temperature of gas is high (e.g. T ≥ 4 × 107 K), the luminosity of hot accretion flow significantly deceases. The environment gas density can also significantly influence the luminosity of accretion flows. When density is higher than ˜4 × 10-22 g cm-3 and temperature is lower than 2 × 107 K, hot accretion flow with luminosity lower than 2 per cent LEdd is not present. Therefore, the parsec-scale environment density and temperature are two important parameters to determine the luminosity. The results are also useful for the subgrid models adopted by the cosmological simulations.

A Preliminary Evaluation of Lyophilized Gelatin Sponges, Enhanced with Platelet-Rich Plasma, Hydroxyapatite and Chitin Whiskers for Bone Regeneration

PubMed Central

Rodriguez, Isaac A.; Sell, Scott A.; McCool, Jennifer M.; Saxena, Gunjan; Spence, Andrew J.; Bowlin, Gary L.

2013-01-01

The purpose of this study was to perform a number of preliminary in vitro evaluations on an array of modified gelatin gel sponge scaffolds for use in a bone graft application. The gelatin gels were modified through the addition of a number of components which each possess unique properties conducive to the creation and regeneration of bone: a preparation rich in growth factors (PRGF, a bioactive, lyophilized form of platelet-rich plasma), hydroxyapatite, and chitin whiskers. Platelet-rich plasma therapy is an emerging practice that has proven effective in a number of clinical applications, including enhancing bone repair through improved deposition of new bony matrix and angiogenesis. As such, the inclusion of PRGF in our gelatin scaffolds was intended to significantly enhance scaffold bioactivity, while the addition of hydroxyapatite and chitin whiskers were anticipated to increase scaffold strength. Additionally, the gelatin sponges, which readily dissolve in aqueous solutions, were subjected to 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linking, either during or post-gelation, to control their rate of degradation. Scaffolds were evaluated in vitro with respect to compressive strength, mass loss/degradation, protein release, and cellular interaction, with results demonstrating the potential of the gelatin gel sponge scaffold for use in the regeneration of bone. PMID:24709699

Inulin and oligofructose and mineral metabolism: the evidence from animal trials.

PubMed

Scholz-Ahrens, Katharina E; Schrezenmeir, Jürgen

2007-11-01

Nondigestible oligosaccharides have been shown to increase the absorption of several minerals (calcium, magnesium, in some cases phosphorus) and trace elements (mainly copper, iron, zinc). Inulin-type fructans including oligofructose and fructooligosaccharides derived from sucrose by enzymatic transfructosylation are the best investigated food ingredients in this respect. The stimulation of absorption was more pronounced when the demand for calcium was high, i.e., in animals in the rapid growing stage and in animals with impaired calcium absorption because of either ovariectomy or gastrectomy. Even a small stimulation of calcium absorption increased the mineral accumulation in the skeleton because of its persisting effect over months. Inulin-type fructans stimulated mineral absorption and bone mineral accretion when combined with probiotic lactobacilli and in the presence of antibiotics. Direct comparison of different inulin-type fructans revealed a more pronounced effect by inulin or a mixture of long-chain inulin and oligofructose than by oligofructose alone. Mechanisms on how inulin-type fructans mediate this effect include acidification of the intestinal lumen by short-chain fatty acids increasing solubility of minerals in the gut, enlargement of the absorption surface, increased expression of calcium-binding proteins mainly in the large intestine, modulated expression of bone-relevant cytokines, suppression of bone resorption, increased bioavailability of phytoestrogens, and, via stimulation of beneficial commensal microorganisms, increase of calcium uptake by enterocytes. Under certain conditions, inulin-type fructans may improve mineral absorption by their impact on the amelioration of gut health including stabilization of the intestinal flora and reduction of inflammation. The abundance of reports indicate that inulin-type fructans are promising substances that could help to improve the supply with available calcium in human nutrition and by this contribute to bone health.

Prevention of disuse osteoporosis: Effect of sodium fluoride during five weeks of bed rest

NASA Technical Reports Server (NTRS)

Schneider, Victor S.

1987-01-01

An attempt was made to modify factors which promote disuse osteoporosis and thereby prevent it from occurring. Since fluoride is currently used to enhance bone formation in the treatment of low turnover osteoporosis, it was hypothesized that if the fluoride ion was available over a long period of time that it would slow the demonstrated loss of calcium by inhibiting bone resorption and enhancing bone formation. This study was used to determine whether oral medication with sodium F will modify or prevent 5 weeks of bed rest induced disuse osteoporosis, to determine the longitudinal effects of 5 weeks of bed rest on PTH, CT and calcitriol, to measure muscle volume changes and metabolic activity by magnetic resonance imaging and magnetic resonance spectroscopy during prolonged bed rest, to measure changes in peak muscle strength and fatigability, and to measure bone turnover in bone biopsies. Subjects were studied during 1 week of equilibration, 4 weeks of control ambulation, 5 weeks of bed rest, and 1 week of reambulation.

Effect of resistance training with vibration and compression on the formation of muscle and bone.

PubMed

Zinner, Christoph; Baessler, Bettina; Weiss, Kilian; Ruf, Jasmine; Michels, Guido; Holmberg, Hans-Christer; Sperlich, Billy

2017-12-01

In this study we investigated the effects of resistance training with vibration in combination with leg compression to restrict blood flow on strength, muscle oxygenation, muscle mass, and bone formation. Twelve participants were tested before and after 12 weeks of resistance training with application of vibration (VIBRA; 1-2 mm, 30 Hz) to both legs and compression (∼35 mm Hg, VIBRA+COMP) to only 1 leg. VIBRA+COMP and VIBRA improved 1 repetition maximum (1-RM), increased the number of repetitions preceding muscle exhaustion, enhanced cortical bone mass, and lowered the mass and fat fraction in the thigh, with no changes in total muscle mass. The mass of cancellous bone decreased to a similar extent after VIBRA and VIBRA+COMP. Resistance training with VIBRA+COMP and VIBRA improved 1-RM, increased the number of repetitions preceding muscular exhaustion, and enhanced formation of cortical bone, with no alteration of muscle mass. Muscle Nerve 56: 1137-1142, 2017. © 2017 Wiley Periodicals, Inc.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

PubMed

Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

2006-03-07

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

In vitro characterizations of mesoporous hydroxyapatite as a controlled release delivery device for VEGF in orthopedic applications.

PubMed

Poh, Chye Khoon; Ng, Suxiu; Lim, Tee Yong; Tan, Hark Chuan; Loo, Joachim; Wang, Wilson

2012-11-01

Following bone implant surgery, prolonged ischemic conditions at the implant site often result in postsurgical complications like failure of osseointegration at the bone-implant interface which can lead to implant failure. Thus, restoration of the vascular supply is paramount to the proper development of the bone. High surface area mesostructured materials have been shown to be attractive candidates for bone regeneration to enhance cell adhesion and cell proliferation. This study uses hydroxyapatite, a naturally occurring mineral in the bone, fabricated to a range of suitable pore sizes, infused with vascular endothelial growth factor (VEGF), to be progressively released to stimulate revascularization. In this study, several characterizations including nitrogen adsorption analysis, Fourier-transformed infrared spectroscopy, X-ray diffraction, field emission scanning electron microscope, and transmission electron microscope were used to evaluate the synthesized mesoporous hydroxyapatite (MHA). The results showed that MHA can gradually release VEGF for enhancing revascularization, which is beneficial for orthopedic applications. Copyright © 2012 Wiley Periodicals, Inc.

Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

NASA Astrophysics Data System (ADS)

Wagner, A.; Sachse, A.; Keller, M.; Aurich, M.; Wetzel, W.-D.; Hortschansky, P.; Schmuck, K.; Lohmann, M.; Reime, B.; Metge, J.; Arfelli, F.; Menk, R.; Rigon, L.; Muehleman, C.; Bravin, A.; Coan, P.; Mollenhauer, J.

2006-03-01

Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tovmassian, G.; González–Buitrago, D.; Zharikov, S.

We studied two objects identified as cataclysmic variables (CVs) with periods exceeding the natural boundary for Roche-lobe-filling zero-age main sequence (ZAMS) secondary stars. We present observational results for V1082 Sgr with a 20.82 hr orbital period, an object that shows a low luminosity state when its flux is totally dominated by a chromospherically active K star with no signs of ongoing accretion. Frequent accretion shutoffs, together with characteristics of emission lines in a high state, indicate that this binary system is probably detached, and the accretion of matter on the magnetic white dwarf takes place through stellar wind from themore » active donor star via coupled magnetic fields. Its observational characteristics are surprisingly similar to V479 And, a 14.5 hr binary system. They both have early K-type stars as donor stars. We argue that, similar to the shorter-period prepolars containing M dwarfs, these are detached binaries with strong magnetic components. Their magnetic fields are coupled, allowing enhanced stellar wind from the K star to be captured and channeled through the bottleneck connecting the two stars onto the white dwarf’s magnetic pole, mimicking a magnetic CV. Hence, they become interactive binaries before they reach contact. This will help to explain an unexpected lack of systems possessing white dwarfs with strong magnetic fields among detached white+red dwarf systems.« less

Magnetic Stress at the Marginally Stable Orbit: Altered Disk Structure, Radiation, and Black Hole Spin Evolution

NASA Astrophysics Data System (ADS)

Agol, Eric; Krolik, Julian H.

2000-01-01

Magnetic connections to the plunging region can exert stresses on the inner edge of an accretion disk around a black hole. We recompute the relativistic corrections to the thin-disk dynamics equations when these stresses take the form of a time-steady torque on the inner edge of the disk. The additional dissipation associated with these stresses is concentrated relatively close outside the marginally stable orbit, scaling as r-7/2 at large radius. As a result of these additional stresses, spin-up of the central black hole is retarded; the maximum spin-equilibrium accretion efficiency is 36% and occurs at a/M=0.94 the disk spectrum is extended toward higher frequencies; line profiles (such as Fe Kα) are broadened if the line emissivity scales with local flux; limb brightening, especially at the higher frequencies, is enhanced; and the returning radiation fraction is substantially increased, up to 58%. This last effect creates possible explanations for both synchronized continuum fluctuations in active galactic nuclei and polarization rises shortward of the Lyman edge in quasars. We show that no matter what additional stresses occur, when a/M<0.36, the second law of black hole dynamics sets an absolute upper bound on the accretion efficiency.

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia

PubMed Central

Mayurasakorn, Korapat; Williams, Jill J.; Ten, Vadim S.; Deckelbaum, Richard J.

2014-01-01

Purpose of review With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. Recent findings DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between pre-and post-synaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing anti-apoptotic activities such as decreasing responses to reactive oxygen species, up-regulating anti-apoptotic protein expression, down-regulating apoptotic protein expression, and maintaining mitochondrial integrity and function. Summary DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression. PMID:21178607

Stratified Simulations of Collisionless Accretion Disks

NASA Astrophysics Data System (ADS)

Hirabayashi, Kota; Hoshino, Masahiro

2017-06-01

This paper presents a series of stratified-shearing-box simulations of collisionless accretion disks in the recently developed framework of kinetic magnetohydrodynamics (MHD), which can handle finite non-gyrotropy of a pressure tensor. Although a fully kinetic simulation predicted a more efficient angular-momentum transport in collisionless disks than in the standard MHD regime, the enhanced transport has not been observed in past kinetic-MHD approaches to gyrotropic pressure anisotropy. For the purpose of investigating this missing link between the fully kinetic and MHD treatments, this paper explores the role of non-gyrotropic pressure and makes the first attempt to incorporate certain collisionless effects into disk-scale, stratified disk simulations. When the timescale of gyrotropization was longer than, or comparable to, the disk-rotation frequency of the orbit, we found that the finite non-gyrotropy selectively remaining in the vicinity of current sheets contributes to suppressing magnetic reconnection in the shearing-box system. This leads to increases both in the saturated amplitude of the MHD turbulence driven by magnetorotational instabilities and in the resultant efficiency of angular-momentum transport. Our results seem to favor the fast advection of magnetic fields toward the rotation axis of a central object, which is required to launch an ultra-relativistic jet from a black hole accretion system in, for example, a magnetically arrested disk state.

Exploring the Effects of Disk Thickness on the Black Hole Reflection Spectrum

NASA Astrophysics Data System (ADS)

Taylor, Corbin; Reynolds, Christopher S.

2018-03-01

The relativistically broadened reflection spectrum, observed in both AGN and X-ray binaries, has proven to be a powerful probe of the properties of black holes and the environments in which they reside. Emitted from the innermost regions of the accretion disk, this X-ray spectral component carries with it information not only about the plasma that resides in these extreme conditions, but also the black hole spin, a marker of the formation and accretion history of these objects. The models currently used to interpret the reflection spectrum are often simplistic, however, approximating the disk as an infinitely thin, optically thick plane of material orbiting in circular Keplerian orbits around the central object. Using a new relativistic ray-tracing suite (Fenrir) that allows for more complex disk approximations, we examine the effects that disk thickness may have on the reflection spectrum. Assuming a lamppost corona, we find that finite disk thickness can have a variety of effects on the reflection spectrum, including a truncation of the blue wing (from self-shadowing of the accretion disk) and an enhancement of the red wing (from the irradiation of the central “eye wall” of the inner disk). We deduce the systematic errors on black hole spin and height that may result from neglecting these effects.

Effect of bioactive borate glass microstructure on bone regeneration, angiogenesis, and hydroxyapatite conversion in a rat calvarial defect model.

PubMed

Bi, Lianxiang; Rahaman, Mohamed N; Day, Delbert E; Brown, Zackary; Samujh, Christopher; Liu, Xin; Mohammadkhah, Ali; Dusevich, Vladimir; Eick, J David; Bonewald, Lynda F

2013-08-01

Borate bioactive glasses are biocompatible and enhance new bone formation, but the effect of their microstructure on bone regeneration has received little attention. In this study scaffolds of borate bioactive glass (1393B3) with three different microstructures (trabecular, fibrous, and oriented) were compared for their capacity to regenerate bone in a rat calvarial defect model. 12weeks post-implantation the amount of new bone, mineralization, and blood vessel area in the scaffolds were evaluated using histomorphometric analysis and scanning electron microscopy. The amount of new bone formed was 33%, 23%, and 15%, respectively, of the total defect area for the trabecular, oriented, and fibrous microstructures. In comparison, the percent new bone formed in implants composed of silicate 45S5 bioactive glass particles (250-300μm) was 19%. Doping the borate glass with copper (0.4 wt.% CuO) had little effect on bone regeneration in the trabecular and oriented scaffolds, but significantly enhanced bone regeneration in the fibrous scaffolds (from 15 to 33%). The scaffolds were completely converted to hydroxyapatite within the 12week implantation. The amount of hydroxyapatite formed, 22%, 35%, and 48%, respectively, for the trabecular, oriented, and fibrous scaffolds, increased with increasing volume fraction of glass in the as-fabricated scaffold. Blood vessels infiltrated into all the scaffolds, but the trabecular scaffolds had a higher average blood vessel area compared with the oriented and fibrous scaffolds. While all three scaffold microstructures were effective in supporting bone regeneration, the trabecular scaffolds supported more bone formation and may be more promising in bone repair. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Clinical Use of Deferoxamine in Distraction Osteogenesis of Irradiated Bone

PubMed Central

Momeni, Arash; Rapp, Scott; Donneys, Alexis; Buchman, Steven R.; Wan, Derrick C.

2016-01-01

The deleterious effects of radiotherapy, including hypovascularity and hypocellularity, have made distraction of irradiated bones challenging. Animal studies, however, have demonstrated adjunctive measures such as the administration of deferoxamine to significantly improve bone regeneration across irradiated distraction gaps. In this report, we demonstrate, for the first time, enhanced bone formation following deferoxamine application in a patient following distraction of a previously irradiated maxilla. CT imaging of the pterygomaxillary buttress on the side of administration revealed significantly increased bone area and density relative to the contralateral buttress. This is the first presentation of clinical deferoxamine use to promote bone formation following irradiated bone distraction and highlights the promise for this adjunctive measure to make outcomes after distraction of irradiated bone more reliable. PMID:27171947

Growth Hormone and Craniofacial Tissues. An update

PubMed Central

Litsas, George

2015-01-01

Growth hormone is an important regulator of bone homeostasis. In childhood, it determines the longitudinal bone growth, skeletal maturation, and acquisition of bone mass. In adulthood, it is necessary to maintain bone mass throughout life. Although an association between craniofacial and somatic development has been clearly established, craniofacial growth involves complex interactions of genes, hormones and environment. Moreover, as an anabolic hormone seems to have an important role in the regulation of bone remodeling, muscle enhancement and tooth development. In this paper the influence of growth hormone on oral tissues is reviewed. PMID:25674165

Massive star formation by accretion. II. Rotation: how to circumvent the angular momentum barrier?

NASA Astrophysics Data System (ADS)

Haemmerlé, L.; Eggenberger, P.; Meynet, G.; Maeder, A.; Charbonnel, C.; Klessen, R. S.

2017-06-01

Context. Rotation plays a key role in the star-formation process, from pre-stellar cores to pre-main-sequence (PMS) objects. Understanding the formation of massive stars requires taking into account the accretion of angular momentum during their PMS phase. Aims: We study the PMS evolution of objects destined to become massive stars by accretion, focusing on the links between the physical conditions of the environment and the rotational properties of young stars. In particular, we look at the physical conditions that allow the production of massive stars by accretion. Methods: We present PMS models computed with a new version of the Geneva Stellar Evolution code self-consistently including accretion and rotation according to various accretion scenarios for mass and angular momentum. We describe the internal distribution of angular momentum in PMS stars accreting at high rates and we show how the various physical conditions impact their internal structures, evolutionary tracks, and rotation velocities during the PMS and the early main sequence. Results: We find that the smooth angular momentum accretion considered in previous studies leads to an angular momentum barrier and does not allow the formation of massive stars by accretion. A braking mechanism is needed in order to circumvent this angular momentum barrier. This mechanism has to be efficient enough to remove more than two thirds of the angular momentum from the inner accretion disc. Due to the weak efficiency of angular momentum transport by shear instability and meridional circulation during the accretion phase, the internal rotation profiles of accreting stars reflect essentially the angular momentum accretion history. As a consequence, careful choice of the angular momentum accretion history allows circumvention of any limitation in mass and velocity, and production of stars of any mass and velocity compatible with structure equations.

Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis.

PubMed

Park, Shin-Young; Kim, Kyoung-Hwa; Gwak, Eun-Hye; Rhee, Sang-Hoon; Lee, Jeong-Cheol; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2015-01-01

Peri-implantitis is a chronic inflammatory process with advanced bone loss and impaired healing potential. For peri-implantitis treatment, tissue engineering can be applied to enhance bone regeneration of peri-implant defects. This study aimed to evaluate ex vivo bone morphogenetic protein 2 (BMP2) gene delivery using canine periodontal ligament stem cells (PDLSCs) for regeneration of peri-implantitis defects. Canine PDLSCs were transduced with adenoviral vectors containing BMP2 (BMP2/PDLSCs). After peri-implantitis was induced by ligature placement in six beagle dogs, regenerative procedures were performed; hydroxyapatite (HA) particles and collagen gel with autologous canine PDLSCs (PDLSC group) or BMP2/PDLSCs (BMP/PDLSC group) or without cells (control group) were grafted into the defects and covered by an absorbable membrane. Three months later, the animals were sacrificed. In vitro, BMP2/PDLSCs showed similar levels of stem cell properties to PDLSCs, such as colony-forming efficiency and expression of MSC markers STRO-1 and CD 146. BMP2/PDLSCs produced BMP-2 until day 21 at a concentration of 4-8 ng/mL. In vivo, the BMP2/PDLSC group showed significantly more new bone formation and re-osseointegration in peri-implantitis defects compared to the other groups. In conclusion, ex vivo BMP2 gene delivery using PDLSCs enhanced new bone formation and re-osseointegration in peri-implantitis defects. © 2014 Wiley Periodicals, Inc.

Functional regeneration of ligament-bone interface using a triphasic silk-based graft.

PubMed

Li, Hongguo; Fan, Jiabing; Sun, Liguo; Liu, Xincheng; Cheng, Pengzhen; Fan, Hongbin

2016-11-01

The biodegradable silk-based scaffold with unique mechanical property and biocompatibility represents a favorable ligamentous graft for tissue-engineering anterior cruciate ligament (ACL) reconstruction. However, the low efficiency of ligament-bone interface restoration barriers the isotropic silk graft to common ACL therapeutics. To enhance the regeneration of the silk-mediated interface, we developed a specialized stratification approach implementing a sequential modification on isotropic silk to constitute a triphasic silk-based graft in which three regions respectively referring to ligament, cartilage and bone layers of interface were divided, followed by respective biomaterial coating. Furthermore, three types of cells including bone marrow mesenchymal stem cells (BMSCs), chondrocytes and osteoblasts were respectively seeded on the ligament, cartilage and bone region of the triphasic silk graft, and the cell/scaffold complex was rolled up as a multilayered graft mimicking the stratified structure of native ligament-bone interface. In vitro, the trilineage cells loaded on the triphasic silk scaffold revealed a high proliferative capacity as well as enhanced differentiation ability into their corresponding cell lineage. 24 weeks postoperatively after the construct was implanted to repair the ACL defect in rabbit model, the silk-based ligamentous graft exhibited the enhancement of osseointegration detected by a robust pullout force and formation of three-layered structure along with conspicuously corresponding matrix deposition via micro-CT and histological analysis. These findings potentially broaden the application of silk-based ligamentous graft for ACL reconstruction and further large animal study. Copyright © 2016 Elsevier Ltd. All rights reserved.

CSI 2264: Characterizing Accretion-burst Dominated Light Curves for Young Stars in NGC 2264

NASA Astrophysics Data System (ADS)

Stauffer, John; Cody, Ann Marie; Baglin, Annie; Alencar, Silvia; Rebull, Luisa; Hillenbrand, Lynne A.; Venuti, Laura; Turner, Neal J.; Carpenter, John; Plavchan, Peter; Findeisen, Krzysztof; Carey, Sean; Terebey, Susan; Morales-Calderón, María; Bouvier, Jerome; Micela, Giusi; Flaccomio, Ettore; Song, Inseok; Gutermuth, Rob; Hartmann, Lee; Calvet, Nuria; Whitney, Barbara; Barrado, David; Vrba, Frederick J.; Covey, Kevin; Herbst, William; Furesz, Gabor; Aigrain, Suzanne; Favata, Fabio

2014-04-01

Based on more than four weeks of continuous high-cadence photometric monitoring of several hundred members of the young cluster NGC 2264 with two space telescopes, NASA's Spitzer and the CNES CoRoT (Convection, Rotation, and planetary Transits), we provide high-quality, multi-wavelength light curves for young stellar objects whose optical variability is dominated by short-duration flux bursts, which we infer are due to enhanced mass accretion rates. These light curves show many brief—several hours to one day—brightenings at optical and near-infrared wavelengths with amplitudes generally in the range of 5%-50% of the quiescent value. Typically, a dozen or more of these bursts occur in a 30 day period. We demonstrate that stars exhibiting this type of variability have large ultraviolet (UV) excesses and dominate the portion of the u - g versus g - r color-color diagram with the largest UV excesses. These stars also have large Hα equivalent widths, and either centrally peaked, lumpy Hα emission profiles or profiles with blueshifted absorption dips associated with disk or stellar winds. Light curves of this type have been predicted for stars whose accretion is dominated by Rayleigh-Taylor instabilities at the boundary between their magnetosphere and inner circumstellar disk, or where magneto-rotational instabilities modulate the accretion rate from the inner disk. Among the stars with the largest UV excesses or largest Hα equivalent widths, light curves with this type of variability greatly outnumber light curves with relatively smooth sinusoidal variations associated with long-lived hot spots. We provide quantitative statistics for the average duration and strength of the accretion bursts and for the fraction of the accretion luminosity associated with these bursts. Based on data from the Spitzer and CoRoT missions, as well as the Canada-France-Hawaii Telescope (CFHT) MegaCam CCD, and the European Southern Observatory Very Large Telescope, Paranal Chile, under program 088.C-0239. The CoRoT space mission was developed and is operated by the French space agency CNES, with participation of ESA's RSSD and Science Programmes, Austria, Belgium, Brazil, Germany, and Spain. MegaCam is a joint project of CFHT and CEA/DAPNIA, which is operated by the National Research Council (NRC) of Canada, the Institute National des Sciences de l'Univers of the Centre National de la Recherche Scientifique of France, and the University of Hawaii.

High-fat diet enhances and monocyte chemoattractant protein-1 deficiency reduces bone loss in mice with pulmonary metastases of Lewis lung carcinoma

USDA-ARS?s Scientific Manuscript database

Bone is adversely affected by metastasis and metastasis-associated complications. Obesity is a risk factor for both bone and cancer. Adipose tissue is an endocrine organ that produces pro-inflammatory adipokines, such as monocyte chemotactic protein-1 (MCP-1), that contribute to obesity and obesit...

Numerical simulation of ice accretion phenomena on rotor blade of axial blower

NASA Astrophysics Data System (ADS)

Matsuura, Taiki; Suzuki, Masaya; Yamamoto, Makoto; Shishido, Shinichiro; Murooka, Takeshi; Miyagawa, Hiroshi

2012-08-01

Ice accretion is the phenomenon that super-cooled water droplets impinge and accrete on a body. It is well known that ice accretion on blades and airfoils leads to performance degradation and severe accidents. For this reason, experimental investigations have been carried out using flight tests or icing tunnels. However, it is too expensive, dangerous, and difficult to set actual icing conditions. Hence, computational fluid dynamics is useful to predict ice accretion. A rotor blade is one of jet engine components where ice accretes. Therefore, the authors focus on the ice accretion on a rotor blade in this study. Three-dimensional icing phenomena on the rotor blade of a commercial axial blower are computed here, and ice accretion on the rotor blade is numerically investigated.

Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

PubMed

Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

2015-05-01

Autologous bone graft has been regarded as the criterion standard for the repair of alveolar cleft. However, the most prominent issue in alveolar cleft treatment is the high absorption rate of the bone graft. The authors' objective was to investigate the effects of an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture on the repair of dog alveolar cleft. Twenty beagle dogs with unilateral alveolar clefts created by surgery were divided randomly into four groups: group A underwent repair with an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture; group B underwent repair with autologous iliac bone and bone marrow-derived mesenchymal stem cells; group C underwent repair with autologous iliac bone and platelet-rich fibrin; and group D underwent repair with autologous iliac bone as the control. One day and 6 months after transplantation, the transplant volumes and bone mineral density were assessed by quantitative computed tomography. All of the transplants were harvested for hematoxylin and eosin staining 6 months later. Bone marrow-derived mesenchymal stem cells and platelet-rich fibrin transplants formed the greatest amounts of new bone among the four groups. The new bone formed an extensive union with the underlying maxilla in groups A, B, and C. Transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture retained the majority of their initial volume, whereas the transplants in the control group showed the highest absorption rate. Bone mineral density of transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture 6 months later was significantly higher than in the control group (p < 0.05), and was the highest in bone marrow-derived mesenchymal stem cells and platelet-rich fibrin mixed transplants. Hematoxylin and eosin staining showed that the structure of new bones formed the best in group A. Both bone marrow-derived mesenchymal stem cells and platelet-rich fibrin are capable of improving the repair of dog alveolar cleft, and the mixture of them is more potent than each one of them used singly for enhancing new bone regeneration.

LAMP: the long-term accretion monitoring programme of T Tauri stars in Chamaeleon I

NASA Astrophysics Data System (ADS)

Costigan, G.; Scholz, A.; Stelzer, B.; Ray, T.; Vink, J. S.; Mohanty, S.

2012-12-01

We present the results of a variability study of accreting young stellar objects in the Chameleon I star-forming region, based on ˜300 high-resolution optical spectra from the Fibre Large Area Multi-Element Spectrograph (FLAMES) at the European Southern Observatory (ESO) Very Large Telescope (VLT). 25 objects with spectral types from G2-M5.75 were observed 12 times over the course of 15 months. Using the emission lines Hα (6562.81 Å) and Ca II (8662.1 Å) as accretion indicators, we found 10 accreting and 15 non-accreting objects. We derived accretion rates for all accretors in the sample using the Hα equivalent width, Hα 10 per cent width and Ca II (8662.1 Å) equivalent width. We found that the Hα equivalent widths of accretors varied by ˜7-100 Å over the 15-month period. This corresponds to a mean amplitude of variations in the derived accretion rate of ˜0.37 dex. The amplitudes of variations in the derived accretion rate from Ca II equivalent width were ˜0.83 dex and those from Hα 10 per cent width were ˜1.11 dex. Based on the large amplitudes of variations in accretion rate derived from the Hα 10 per cent width with respect to the other diagnostics, we do not consider it to be a reliable accretion rate estimator. Assuming the variations in Hα and Ca II equivalent width accretion rates to be closer to the true value, these suggest that the spread that was found around the accretion rate to stellar-mass relation is not due to the variability of individual objects on time-scales of weeks to ˜1 year. From these variations, we can also infer that the accretion rates are stable within <0.37 dex over time-scales of less than 15 months. A major portion of the accretion variability was found to occur over periods shorter than the shortest time-scales in our observations, 8-25 days, which are comparable with the rotation periods of these young stellar objects. This could be an indication that what we are probing is spatial structure in the accretion flows and it also suggests that observations on time-scales of ˜a couple of weeks are sufficient to limit the total extent of accretion-rate variations in typical young stars. No episodic accretion was observed: all 10 accretors accreted continuously for the entire period of observations and, though they may have undetected low accretion rates, the non-accretors never showed any large changes in their emission that would imply a jump in accretion rate.

LAUNCHING AND QUENCHING OF BLACK HOLE RELATIVISTIC JETS AT LOW ACCRETION RATE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pu, Hung-Yi; Chang, Hsiang-Kuang; Hirotani, Kouichi

2012-10-20

Relativistic jets are launched from black hole (BH) X-ray binaries and active galactic nuclei when the disk accretion rate is below a certain limit (i.e., when the ratio of the accretion rate to the Eddingtion accretion rate, m-dot , is below about 0.01) but quenched when above. We propose a new paradigm to explain this observed coupling between the jet and the accretion disk by investigating the extraction of the rotational energy of a BH when it is surrounded by different types of accretion disk. At low accretion rates (e.g., when m-dot {approx}<0.1), the accretion near the event horizon ismore » quasi-spherical. The accreting plasmas fall onto the event horizon in a wide range of latitudes, breaking down the force-free approximation near the horizon. To incorporate the plasma inertia effect, we consider the magnetohydrodynamical (MHD) extraction of the rotational energy from BHs by the accreting MHD fluid, as described by the MHD Penrose process. It is found that the energy extraction operates, and hence a relativistic jet is launched, preferentially when the accretion disk consists of an outer Shakura-Sunyaev disk (SSD) and an inner advection-dominated accretion flow. When the entire accretion disk type changes into an SSD, the jet is quenched because the plasmas bring more rest-mass energy than what is extracted from the hole electromagnetically to stop the extraction. Several other issues related to observed BH disk-jet couplings, such as why the radio luminosity increases with increasing X-ray luminosity until the radio emission drops, are also explained.« less

The growth and structure of dark matter haloes

NASA Astrophysics Data System (ADS)

Zhao, D. H.; Mo, H. J.; Jing, Y. P.; Börner, G.

2003-02-01

In this paper, we analyse in detail the mass-accretion histories and structural properties of dark haloes in high-resolution N-body simulations. We model the density distribution in individual haloes using the Navarro-Frenk-White (NFW) profile. For a given halo, there is a tight correlation between its inner-scale radius rs and the mass within it, Ms, for all its main progenitors. Using this correlation, one can predict quite well the structural properties of a dark halo at any time in its history from its mass-accretion history, implying that the structure properties and the mass-accretion history are closely correlated. The predicted growing rate of concentration c with time tends to increase with decreasing mass-accretion rate. The build-up of dark haloes in cold dark matter (CDM) models generally consists of an early phase of fast accretion (where the halo mass Mh increases with time much faster than the expansion rate of the Universe) and a late phase of slow accretion (where Mh increases with time approximately as the expansion rate). These two phases are separated at a time when c~ 4 and the typical binding energy of the halo is approximately equal to that of a singular isothermal sphere with the same circular velocity. Haloes in the two accretion phases show systematically different properties, for example, the circular velocity vh increases rapidly with time in the fast accretion phase but remains almost constant in the slow accretion phase, the inner properties of a halo, such as rs and Ms increase rapidly with time in the fast accretion phase but change only slowly in the slow accretion phase, the inner circular velocity vs is approximately equal to vh in the fast accretion phase but is larger in the slow accretion phase. The potential well associated with a halo is built up mainly in the fast accretion phase, while a large amount of mass can be accreted in the slow accretion phase without changing the potential well significantly. We discuss our results in connection with the formation of dark haloes and galaxies in hierarchical models.

Effect of HIP/Ribosomal Protein L29 Deficiency on Mineral Properties of Murine Bones and Teeth

PubMed Central

Sloofman, Laura G.; Verdelis, Kostas; Spevak, Lyudmila; Zayzafoon, Majd; Yamauchi, Mistuo; Opdenaker, Lynn M.; Farach-Carson, Mary C.; Boskey, Adele L.; Kirn-Safran, Catherine B.

2010-01-01

Mice lacking HIP/RPL29, a component of the ribosomal machinery, display increased bone fragility. To understand the effect of sub-efficient protein synthetic rates on mineralized tissue quality, we performed dynamic and static histomorphometry and examined the mineral properties of both bones and teeth in HIP/RPL29 knock-out mice using Fourier transform infrared imaging (FTIRI). While loss of HIP/RPL29 consistently reduced total bone size, decreased mineral apposition rates were not significant, indicating that short stature is not primarily due to impaired osteoblast function. Interestingly, our microspectroscopic studies showed that a significant decrease in collagen crosslinking during maturation of HIP/RPL29-null bone precedes an overall enhancement in the relative extent of mineralization of both trabecular and cortical adult bones. This report provides strong genetic evidence that ribosomal insufficiency induces subtle organic matrix deficiencies which elevates calcification. Consistent with the HIP/RPL29-null bone phenotype, HIP/RPL29-deficient teeth also showed reduced geometric properties accompanied with relative increased mineral densities of both dentin and enamel. Increased mineralization associated with enhanced tissue fragility related to imperfection in organic phase microstructure evokes defects seen in matrix protein-related bone and tooth diseases. Thus, HIP/RPL29 mice constitute a new genetic model for studying the contribution of global protein synthesis in the establishment of organic and inorganic phases in mineral tissues. PMID:20362701

Peptide-incorporated 3D porous alginate scaffolds with enhanced osteogenesis for bone tissue engineering.

PubMed

Luo, Zuyuan; Yang, Yue; Deng, Yi; Sun, Yuhua; Yang, Hongtao; Wei, Shicheng

2016-07-01

Good bioactivity and osteogenesis of three-dimensional porous alginate scaffolds (PAS) are critical for bone tissue engineering. In this work, alginate and bone-forming peptide-1 (BFP-1), derived from bone morphogenetic protein-7 (BMP-7), have been combined together (without carbodiimide chemistry treatment) to develop peptide-incorporated PAS (p-PAS) for promoting bone repairing ability. The mechanical properties and SEM images show no difference between pure PAS and p-PAS. The release kinetics of the labeled peptide with 6-carboxy tetramethyl rhodamine from the PAS matrix suggests that the peptide is released in a relatively sustained manner. In the cell experiment, p-PAS show higher cell adhesion, spreading, proliferation and alkaline phosphatase (ALP) activity than the pristine PAS group, indicating that the BFP-1 released from p-PAS could significantly promote the aggregation and differentiation of osteoblasts, especially at 10μg/mL of trapped peptide concentration (p-PAS-10). Furthermore, p-PAS-10 was implanted into Beagle calvarial defects and bone regeneration was analyzed after 4 weeks. New bone formation was assessed by calcein and Masson's trichrome staining. The data reveal that p-PAS group exhibits significantly enhanced oseto-regenerative capability in vivo. The peptide-modified PAS with promoted bioactivity and osteogenic differentiation in vitro as well as bone formation ability in vivo could be promising tissue engineering materials for repairing and regeneration of bone defects. Copyright © 2016 Elsevier B.V. All rights reserved.

Improvement of Bone Healing by Neutralization of microRNA-335-5p, but not by Neutralization of microRNA-92A in Bone Marrow Mononuclear Cells Transplanted into a Large Femur Defect of the Rat.

PubMed

Janko, Maren; Dietz, Konstantin; Rachor, Julia; Sahm, Julian; Schroder, Katrin; Schaible, Alexander; Nau, Christoph; Seebach, Caroline; Marzi, Ingo; Henrich, Dirk

2018-04-23

Transplanted bone marrow mononuclear cells (BMC) support the healing of large bone defects. Neutralization of microRNA (MiR) that negatively affects key processes of the reparative response in BMC might help to further improve the beneficial effect of transplanted BMC in bone healing. Hence, the aim of this study was to evaluate if the neutralization of MiR-92A (vascularization) and MiR-335-5p (osteogenic differentiation) in BMC using specific antiMiRs leads to a further improvement of the BMC-supported therapy of large bone defects. BMC transiently transfected with antiMiR- 92A, antiMiR-335, antiMiR-92A, and antiMiR-355 or control antiMiR were seeded on β-TCP (beta-tricalcium phosphate) and placed in a femoral large bone defect (5 mm) in Sprague-Dawley rats. Ultimate load as well as osseous integration of the β-TCP-scaffolds were significantly improved in the antiMiR-335 group compared to the control group after 8 weeks, whereas neutralization of antiMiR-92A lead to an improvement of early vascularization after 1 week, but not to enhanced bone healing after 8 weeks. We demonstrated that the targeted inhibition of MiRs in transplanted BMC is a new approach that enhances BMC-supported bone healing.

Bone geometry, structure and mineral distribution using Dual energy X ray Absorptiometry (DXA)

NASA Technical Reports Server (NTRS)

Whalen, Robert; Cleek, Tammy

1993-01-01

Dual energy x-ray absorptiometry (DXA) is currently the most widely used method of analyzing regional and whole body changes in bone mineral content (BMC) and areal (g/sq cm) bone mineral density (BMD). However, BMC and BMD do not provide direct measures of long bone geometry, structure, or strength nor do regional measurements detect localized changes in other regions of the same bone. The capabilities of DXA can be enhanced significantly by special processing of pixel BMC data which yields cross-sectional geometric and structural information. We have extended this method of analysis in order to develop non-uniform structural beam models of long bones.

Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation.

PubMed

Taipaleenmäki, Hanna; Bjerre Hokland, Lea; Chen, Li; Kauppinen, Sakari; Kassem, Moustapha

2012-03-01

Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, a novel class of regulatory factors termed micro-RNAs (miRNAs) has been identified as playing an important role in the regulation of many aspects of osteoblast biology including proliferation, differentiation, metabolism and apoptosis. Also, preliminary data from animal disease models suggest that targeting miRNAs in bone can be a novel approach to increase bone mass. This review highlights the current knowledge of miRNA biology and their role in bone formation and discusses their potential use in future therapeutic applications for metabolic bone diseases.

Different bone regeneration patterns in periimplant circumferential gap defects grafted with two types of osteoconductive biomaterial.

PubMed

Lee, Jung-Seok; Sohn, Joo-Yeon; Lim, Hyun-Chang; Jung, Ui-Won; Choi, Seong-Ho

2016-08-01

This study aimed to determine healing patterns in periimplant gap defect grafted with demineralized bovine bone mineral (DBBM) and porous titanium granules (PTG), which are known to induce a minimal tissue reaction and to undergo minimal biodegradation in healing process. Experiments were performed using a standardized periimplant gap-defect model in dogs with two observational periods: 4 and 8 weeks. Circumferential defects were surgically induced around dental implants on unilateral mandibles in five dogs, and collagen barrier membranes were placed over the DBBM and PTG grafts at two experimental sites and over a nongrafted site. Four weeks later, the same procedures were performed on the contralateral mandible, and the animals allowed to heal for a further 4 weeks, after which they were sacrificed and their mandibles with graft/control sites harvested for histologic evaluation. Both types of grafted biomaterials significantly enhanced the defect fill with newly formed bone, but the bone-to-implant contact (BIC) was significantly increased only at sites that had been grafted with DBBM. The two experimental sites exhibited different healing patterns, with new bone formation being observed on the surface of the DBBM particles throughout the defect, while there was no de novo bone formation on the PTG surface, but rather appositional bone growth from the base and lateral walls of the defect. It has been suggested that gap-defect filling with DBBM around dental implants may enhance both BIC and defect fill; however, the present findings show that defect grafting with PTG enhances only defect fill and not BIC. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1202-1209, 2016. © 2015 Wiley Periodicals, Inc.

Studies the alterations of biochemical and mineral contents in bone tissue of mus musculus due to aluminum toxicity and the protective action of desferrioxamine and deferiprone by FTIR, ICP-OES, SEM and XRD techniques.

PubMed

Sivakumar, S; Khatiwada, Chandra Prasad; Sivasubramanian, J

2014-05-21

The present study has attempt to analyze the changes in the biochemical and mineral contents of aluminum intoxicated bone and determine the protective action of desferrioxamine (DFO) and deferiprone (DFP) by using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), inductively coupled plasma optical emission spectroscopy (ICP-OES), and scanning electron microscopy (SEM) techniques for four groups of animals such as control (Group I), aluminum intoxicated (Group II), Al+DFP (Group III) and Al+DFO+DFP (Group IV) treated groups respectively. The FTIR spectra of the aluminum intoxicated bone showed significant alteration in the biochemical constituents. The bands ratio at I1400/I877 significantly decreased from control to aluminum, but enhanced it by Al+DFP to Al+DFO+DFP treated bone tissue for treatments of 16 weeks. This result suggests that DFO and DFP are the carbonate inhibitor, recovered from chronic growth of bone diseases and pathologies. The alteration of proteins profile indicated by Amide I and Amide II, where peak area values decreased from control to aluminum respectively, but enhanced by treated with DFP (p.o.) and DFO+DFP (i.p.) respectively. The XRD analysis showed a decrease in crystallinity due to aluminum toxicity. Further, the Ca, Mg, and P contents of the aluminum exposed bone were less than those of the control group, and enhanced by treatments with DFO and DFP. The concentrations of trace elements were found by ICP-OES. Therefore, present study suggests that due to aluminum toxicity severe loss of bone minerals, decrease in the biochemical constituents and changes in the surface morphology. Copyright © 2014 Elsevier B.V. All rights reserved.

BMP-7 Preserves Surface Integrity of Degradable-ceramic Cranioplasty in a Göttingen Minipig Model

PubMed Central

Schulz, Peter; Klünter, Tim; Deisinger, Ulrike; Diez, Claudius; Waiss, Waltraud; Kirschneck, Christian; Reichert, Torsten E.; Detsch, Rainer

2017-01-01

Background: The aim of the study was to evaluate the integrity of a craniotomy grafted site in a minipig model using different highly porous calcium phosphate ceramic scaffolds either loaded or nonloaded with bone morphogenetic protein-7 (BMP-7). Methods: Four craniotomies with a diameter of 15 mm (critical-size defect) were grafted with different highly porous (92–94 vol%) calcium phosphate ceramics [hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP; a mixture of HA and TCP)] in 10 Göttingen minipigs: (a) group I (n = 5): HA versus BCP; (b) group II (n = 5): TCP versus BCP. One scaffold of each composition was supplied with 250 μg of BMP-7. In vivo computed tomography scan and fluorochrome bone labeling were performed. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, and Giemsa staining histology. Results: BMP-7 significantly enhanced bone formation in TCP (P = 0.047). Slightly enhanced bone formation was observed in BCP (P = 0.059) but not in HA implants. BMP-7 enhanced ceramic degradation in TCP (P = 0.05) and BCP (P = 0.05) implants but not in HA implants. Surface integrity of grafted site was observed in all BMP-7-loaded implants after successful creeping substitution by the newly formed bone. In 9 of 10 HA implants without BMP-7, partial collapse of the implant site was observed. All TCP implants without BMP-7 collapsed. Fluorescent labeling showed bone formation at week 1 in BMP-7-stimulated implants. Conclusions: BMP-7 supports bone formation, ceramic degradation, implant integration, and surface integrity of the grafted site. PMID:28458969

Load-sharing through elastic micro-motion accelerates bone formation and interbody fusion.

PubMed

Ledet, Eric H; Sanders, Glenn P; DiRisio, Darryl J; Glennon, Joseph C

2018-02-13

Achieving a successful spinal fusion requires the proper biological and biomechanical environment. Optimizing load-sharing in the interbody space can enhance bone formation. For anterior cervical discectomy and fusion (ACDF), loading and motion are largely dictated by the stiffness of the plate, which can facilitate a balance between stability and load-sharing. The advantages of load-sharing may be substantial for patients with comorbidities and in multilevel procedures where pseudarthrosis rates are significant. We aimed to evaluate the efficacy of a novel elastically deformable, continuously load-sharing anterior cervical spinal plate for promotion of bone formation and interbody fusion relative to a translationally dynamic plate. An in vivo animal model was used to evaluate the effects of an elastically deformable spinal plate on bone formation and spine fusion. Fourteen goats underwent an ACDF and received either a translationally dynamic or elastically deformable plate. Animals were followed up until 18 weeks and were evaluated by plain x-ray, computed tomography scan, and undecalcified histology to evaluate the rate and quality of bone formation and interbody fusion. Animals treated with the elastically deformable plate demonstrated statistically significantly superior early bone formation relative to the translationally dynamic plate. Trends in the data from 8 to 18 weeks postoperatively suggest that the elastically deformable implant enhanced bony bridging and fusion, but these enhancements were not statistically significant. Load-sharing through elastic micro-motion accelerates bone formation in the challenging goat ACDF model. The elastically deformable implant used in this study may promote early bony bridging and increased rates of fusion, but future studies will be necessary to comprehensively characterize the advantages of load-sharing through micro-motion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of the Interposition of Calcium Phosphate Materials on Tendon-Bone Healing During Repair of Chronic Rotator Cuff Tear.

PubMed

Zhao, Song; Peng, Lingjie; Xie, Guoming; Li, Dingfeng; Zhao, Jinzhong; Ning, Congqin

2014-08-01

The current nature of tendon-bone healing after rotator cuff (RC) repair is still the formation of granulation tissue at the tendon-bone interface rather than the formation of fibrocartilage, which is the crucial structure in native tendon insertion and can be observed after knee ligament reconstruction. The interposition of calcium phosphate materials has been found to be able to enhance tendon-bone healing in knee ligament reconstruction. However, whether the interposition of these kinds of materials can enhance tendon-bone healing or even change the current nature of tendon-bone healing after RC repair still needs to be explored. The interposition of calcium phosphate materials during RC repair would enhance tendon-bone healing or change its current nature of granulation tissue formation into a more favorable process. Controlled laboratory study. A total of 144 male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon, followed by delayed repair after 3 weeks. The animals were allocated into 1 of 3 groups: (1) repair alone, (2) repair with Ca5(PO4)2SiO4 (CPS) bioceramic interposition, or (3) repair with hydroxyapatite (HA) bioceramic interposition at the tendon-bone interface. Animals were sacrificed at 2, 4, or 8 weeks postoperatively, and microcomputed tomography (micro-CT) was used to quantify the new bone formation at the repair site. New fibrocartilage formation and collagen organization at the tendon-bone interface was evaluated by histomorphometric analysis. Biomechanical testing of the supraspinatus tendon-bone complex was performed. Statistical analysis was performed using 1-way analysis of variance. Significance was set at P < .05. The micro-CT analysis demonstrated remarkable osteogenic activity and osteoconductivity to promote new bone formation and ingrowth of CPS and HA bioceramic, with CPS bioceramic showing better results than HA. Histological observations indicated that CPS bioceramic had excellent biocompatibility and biodegradability. At early time points after the RC repair, CPS bioceramic significantly increased the area of fibrocartilage at the tendon-bone interface compared with the control and HA groups. Moreover, CPS and HA bioceramics had significantly improved collagen organization. Biomechanical tests indicated that the CPS and HA groups have greater ultimate load to failure and stiffness than the control group at 4 and 8 weeks, and the CPS specimens exhibited the maximum ultimate load to failure, stiffness, and stress of the healing enthesis. Both CPS and HA bioceramics aid in cell attachment and proliferation and accelerate new bone formation, and CPS bioceramic has a more prominent effect on tendon-to-bone healing. Local application of CPS and HA bioceramic at the tendon-bone interface shows promise in improving healing after rotator cuff tear repair. © 2014 The Author(s).

Accreting CO material onto ONe white dwarfs towards accretion-induced collapse

NASA Astrophysics Data System (ADS)

Wu, Cheng-Yuan; Wang, Bo

2018-03-01

The final outcomes of accreting ONe white dwarfs (ONe WDs) have been studied for several decades, but there are still some issues that are not resolved. Recently, some studies suggested that the deflagration of oxygen would occur for accreting ONe WDs with Chandrasekhar masses. In this paper, we aim to investigate whether ONe WDs can experience accretion-induced collapse (AIC) or explosions when their masses approach the Chandrasekhar limit. Employing the stellar evolution code Modules for Experiments in Stellar Astrophysics (MESA), we simulate the long-term evolution of ONe WDs with accreting CO material. The ONe WDs undergo weak multicycle carbon flashes during the mass-accretion process, leading to mass increase of the WDs. We found that different initial WD masses and mass-accretion rates influence the evolution of central density and temperature. However, the central temperature cannot reach the explosive oxygen ignition temperature due to neutrino cooling. This work implies that the final outcome of accreting ONe WDs is electron-capture induced collapse rather than thermonuclear explosion.

Epigallocatechin Gallate-Modified Gelatin Sponges Treated by Vacuum Heating as a Novel Scaffold for Bone Tissue Engineering.

PubMed

Honda, Yoshitomo; Takeda, Yoshihiro; Li, Peiqi; Huang, Anqi; Sasayama, Satoshi; Hara, Eiki; Uemura, Naoya; Ueda, Mamoru; Hashimoto, Masanori; Arita, Kenji; Matsumoto, Naoyuki; Hashimoto, Yoshiya; Baba, Shunsuke; Tanaka, Tomonari

2018-04-11

Chemical modification of gelatin using epigallocatechin gallate (EGCG) promotes bone formation in vivo. However, further improvements are required to increase the mechanical strength and bone-forming ability of fabricated EGCG-modified gelatin sponges (EGCG-GS) for practical applications in regenerative therapy. In the present study, we investigated whether vacuum heating-induced dehydrothermal cross-linking of EGCG-GS enhances bone formation in critical-sized rat calvarial defects. The bone-forming ability of vacuum-heated EGCG-GS (vhEGCG-GS) and other sponges was evaluated by micro-computed tomography and histological staining. The degradation of sponges was assessed using protein assays, and cell morphology and proliferation were verified by scanning electron microscopy and immunostaining using osteoblastic UMR106 cells in vitro. Four weeks after the implantation of sponges, greater bone formation was detected for vhEGCG-GS than for EGCG-GS or vacuum-heated gelatin sponges (dehydrothermal cross-linked sponges without EGCG). In vitro experiments revealed that the relatively low degradability of vhEGCG-GS supports cell attachment, proliferation, and cell-cell communication on the matrix. These findings suggest that vacuum heating enhanced the bone forming ability of EGCG-GS, possibly via the dehydrothermal cross-linking of EGCG-GS, which provides a scaffold for cells, and by maintaining the pharmacological effect of EGCG.

Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone

PubMed Central

Culpepper, Bonnie K.; Bonvallet, Paul P.; Reddy, Michael S.; Ponnazhagan, Selvarangan; Bellis, Susan L.

2012-01-01

Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments. PMID:23182349

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

PubMed

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling

PubMed Central

Masuda, Tetsuro; Endo, Motoyoshi; Yamamoto, Yutaka; Odagiri, Haruki; Kadomatsu, Tsuyoshi; Nakamura, Takayuki; Tanoue, Hironori; Ito, Hitoshi; Yugami, Masaki; Miyata, Keishi; Morinaga, Jun; Horiguchi, Haruki; Motokawa, Ikuyo; Terada, Kazutoyo; Morioka, Masaki Suimye; Manabe, Ichiro; Iwase, Hirotaka; Mizuta, Hiroshi; Oike, Yuichi

2015-01-01

Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer. PMID:25773070

Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation

PubMed Central

Yu, Weilin; Sun, Tuan-Wei; Qi, Chao; Ding, Zhenyu; Zhao, Huakun; Zhao, Shichang; Shi, Zhongmin; Zhu, Ying-Jie; Chen, Daoyun; He, Yaohua

2017-01-01

Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100–300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration. PMID:28392688

Participation in ball sports may represent a prehabilitation strategy to prevent future stress fractures and promote bone health in young athletes.

PubMed

Tenforde, Adam Sebastian; Sainani, Kristin Lynn; Carter Sayres, Lauren; Milgrom, Charles; Fredericson, Michael

2015-02-01

Sports participation has many benefits for the young athlete, including improved bone health. However, a subset of athletes may attain suboptimal bone health and be at increased risk for stress fractures. This risk is greater for female than for male athletes. In healthy children, high-impact physical activity has been shown to improve bone health during growth and development. We offer our perspective on the importance of promoting high-impact, multidirectional loading activities, including ball sports, as a method of enhancing bone quality and fracture prevention based on collective research. Ball sports have been associated with greater bone mineral density and enhanced bone geometric properties compared with participation in repetitive, low-impact sports such as distance running or nonimpact sports such as swimming. Runners and infantry who participated in ball sports during childhood were at decreased risk of future stress fractures. Gender-specific differences, including the coexistence of female athlete triad, may negate the benefits of previous ball sports on fracture prevention. Ball sports involve multidirectional loading with high ground reaction forces that may result in stiffer and more fracture-resistant bones. Encouraging young athletes to participate in ball sports may optimize bone health in the setting of adequate nutrition and in female athletes, eumenorrhea. Future research to determine timing, frequency, and type of loading activity could result in a primary prevention program for stress fracture injuries and improved life-long bone health. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model

PubMed Central

Aro, Hannu T; Kulkova, Julia; Moritz, Niko; Kähkönen, Esa; Mattila, Riina H

2015-01-01

Background and purpose — Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984). Methods — ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry. Results — Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%). Interpretation — This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs. PMID:26198725

Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation.

PubMed

Yu, Weilin; Sun, Tuan-Wei; Qi, Chao; Ding, Zhenyu; Zhao, Huakun; Zhao, Shichang; Shi, Zhongmin; Zhu, Ying-Jie; Chen, Daoyun; He, Yaohua

2017-01-01

Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100-300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration.

Enhanced bone screw fixation with biodegradable bone cement in osteoporotic bone model.

PubMed

Juvonen, Tiina; Koistinen, Arto; Kröger, Heikki; Lappalainen, Reijo

2012-09-27

The purpose of this study was to study the potential of novel biodegradable PCL bone cement to improve bone screw fixation strength in osteoporotic bone. The biomechanical properties of bone cement (ε-polycaprolactone, PCL) and fixation strength were studied using biomechanical tests and bone screws fixed in an osteoporotic bone model. Removal torques and pullout strengths were assessed for cortical, self-tapping, and cancellous screws inserted in the osteoporotic bone model (polyurethane foam blocks with polycarbonate plate) with and without PCL bone cement. Open cell and cellular rigid foam blocks with a density of 0.12 g/cm3 were used in this model. Removal torques were significantly (more than six-fold) improved with bone cement for cancellous screws. Furthermore, the bone cement improved pullout strengths three to 12 times over depending on the screw and model material. Biodegradable bone cement turned out to be a very potential material to stabilize screw fixation in osteoporotic bone. The results warrant further research before safe clinical use, especially to clarify clinically relevant factors using real osteoporotic bone under human body conditions and dynamic fatigue testing for long-term performance.

Accretion Discs Around Black Holes: Developement of Theory

NASA Astrophysics Data System (ADS)

Bisnovatyi-Kogan, G. S.

Standard accretion disk theory is formulated which is based on the local heat balance. The energy produced by a turbulent viscous heating is supposed to be emitted to the sides of the disc. Sources of turbulence in the accretion disc are connected with nonlinear hydrodynamic instability, convection, and magnetic field. In standard theory there are two branches of solution, optically thick, and optically thin. Advection in accretion disks is described by the differential equations what makes the theory nonlocal. Low-luminous optically thin accretion disc model with advection at some suggestions may become advectively dominated, carrying almost all the energy inside the black hole. The proper account of magnetic filed in the process of accretion limits the energy advected into a black hole, efficiency of accretion should exceed ˜ 1/4 of the standard accretion disk model efficiency.

Accretion Rates for T Tauri Stars Using Nearly Simultaneous Ultraviolet and Optical Spectra

NASA Astrophysics Data System (ADS)

Ingleby, Laura; Calvet, Nuria; Herczeg, Gregory; Blaty, Alex; Walter, Frederick; Ardila, David; Alexander, Richard; Edwards, Suzan; Espaillat, Catherine; Gregory, Scott G.; Hillenbrand, Lynne; Brown, Alexander

2013-04-01

We analyze the accretion properties of 21 low-mass T Tauri stars using a data set of contemporaneous near-UV (NUV) through optical observations obtained with the Hubble Space Telescope Imaging Spectrograph and the ground-based Small and Medium Aperture Research Telescope System, a unique data set because of the nearly simultaneous broad wavelength coverage. Our data set includes accreting T Tauri stars in Taurus, Chamaeleon I, η Chamaeleon, and the TW Hydra Association. For each source we calculate the accretion rate (\\dot{M}) by fitting the NUV and optical excesses above the photosphere, produced in the accretion shock, introducing multiple accretion components characterized by a range in energy flux (or density) for the first time. This treatment is motivated by models of the magnetospheric geometry and accretion footprints, which predict that high-density, low filling factor accretion spots coexist with low-density, high filling factor spots. By fitting the UV and optical spectra with multiple accretion components, we can explain excesses which have been observed in the near-IR. Comparing our estimates of \\dot{M} to previous estimates, we find some discrepancies; however, they may be accounted for when considering assumptions for the amount of extinction and variability in optical spectra. Therefore, we confirm many previous estimates of the accretion rate. Finally, we measure emission line luminosities from the same spectra used for the \\dot{M} estimates, to produce correlations between accretion indicators (Hβ, Ca II K, C II], and Mg II) and accretion properties obtained simultaneously.

Binder-jetting 3D printing and alloy development of new biodegradable Fe-Mn-Ca/Mg alloys.

PubMed

Hong, Daeho; Chou, Da-Tren; Velikokhatnyi, Oleg I; Roy, Abhijit; Lee, Boeun; Swink, Isaac; Issaev, Ilona; Kuhn, Howard A; Kumta, Prashant N

2016-11-01

3D printing of various biomaterials including titanium and stainless steel has been studied for treating patients with cranio-maxillofacial bone defect. The potential long term complications with use of inert biometals have opened the opportunities for use of biodegradable metals in the clinical arena. The authors previously reported that binder-jet 3D printing technique enhanced the degradation rates of biodegradable Fe-Mn alloy by creating engineered micropores rendering the system attractive as biodegradable implantable devices. In the present study, the authors employed CALPHAD modeling to systematically study and modify the Fe-Mn alloy composition to achieve enhanced degradation rates. Accordingly, Ca and Mg addition to Fe-35wt% Mn solid solution predicted increase in degradation rates. In order to validate the CALPHAD results, Fe - (35-y)wt% Mn - ywt% X (X=Ca, Mg, and y=0, 1, 2) were synthesized by using high energy mechanical alloying (HEMA). Sintered pellets of Fe-Mn-Ca and Fe-Mn-Mg were then subjected to potentiodynamic polarization (PDP) and live/dead cell viability tests. Sintered pellets of Fe-Mn, Fe-Mn-Ca, and Fe-Mn-Mg also exhibited MC3T3 murine pre-osteoblast cells viability in the live/dead assay results. Fe-Mn and Fe-Mn-1Ca were thus accordingly selected for 3D printing and the results further confirmed enhanced degradation of Ca addition to 3D printed constructs validating the theoretical and alloy development studies. Live/dead and MTT cell viability results also confirmed good cytocompatibility of the 3D-printed Fe-Mn and Fe-Mn-1Ca constructs. Bone grafting is widely used for the treatment of cranio-maxillofacial bone injuries. 3D printing of biodegradable Fe alloy is anticipated to be advantageous over current bone grafting techniques. 3D printing offers the fabrication of precise and tailored bone grafts to fit the patient specific bone defect needs. Biodegradable Fe alloy is a good candidate for 3D printing synthetic grafts to regenerate bone tissue without eliciting complications. CALPHAD theoretical models were used to develop new Fe-Mn-Ca/Mg alloys to enhance the degradation rates of traditional Fe-Mn alloys. In vitro experimental results also showed enhanced degradation rates and good cytocompatibility of sintered Fe-Mn-Ca/Mg compacts. 3D printing of Fe-Mn and Fe-Mn-1Ca alloys further demonstrated their feasibility as potentially viable bone grafts for the future. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Elemental Compositions of Extrasolar Planetesimals

NASA Astrophysics Data System (ADS)

Xu, Siyi; Jura, M.

2014-01-01

The composition of extrasolar rocky planets is essential for understanding the formation and evolution of these alien worlds. Studying externally-polluted white dwarfs provides the only method to directly measure the elemental compositions of extrasolar planetesimals, the building blocks of planets. The standard model is that some planetesimals can survive to the white dwarf phase, get perturbed, enter into the tidal radius of the white dwarf and get accreted, polluting its pure hydrogen or helium atmosphere. We have been performing high-resolution spectroscopic observations on a number of polluted white dwarfs to measure the bulk compositions of the accreted objects. To have a full picture of the abundance pattern, we gathered data from both Keck/HIRES and HST/COS. I will present the analysis for one of the most interesting objects -- G29-38. It is the first white dwarf identified with an infrared excess from debris of pulverized planetesimals and among the very first identified polluted hydrogen atmosphere white dwarfs. Our analysis indicates that the accreted extrasolar planetesimal is enhanced in refractory elements and depleted in volatile elements. A detailed comparison with solar system objects show that the observed composition can be best interpreted as a blend of chondritic object with some refractory-rich material, a result from post-nebular processing. When all polluted white dwarfs are viewed as an ensemble, we find that the elemental compositions of accreted extrasolar planetesimals resemble to those of solar system objects to zeroth order. (i) The big four elements, O, Fe, Mg and Si are also dominant. Objects with exotic compositions, e.g. diamond planets and refractory-dominated planets, are yet to be found. (ii) Volatiles, such as carbon and water, are only trace constituents. In terms of bulk composition, solar system objects are essentially normal.

THE DOMINANCE OF METAL-RICH STREAMS IN STELLAR HALOS: A COMPARISON BETWEEN SUBSTRUCTURE IN M31 AND {lambda}CDM MODELS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbert, Karoline M.; Font, Andreea S.; Johnston, Kathryn V.

2009-08-10

Extensive photometric and spectroscopic surveys of the Andromeda galaxy (M31) have discovered tidal debris features throughout M31's stellar halo. We present stellar kinematics and metallicities in fields with identified substructure from our on-going SPLASH survey of M31 red giant branch stars with the DEIMOS spectrograph on the Keck II 10 m telescope. Radial velocity criteria are used to isolate members of the kinematically cold substructures. The substructures are shown to be metal-rich relative to the rest of the dynamically hot stellar population in the fields in which they are found. We calculate the mean metallicity and average surface brightness ofmore » the various kinematical components in each field, and show that, on average, higher surface brightness features tend to be more metal-rich than lower surface brightness features. Simulations of stellar halo formation via accretion in a cosmological context are used to illustrate that the observed trend can be explained as a natural consequence of the observed dwarf galaxy mass-metallicity relation. A significant spread in metallicity at a given surface brightness is seen in the data; we show that this is due to time effects, namely, the variation in the time since accretion of the tidal streams' progenitor onto the host halo. We show that in this theoretical framework a relationship between the alpha-enhancement and surface brightness of tidal streams is expected, which arises from the varying times of accretion of the progenitor satellites onto the host halo. Thus, measurements of the alpha-enrichment, metallicity, and surface brightness of tidal debris can be used to reconstruct the luminosity and time of accretion onto the host halo of the progenitors of tidal streams.« less

DISSECTING THE POWER SOURCES OF LOW-LUMINOSITY EMISSION-LINE GALAXY NUCLEI VIA COMPARISON OF HST-STIS AND GROUND-BASED SPECTRA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Constantin, Anca; Castillo, Christopher A.; Shields, Joseph C.

Using a sample of ∼100 nearby line-emitting galaxy nuclei, we have built the currently definitive atlas of spectroscopic measurements of Hα and neighboring emission lines at subarcsecond scales. We employ these data in a quantitative comparison of the nebular emission in Hubble Space Telescope (HST) and ground-based apertures, which offer an order-of-magnitude difference in contrast, and provide new statistical constraints on the degree to which transition objects and low-ionization nuclear emission-line regions (LINERs) are powered by an accreting black hole at ≲10 pc. We show that while the small-aperture observations clearly resolve the nebular emission, the aperture dependence in themore » line ratios is generally weak, and this can be explained by gradients in the density of the line-emitting gas: the higher densities in the more nuclear regions potentially flatten the excitation gradients, suppressing the forbidden emission. The transition objects show a threefold increase in the incidence of broad Hα emission in the high-resolution data, as well as the strongest density gradients, supporting the composite model for these systems as accreting sources surrounded by star-forming activity. The narrow-line LINERs appear to be the weaker counterparts of the Type 1 LINERs, where the low accretion rates cause the disappearance of the broad-line component. The enhanced sensitivity of the HST observations reveals a 30% increase in the incidence of accretion-powered systems at z ≈ 0. A comparison of the strength of the broad-line emission detected at different epochs implies potential broad-line variability on a decade-long timescale, with at least a factor of three in amplitude.« less

Monitoring the coastline change of Hatiya Island in Bangladesh using remote sensing techniques

NASA Astrophysics Data System (ADS)

Ghosh, Manoj Kumer; Kumar, Lalit; Roy, Chandan

2015-03-01

A large percentage of the world's population is concentrated along the coastal zones. These environmentally sensitive areas are under intense pressure from natural processes such as erosion, accretion and natural disasters as well as anthropogenic processes such as urban growth, resource development and pollution. These threats have made the coastal zone a priority for coastline monitoring programs and sustainable coastal management. This research utilizes integrated techniques of remote sensing and geographic information system (GIS) to monitor coastline changes from 1989 to 2010 at Hatiya Island, Bangladesh. In this study, satellite images from Thematic Mapper (TM) and Enhanced Thematic Mapper (ETM) were used to quantify the spatio-temporal changes that took place in the coastal zone of Hatiya Island during the specified period. The modified normalized difference water index (MNDWI) algorithm was applied to TM (1989 and 2010) and ETM (2000) images to discriminate the land-water interface and the on-screen digitizing approach was used over the MNDWI images of 1989, 2000 and 2010 for coastline extraction. Afterwards, the extent of changes in the coastline was estimated through overlaying the digitized maps of Hatiya Island of all three years. Coastline positions were highlighted to infer the erosion/accretion sectors along the coast, and the coastline changes were calculated. The results showed that erosion was severe in the northern and western parts of the island, whereas the southern and eastern parts of the island gained land through sedimentation. Over the study period (1989-2010), this offshore island witnessed the erosion of 6476 hectares. In contrast it experienced an accretion of 9916 hectares. These erosion and accretion processes played an active role in the changes of coastline during the study period.

Enhanced excitability of small dorsal root ganglion neurons in rats with bone cancer pain

PubMed Central

2012-01-01

Background Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the development of bone cancer pain are largely unknown. The aim of this study was to determine whether enhanced excitability of primary sensory neurons contributed to peripheral sensitization and tumor-induced hyperalgesia during cancer condition. In this study, using techniques of whole-cell patch-clamp recording associated with immunofluorescent staining, single-cell reverse-transcriptase PCR and behavioral test, we investigated whether the intrinsic membrane properties and the excitability of small-sized dorsal root ganglion (DRG) neurons altered in a rat model of bone cancer pain, and whether suppression of DRG neurons activity inhibited the bone cancer-induced pain. Results Our present study showed that implantation of MRMT-1 tumor cells into the tibial canal in rats produced significant mechanical and thermal hyperalgesia in the ipsilateral hind paw. Moreover, implantation of tumor cells provoked spontaneous discharges and tonic excitatory discharges evoked by a depolarizing current pulse in small-sized DRG neurons. In line with these findings, alterations in intrinsic membrane properties that reflect the enhanced neuronal excitability were observed in small DRG neurons in bone cancer rats, of which including: 1) depolarized resting membrane potential (RMP); 2) decreased input resistance (Rin); 3) a marked reduction in current threshold (CT) and voltage threshold (TP) of action potential (AP); 4) a dramatic decrease in amplitude, overshot, and duration of evoked action potentials as well as in amplitude and duration of afterhyperpolarization (AHP); and 5) a significant increase in the firing frequency of evoked action potentials. Here, the decreased AP threshold and increased firing frequency of evoked action potentials implicate the occurrence of hyperexcitability in small-sized DRG neurons in bone cancer rats. In addiotion, immunofluorescent staining and single-cell reverse-transcriptase PCR revealed that in isolated small DRG neurons, most neurons were IB4-positive, or expressed TRPV1 or CGRP, indicating that most recorded small DRG neurons were nociceptive neurons. Finally, using in vivo behavioral test, we found that blockade of DRG neurons activity by TTX inhibited the tumor-evoked mechanical allodynia and thermal hyperalgesia in bone cancer rats, implicating that the enhanced excitability of primary sensory neurons underlied the development of bone cancer pain. Conclusions Our present results suggest that implantation of tumor cells into the tibial canal in rats induces an enhanced excitability of small-sized DRG neurons that is probably as results of alterations in intrinsic electrogenic properties of these neurons. Therefore, alterations in intrinsic membrane properties associated with the hyperexcitability of primary sensory neurons likely contribute to the peripheral sensitization and tumor-induced hyperalgesia under cancer condition. PMID:22472208

Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/β-catenin signaling pathway

PubMed Central

Zhang, Wei; Xue, Deting; Yin, Houfa; Wang, Shengdong; Li, Chao; Chen, Erman; Hu, Dongcai; Tao, Yiqing; Yu, Jiawei; Zheng, Qiang; Gao, Xiang; Pan, Zhijun

2016-01-01

HSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Moreover, it upregulated β-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/β-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/β-catenin. PMID:27279016

Characteristics of transonic spherical symmetric accretion flow in Schwarzschild-de Sitter and Schwarzschild anti-de Sitter backgrounds, in pseudo-general relativistic paradigm

NASA Astrophysics Data System (ADS)

Ghosh, Shubhrangshu; Banik, Prabir

2015-07-01

In this paper, we present a complete work on steady state spherically symmetric Bondi type accretion flow in the presence of cosmological constant (Λ) in both Schwarzschild-de Sitter (SDS) and Schwarzschild anti-de Sitter (SADS) backgrounds considering an isolated supermassive black hole (SMBH), with the inclusion of a simple radiative transfer scheme, in the pseudo-general relativistic paradigm. We do an extensive analysis on the transonic behavior of the Bondi type accretion flow onto the cosmological BHs including a complete analysis of the global parameter space and the stability of flow, and do a complete study of the global family of solutions for a generic polytropic flow. Bondi type accretion flow in SADS background renders multiplicity in its transonic behavior with inner "saddle" type and outer "center" type sonic points, with the transonic solutions forming closed loops or contours. There is always a limiting value for ∣Λ∣ up to which we obtain valid stationary transonic solutions, which correspond to both SDS and SADS geometries; this limiting value moderately increases with the increasing radiative efficiency of the flow, especially correspond to Bondi type accretion flow in SADS background. Repulsive Λ suppresses the Bondi accretion rate by an order of magnitude for relativistic Bondi type accretion flow for a certain range in temperature, and with a marginal increase in the Bondi accretion rate if the corresponding accretion flow occurs in SADS background. However, for a strongly radiative Bondi type accretion flow with high mass accretion rate, the presence of cosmological constant do not much influence the corresponding Bondi accretion rate of the flow. Our analysis show that the relic cosmological constant has a substantial effect on Bondi type accretion flow onto isolated SMBHs and their transonic solutions beyond length-scale of kiloparsecs, especially if the Bondi type accretion occurs onto the host supergiant ellipticals or central dominant (CD) galaxies directly from ambient intercluster medium (ICM). However, for high mass accretion rate, the influence of cosmological constant on Bondi accretion dynamics, generically, diminishes. As active galactic nuclei (AGN)/ICM feedback can be advertently linked to Bondi type spherical accretion, any proper modeling of AGN feedback or megaparsecs-scale jet dynamics or accretion flow from ICM onto the central regions of host galaxies should take into account the relevant information of repulsive Λ, especially in context to supergiant elliptical galaxies or CD galaxies present in rich galaxy clusters. This could also explore the feasibility to limit the value of Λ, from the kinematics in local galactic-scales.

Local delivery of parathyroid hormone-related protein-derived peptides coated onto a hydroxyapatite-based implant enhances bone regeneration in old and diabetic rats.

PubMed

Ardura, Juan A; Portal-Núñez, Sergio; Lozano, Daniel; Gutiérrez-Rojas, Irene; Sánchez-Salcedo, Sandra; López-Herradón, Ana; Mulero, Francisca; Villanueva-Peñacarrillo, María L; Vallet-Regí, María; Esbrit, Pedro

2016-08-01

Diabetes mellitus (DM) and aging are associated with bone fragility and increased fracture risk. Both (1-37) N- and (107-111) C-terminal parathyroid hormone-related protein (PTHrP) exhibit osteogenic properties. We here aimed to evaluate and compare the efficacy of either PTHrP (1-37) or PTHrP (107-111) loaded into gelatin-glutaraldehyde-coated hydroxyapatite (HA-Gel) foams to improve bone repair of a transcortical tibial defect in aging rats with or without DM, induced by streptozotocin injection at birth. Diabetic old rats showed bone structural deterioration compared to their age-matched controls. Histological and μ-computerized tomography studies showed incomplete bone repair at 4 weeks after implantation of unloaded Ha-Gel foams in the transcortical tibial defects, mainly in old rats with DM. However, enhanced defect healing, as shown by an increase of bone volume/tissue volume and trabecular and cortical thickness and decreased trabecular separation, occurred in the presence of either PTHrP peptide in the implants in old rats with or without DM. This was accompanied by newly formed bone tissue around the osteointegrated HA-Gel implant and increased gene expression of osteocalcin and vascular endothelial growth factor (bone formation and angiogenic markers, respectively), and decreased expression of Sost gene, a negative regulator of bone formation, in the healing bone area. Our findings suggest that local delivery of PTHrP (1-37) or PTHrP (107-111) from a degradable implant is an attractive strategy to improve bone regeneration in aged and diabetic subjects. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2060-2070, 2016. © 2016 Wiley Periodicals, Inc.

PROLONGED PERFORMANCE OF A HIGH REPETITION LOW FORCE TASK INDUCES BONE ADAPTATION IN YOUNG ADULT RATS, BUT LOSS IN MATURE RATS

PubMed Central

Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

2015-01-01

We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14–18 mo of age) and 14 young adult (2.5–6.5 mo of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

PubMed Central

Yao, Wei; Evan Lay, Yu-An; Kot, Alexander; Liu, Ruiwu; Zhang, Hongliang; Chen, Haiyan; Lam, Kit; Lane, Nancy E.

2017-01-01

Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. PMID:27334693

Effects of fibrinogen concentration on fibrin glue and bone powder scaffolds in bone regeneration.

PubMed

Kim, Beom-Su; Sung, Hark-Mo; You, Hyung-Keun; Lee, Jun

2014-10-01

Fibrin polymers are widely used in the tissue engineering field as biomaterials. Although numerous researchers have studied the fabrication of scaffolds using fibrin glue (FG) and bone powder, the effects of varied fibrinogen content during the fabrication of scaffolds on human mesenchymal stem cells (hMSCs) and bone regeneration remain poorly understood. In this study, we formulated scaffolds using demineralized bone powder and various fibrinogen concentrations and analyzed the microstructure and mechanical properties. Cell proliferation, cell viability, and osteoblast differentiation assays were performed. The ability of the scaffold to enhance bone regeneration was evaluated using a rabbit calvarial defect model. Micro-computed tomography (micro-CT) showed that bone powders were uniformly distributed on the scaffolds, and scanning electron microscopy (SEM) showed that the fibrin networks and flattened fibrin layers connected adjacent bone powder particles. When an 80 mg/mL fibrinogen solution was used to formulate scaffolds, the porosity decreased 41.6 ± 3.6%, while the compressive strength increased 1.16 ± 0.02 Mpa, when compared with the values for the 10 mg/mL fibrinogen solution. Proliferation assays and SEM showed that the scaffolds prepared using higher fibrinogen concentrations supported and enhanced cell adhesion and proliferation. In addition, mRNA expression of alkaline phosphatase and osteocalcin in cells grown on the scaffolds increased with increasing fibrinogen concentration. Micro-CT and histological analysis revealed that newly formed bone was stimulated in the scaffold implantation group. Our results demonstrate that optimization of the fibrinogen content of fibrin glue/bone powder scaffolds will be beneficial for bone tissue engineering. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Segmenting Bone Parts for Bone Age Assessment using Point Distribution Model and Contour Modelling

NASA Astrophysics Data System (ADS)

Kaur, Amandeep; Singh Mann, Kulwinder, Dr.

2018-01-01

Bone age assessment (BAA) is a task performed on radiographs by the pediatricians in hospitals to predict the final adult height, to diagnose growth disorders by monitoring skeletal development. For building an automatic bone age assessment system the step in routine is to do image pre-processing of the bone X-rays so that features row can be constructed. In this research paper, an enhanced point distribution algorithm using contours has been implemented for segmenting bone parts as per well-established procedure of bone age assessment that would be helpful in building feature row and later on; it would be helpful in construction of automatic bone age assessment system. Implementation of the segmentation algorithm shows high degree of accuracy in terms of recall and precision in segmenting bone parts from left hand X-Rays.

The Evolution of Gas Giant Entropy During Formation by Runaway Accretion

NASA Astrophysics Data System (ADS)

Berardo, David; Cumming, Andrew; Marleau, Gabriel-Dominique

2017-01-01

We calculate the evolution of gas giant planets during the runaway gas accretion phase of formation, to understand how the luminosity of young giant planets depends on the accretion conditions. We construct steady-state envelope models, and run time-dependent simulations of accreting planets with the code Modules for Experiments in Stellar Astrophysics. We show that the evolution of the internal entropy depends on the contrast between the internal adiabat and the entropy of the accreted material, parametrized by the shock temperature T 0 and pressure P 0. At low temperatures ({T}0≲ 300-1000 {{K}}, depending on model parameters), the accreted material has a lower entropy than the interior. The convection zone extends to the surface and can drive a high luminosity, leading to rapid cooling and cold starts. For higher temperatures, the accreted material has a higher entropy than the interior, giving a radiative zone that stalls cooling. For {T}0≳ 2000 {{K}}, the surface-interior entropy contrast cannot be accommodated by the radiative envelope, and the accreted matter accumulates with high entropy, forming a hot start. The final state of the planet depends on the shock temperature, accretion rate, and starting entropy at the onset of runaway accretion. Cold starts with L≲ 5× {10}-6 {L}⊙ require low accretion rates and starting entropy, and the temperature of the accreting material needs to be maintained close to the nebula temperature. If instead the temperature is near the value required to radiate the accretion luminosity, 4π {R}2σ {T}04˜ ({GM}\\dot{M}/R), as suggested by previous work on radiative shocks in the context of star formation, gas giant planets form in a hot start with L˜ {10}-4 {L}⊙ .

Elemental Fractionation During Rapid Accretion of the Moon Triggered by a Giant Impact

NASA Technical Reports Server (NTRS)

Abe, Y.; Zahnle, K. J.; Hashimoto, A.

1998-01-01

Recently, Ida et al. made an N-body simulation of lunar accretion from a protolunar disk formed by a giant impact. One of their important conclusions is that the accretion time of the Moon is as short as one month. Such rapid accretion is a necessary consequence of the high surface density of a lunar mass disk accreting just beyond the Roche limit (about 3Re); the Safronov accretion time (a few days) is even shorter. The energy of accretion always exceeds the gravitational binding energy of newly arriving matter. Hence, without an energy sink, the accreting body is thermally unstable. For the Earth and other planets, radiation acts as the sink. However, in such a short accretion time, the Moon cannot radiate the accretional energy. Even radiating at a silicate cloudtop temperature of roughly 2000 K, it would take more than 100 yr to radiatively cool the Moon. The plausible alternative heat sinks are heat capacity, latent heat of vaporization, and thermal escape of the gas to space (i.e., hydrodynamic blowoff). The latter becomes plausible for the Moon because the scale height at 2000 K (about 300 km) is a significant fraction of the lunar radius. The early stages of lunar (or "lunatesimal") growth release relatively little energy and can occur simply by heating the material, especially if the accreting material is originally cold. However, the material is unlikely to be cold, because the disk itself is hot and cooling time is long, while the lunar accretion time iss very short. Therefore, the moon is likely to accrete condensed material just after it condenses. Accordingly, the newly accreted material will be on the verge of vaporization and will have very little heat capacity to spare. The immediate heat sink is the latent heat of vaporization. Most of the vapor will escape from the moon, because the thermal energy in the gas can be used to drive escape. However, vaporization is generally incomplete. the latent heat of vaporization exceeds the energy of accretion. Viewed globally, the accretional energy is about half the energy required to vaporize the entire Moon. Thus to first approximation, half of the Moon-forming material can be vaporized and lost during accretion. During this process, we would expect preferential loss of relatively volatile elements. Escape will retard the rate of accretion. To test these ideas, we computed detailed models of the thermal state of the Moon during accretion. We pay special attention to the structure of the silicate atmosphere and its loss rate by calculating the chemical species at equilibrium. We used the PHEQ program which includes 12 elements (H,O,C,Mg,Si,Fe,Ca, Al, Na,Ti, and N.) and 272 compounds (including ionic compounds). Because of the large heats of vaporization and ionization, the adiabatic atmosphere is nearly isothermal and massive escape is expected. The pressure of the atmosphere is determined by the balance between vaporization of a accreting material and escape. If the accretion time is one month, a 0.3 bar atmosphere is expected. Elemental fractionation depends strongly on the temperature of the accreting material. The initial temperature of the material can be estimated from the condition of gravitational instability in the protolunar disk. As shown by Ida et al, accretion starts when gravitational instability occurs when more than 99% of the material condenses. At this point, all of Ca, Al, Si, Mg, and Fe, and 95% of Na (probably K also), are in condensed phases. If the moon is formed from the accretion of such material, volatile elements such as Na, and K are retained by the moon only early in accretion. At later times, K and Na are lost and a fraction of the MG, Si and Fe is lost. However, refractory elements such as Ca and Al are retained and so achieve a mild degree (factor 2) of superabundance.

Novel daidzein analogs enhance osteogenic activity of bone marrow-derived mesenchymal stem cells and adipose-derived stromal/stem cells through estrogen receptor dependent and independent mechanisms

USDA-ARS?s Scientific Manuscript database

Osteoporosis is a disease characterized by low bone mineral density (BMD) and increased risk of fractures. Studies have demonstrated the use of phytoestrogens, or plant-derived estrogens, such as genistein anddaidzein, to effectively increase osteogenic activity of bone marrow-derived mesenchymal s...

Malignant transformation of a unicameral bone cyst in a cat.

PubMed

Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

2016-04-01

A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis.

Malignant transformation of a unicameral bone cyst in a cat

PubMed Central

Berger, Björn; Brühschwein, Andreas; Eddicks, Lina; Meyer-Lindenberg, Andrea

2016-01-01

A unicameral bone cyst in the proximal humerus of a 3-year-old Norwegian forest cat was diagnosed by dynamic contrast-enhanced magnetic resonance imaging, surgical exploration, and histopathology. Surgical curettage and incorporation of bone cement led to full recovery. An osteosarcoma developed at the surgical site 17 months later. Thoracic radiographs showed pulmonary lesions consistent with metastasis. PMID:27041754

High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

PubMed

Kang, Kyung Lhi; Kim, Eun-Cheol; Park, Joon Bong; Heo, Jung Sun; Choi, Yumi

2016-02-01

Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Controlled delivery of icariin on small intestine submucosa for bone tissue engineering.

PubMed

Li, Mei; Gu, Qiaoqiao; Chen, Mengjie; Zhang, Chi; Chen, Songdi; Zhao, Jiyuan

2017-02-01

Small intestine submucosa (SIS) has been reported as an excellent biomaterial for tissue engineering because of its naturally occurring collagenous extracellular matrix property with growth factors. However, SIS from submucosal layer of intestine provides different microenvironment from bone tissue, which limits its application to bone regeneration. The object of this study was to improve osteoinductivity of SIS by controlled local delivery of icariin (Ic), a potent osteogenic compound. Sustained release of icariin from SIS scaffold was achieved for >30days and the loading of icariin on SIS scaffold was uniform as scanned by SEM. In vitro experiments revealed that expression of osteogenic differentiation markers (Alp, Bsp and Ocn) was increased after treatment of Ic-SIS scaffold, without significant cytotoxicity. In an in vivo mouse calvarial defect model, bone regeneration was enhanced by SIS implantation at 8weeks, compared to control defect. New bone formation was further improved by implantation with Ic-SIS (low and high) at both 4 and 8weeks. The results of this study suggest that SIS scaffold has the potential as an icariin delivery carrier for enhancement of bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

N-AC-l-Leu-PEI-mediated miR-34a delivery improves osteogenic differentiation under orthodontic force.

PubMed

Yu, Wenwen; Zheng, Yi; Yang, Zhujun; Fei, Hongbo; Wang, Yang; Hou, Xu; Sun, Xinhua; Shen, Yuqin

2017-12-15

Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the in vitro and in vivo effects of miR-34a on osteogenic differentiation under orthodontic force using an N -acetyl-L-leucine-modified polyethylenimine ( N -Ac-l-Leu-PEI) carrier. N -Ac-l-Leu-PEI exhibited low cytotoxicity and high miR-34a transfection efficiency in rat bone mineral stem cells and local alveolar bone tissue. After transfection, miR-34a enhanced the osteogenic differentiation of Runx2 and ColI , Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain in vitro . MiR-34a also enhanced alveolar bone remodeling under orthodontic force in vivo , as evidenced by elevated gene and protein expression, upregulated indices of alveolar bone anabolism, and diminished tooth movement. We determined that the mechanism miR-34a in osteogenesis under orthodontic force may be associated with GSK-3β. These results suggested that miR-34a delivered by N -Ac-l-Leu-PEI could be a potential therapeutic target for orthodontic treatment.

PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells

PubMed Central

Gur-Cohen, Shiri; Itkin, Tomer; Chakrabarty, Sagarika; Graf, Claudine; Kollet, Orit; Ludin, Aya; Golan, Karin; Kalinkovich, Alexander; Ledergor, Guy; Wong, Eitan; Niemeyer, Elisabeth; Porat, Ziv; Erez, Ayelet; Sagi, Irit; Esmon, Charles T; Ruf, Wolfram; Lapidot, Tsvee

2016-01-01

Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation-related also control retention of EPCR+ LT-HSCs in the bone marrow and their recruitment to the blood via two different protease activated receptor 1 (PAR1)-mediated pathways. Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to TACE-mediated EPCR shedding, enhanced CXCL12-CXCR4-induced motility, and rapid stem and progenitor cell mobilization. Conversely, bone marrow blood vessels provide a microenvironment enriched with protein C that retain EPCR+ LT-HSCs by limiting NO generation, reducing Cdc42 activity and enhancing VLA4 affinity and adhesion. Inhibition of NO production by activated protein C (aPC)-EPCR-PAR1 signaling reduces progenitor cell egress, increases NOlow bone marrow EPCR+ LT-HSCs retention and protects mice from chemotherapy-induced hematological failure and death. Our study reveals new roles for PAR1 and EPCR that control NO production to balance maintenance and recruitment of bone marrow EPCR+ LT-HSCs with clinical relevance. PMID:26457757

Interactions between MSCs and Immune Cells: Implications for Bone Healing

PubMed Central

Kovach, Tracy K.; Dighe, Abhijit S.; Lobo, Peter I.; Cui, Quanjun

2015-01-01

It is estimated that, of the 7.9 million fractures sustained in the United States each year, 5% to 20% result in delayed or impaired healing requiring therapeutic intervention. Following fracture injury, there is an initial inflammatory response that plays a crucial role in bone healing; however, prolonged inflammation is inhibitory for fracture repair. The precise spatial and temporal impact of immune cells and their cytokines on fracture healing remains obscure. Some cytokines are reported to be proosteogenic while others inhibit bone healing. Cell-based therapy utilizing mesenchymal stromal cells (MSCs) is an attractive option for augmenting the fracture repair process. Osteoprogenitor MSCs not only differentiate into bone, but they also exert modulatory effects on immune cells via a variety of mechanisms. In this paper, we review the current literature on both in vitro and in vivo studies on the role of the immune system in fracture repair, the use of MSCs in the enhancement of fracture healing, and interactions between MSCs and immune cells. Insight into this paradigm can provide valuable clues in identifying cellular and noncellular targets that can potentially be modulated to enhance both natural bone healing and bone repair augmented by the exogenous addition of MSCs. PMID:26000315

Esophageal squamous cell carcinoma with dural and bone marrow metastases.

PubMed

Chen, Yen-Hao; Huang, Cheng-Hua

2014-09-21

Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis. The most common sites of visceral metastasis are the lung, liver and bone, but brain and bone marrow involvement is exceedingly rare. Herein, we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs, dysphagia and body weight loss. Esophageal squamous cell carcinoma with regional lymph node, liver and bone metastases was diagnosed. He underwent concurrent chemoradiotherapy and got a partial response. Four months later, he complained of headache, diplopia and severe hearing impairment in the left ear. There was no evidence for bacterial, fungal, tuberculous infection or neoplastic infiltration. Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull. Dural metastasis was diagnosed and he received whole brain irradiation. In addition, laboratory examination revealed severe thrombocytopenia and leucopenia, and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma. This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases. We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening.

Early Results from NICER Observations of Accreting Neutron Stars

NASA Astrophysics Data System (ADS)

Chakrabarty, Deepto; Ozel, Feryal; Arzoumanian, Zaven; Gendreau, Keith C.; Bult, Peter; Cackett, Ed; Chenevez, Jerome; Fabian, Andy; Guillot, Sebastien; Guver, Tolga; Homan, Jeroen; Keek, Laurens; Lamb, Frederick; Ludlam, Renee; Mahmoodifar, Simin; Markwardt, Craig B.; Miller, Jon M.; Psaltis, Dimitrios; Strohmayer, Tod E.; Wilson-Hodge, Colleen A.; Wolff, Michael T.

2018-01-01

The Neutron Star Interior Composition Explorer (NICER) offers significant new capabilities for the study of accreting neuton stars relative to previous X-ray missions including large effective area, low background, and greatly improved low-energy response. The NICER Burst and Accretion Working Group has designed a 2 Ms observation program to study a number of phenomena in accreting neutron stars including type-I X-ray bursts, superbursts, accretion-powered pulsations, quasi-periodic oscillations, and accretion disk reflection spectra. We present some early results from the first six months of the NICER mission.

Achondroplasia: Development, Pathogenesis, and Therapy

PubMed Central

Ornitz, David M.; Legeai-Mallet, Laurence

2016-01-01

Autosomal dominant mutations in Fibroblast Growth Factor Receptor 3 (FGFR3) cause Achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include Hypochondroplasia (Hch), Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans (SADDAN), and Thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. PMID:27987249

Bone healing in 2016

PubMed Central

Buza, John A.; Einhorn, Thomas

2016-01-01

Summary Delayed fracture healing and nonunion occurs in up to 5–10% of all fractures, and can present a challenging clinical scenario for the treating physician. Methods for the enhancement of skeletal repair may benefit patients that are at risk of, or have experienced, delayed healing or nonunion. These methods can be categorized into either physical stimulation therapies or biological therapies. Physical stimulation therapies include electrical stimulation, low-intensity pulsed ultrasonography, or extracorporeal shock wave therapy. Biological therapies can be further classified into local or systemic therapy based on the method of delivery. Local methods include autologous bone marrow, autologous bone graft, fibroblast growth factor-2, platelet-rich plasma, platelet-derived growth factor, and bone morphogenetic proteins. Systemic therapies include parathyroid hormone and bisphosphonates. This article reviews the current applications and supporting evidence for the use of these therapies in the enhancement of fracture healing. PMID:27920804

Geometric figure–ground cues override standard depth from accretion-deletion

PubMed Central

Tanrıkulu, Ömer Dağlar; Froyen, Vicky; Feldman, Jacob; Singh, Manish

2016-01-01

Accretion-deletion is widely considered a decisive cue to surface depth ordering, with the accreting or deleting surface interpreted as behind an adjoining surface. However, Froyen, Feldman, and Singh (2013) have shown that when accretion-deletion occurs on both sides of a contour, accreting-deleting regions can also be perceived as in front and as self-occluding due to rotation in three dimensions. In this study we ask whether geometric figure–ground cues can override the traditional “depth from accretion-deletion” interpretation even when accretion-deletion takes place only on one side of a contour. We used two tasks: a relative-depth task (front/back), and a motion-classification task (translation/rotation). We conducted two experiments, in which texture in only one set of alternating regions was moving; the other set was static. Contrary to the traditional interpretation of accretion-deletion, the moving convex and symmetric regions were perceived as figural and rotating in three dimensions in roughly half of the trials. In the second experiment, giving different motion directions to the moving regions (thereby weakening motion-based grouping) further weakened the traditional accretion-deletion interpretation. Our results show that the standard “depth from accretion-deletion” interpretation is overridden by static geometric cues to figure–ground. Overall, the results demonstrate a rich interaction between accretion-deletion, figure–ground, and structure from motion that is not captured by existing models of depth from motion. PMID:26982528

Growth of asteroids, planetary embryos, and Kuiper belt objects by chondrule accretion

PubMed Central

Johansen, Anders; Low, Mordecai-Mark Mac; Lacerda, Pedro; Bizzarro, Martin

2015-01-01

Chondrules are millimeter-sized spherules that dominate primitive meteorites (chondrites) originating from the asteroid belt. The incorporation of chondrules into asteroidal bodies must be an important step in planet formation, but the mechanism is not understood. We show that the main growth of asteroids can result from gas drag–assisted accretion of chondrules. The largest planetesimals of a population with a characteristic radius of 100 km undergo runaway accretion of chondrules within ~3 My, forming planetary embryos up to Mars’s size along with smaller asteroids whose size distribution matches that of main belt asteroids. The aerodynamical accretion leads to size sorting of chondrules consistent with chondrites. Accretion of millimeter-sized chondrules and ice particles drives the growth of planetesimals beyond the ice line as well, but the growth time increases above the disc lifetime outside of 25 AU. The contribution of direct planetesimal accretion to the growth of both asteroids and Kuiper belt objects is minor. In contrast, planetesimal accretion and chondrule accretion play more equal roles in the formation of Moon-sized embryos in the terrestrial planet formation region. These embryos are isolated from each other and accrete planetesimals only at a low rate. However, the continued accretion of chondrules destabilizes the oligarchic configuration and leads to the formation of Mars-sized embryos and terrestrial planets by a combination of direct chondrule accretion and giant impacts. PMID:26601169

Growth of asteroids, planetary embryos, and Kuiper belt objects by chondrule accretion

NASA Astrophysics Data System (ADS)

Johansen, Anders; Mac Low, Mordecai-Mark; Lacerda, Pedro; Bizzarro, Martin

2015-04-01

Chondrules are millimeter-sized spherules that dominate primitive meteorites (chondrites) originating from the asteroid belt. The incorporation of chondrules into asteroidal bodies must be an important step in planet formation, but the mechanism is not understood. We show that the main growth of asteroids can result from gas drag-assisted accretion of chondrules. The largest planetesimals of a population with a characteristic radius of 100 km undergo runaway accretion of chondrules within ~3 My, forming planetary embryos up to Mars's size along with smaller asteroids whose size distribution matches that of main belt asteroids. The aerodynamical accretion leads to size sorting of chondrules consistent with chondrites. Accretion of millimeter-sized chondrules and ice particles drives the growth of planetesimals beyond the ice line as well, but the growth time increases above the disc lifetime outside of 25 AU. The contribution of direct planetesimal accretion to the growth of both asteroids and Kuiper belt objects is minor. In contrast, planetesimal accretion and chondrule accretion play more equal roles in the formation of Moon-sized embryos in the terrestrial planet formation region. These embryos are isolated from each other and accrete planetesimals only at a low rate. However, the continued accretion of chondrules destabilizes the oligarchic configuration and leads to the formation of Mars-sized embryos and terrestrial planets by a combination of direct chondrule accretion and giant impacts.

Growth of asteroids, planetary embryos, and Kuiper belt objects by chondrule accretion.

PubMed

Johansen, Anders; Low, Mordecai-Mark Mac; Lacerda, Pedro; Bizzarro, Martin

2015-04-01

Chondrules are millimeter-sized spherules that dominate primitive meteorites (chondrites) originating from the asteroid belt. The incorporation of chondrules into asteroidal bodies must be an important step in planet formation, but the mechanism is not understood. We show that the main growth of asteroids can result from gas drag-assisted accretion of chondrules. The largest planetesimals of a population with a characteristic radius of 100 km undergo runaway accretion of chondrules within ~3 My, forming planetary embryos up to Mars's size along with smaller asteroids whose size distribution matches that of main belt asteroids. The aerodynamical accretion leads to size sorting of chondrules consistent with chondrites. Accretion of millimeter-sized chondrules and ice particles drives the growth of planetesimals beyond the ice line as well, but the growth time increases above the disc lifetime outside of 25 AU. The contribution of direct planetesimal accretion to the growth of both asteroids and Kuiper belt objects is minor. In contrast, planetesimal accretion and chondrule accretion play more equal roles in the formation of Moon-sized embryos in the terrestrial planet formation region. These embryos are isolated from each other and accrete planetesimals only at a low rate. However, the continued accretion of chondrules destabilizes the oligarchic configuration and leads to the formation of Mars-sized embryos and terrestrial planets by a combination of direct chondrule accretion and giant impacts.

OBSERVATIONAL LIMITS ON TYPE 1 ACTIVE GALACTIC NUCLEUS ACCRETION RATE IN COSMOS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trump, Jonathan R.; Impey, Chris D.; Gabor, Jared

2009-07-20

We present black hole masses and accretion rates for 182 Type 1 active galactic nuclei (AGNs) in COSMOS. We estimate masses using the scaling relations for the broad H {beta}, Mg II, and C IV emission lines in the redshift ranges 0.16 < z < 0.88, 1 < z < 2.4, and 2.7 < z < 4.9. We estimate the accretion rate using an Eddington ratio L{sub I}/L{sub Edd} estimated from optical and X-ray data. We find that very few Type 1 AGNs accrete below L{sub I} /L{sub Edd} {approx} 0.01, despite simulations of synthetic spectra which show that themore » survey is sensitive to such Type 1 AGNs. At lower accretion rates the broad-line region may become obscured, diluted, or nonexistent. We find evidence that Type 1 AGNs at higher accretion rates have higher optical luminosities, as more of their emission comes from the cool (optical) accretion disk with respect to shorter wavelengths. We measure a larger range in accretion rate than previous works, suggesting that COSMOS is more efficient at finding low accretion rate Type 1 AGNs. However, the measured range in accretion rate is still comparable to the intrinsic scatter from the scaling relations, suggesting that Type 1 AGNs accrete at a narrow range of Eddington ratio, with L{sub I} /L{sub Edd} {approx} 0.1.« less

Enhanced tendon-to-bone repair through adhesive films.

PubMed

Linderman, Stephen W; Golman, Mikhail; Gardner, Thomas R; Birman, Victor; Levine, William N; Genin, Guy M; Thomopoulos, Stavros

2018-04-01

Tendon-to-bone surgical repairs have unacceptably high failure rates, possibly due to their inability to recreate the load transfer mechanisms of the native enthesis. Instead of distributing load across a wide attachment footprint area, surgical repairs concentrate shear stress on a small number of suture anchor points. This motivates development of technologies that distribute shear stresses away from suture anchors and across the enthesis footprint. Here, we present predictions and proof-of-concept experiments showing that mechanically-optimized adhesive films can mimic the natural load transfer mechanisms of the healthy attachment and increase the load tolerance of a repair. Mechanical optimization, based upon a shear lag model corroborated by a finite element analysis, revealed that adhesives with relatively high strength and low stiffness can, theoretically, strengthen tendon-to-bone repairs by over 10-fold. Lap shear testing using tendon and bone planks validated the mechanical models for a range of adhesive stiffnesses and strengths. Ex vivo human supraspinatus repairs of cadaveric tissues using multipartite adhesives showed substantial increase in strength. Results suggest that adhesive-enhanced repair can improve repair strength, and motivate a search for optimal adhesives. Current surgical techniques for tendon-to-bone repair have unacceptably high failure rates, indicating that the initial repair strength is insufficient to prevent gapping or rupture. In the rotator cuff, repair techniques apply compression over the repair interface to achieve contact healing between tendon and bone, but transfer almost all force in shear across only a few points where sutures puncture the tendon. Therefore, we evaluated the ability of an adhesive film, implanted between tendon and bone, to enhance repair strength and minimize the likelihood of rupture. Mechanical models demonstrated that optimally designed adhesives would improve repair strength by over 10-fold. Experiments using idealized and clinically-relevant repairs validated these models. This work demonstrates an opportunity to dramatically improve tendon-to-bone repair strength using adhesive films with appropriate material properties. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Research on Navy-Related Combat Casualty Care Issues, Navy Operational-Related Injuries and Illnesses and Approaches to Enhance Navy/Marine Corps Personnel Combat Performance.

DTIC Science & Technology

1998-06-01

role of bone morphogenetic protein (BMP) receptors in bone regeneration in periodontal tissues . Tissue samples for these studies are in the accrual...34 Characterization of Bone Morphogenetic Protein Receptors in Oral Tissues " collection of clinical samples will proceed in preparation for assay. • Relative to the...transcribed. • Relative to the project * Characterization of Bone Morphogenetic Protein Receptors in Oral Tissues ", collection of clinical samples is

Enhanced Bone Formation in Segmental Defects with BMP2 in a Biologically Relevant Molecular Context

DTIC Science & Technology

2016-10-16

gun shots . These do not heal on their own once a ‘critical size’ segment of bone is missing. One strategy to induce healing is to use bone-inducing...accelerate BMP2-induced bone formation by presenting the growth factor in a more biologically relevant context. This is based on our observation...that manganese increases the binding of BMP2 to COMP. The next steps are to validate these observations using BMP2:COMP on HA/PLG scaffolds in-vitro

Mapping accretion and its variability in the young open cluster NGC 2264: a study based on u-band photometry

NASA Astrophysics Data System (ADS)

Venuti, L.; Bouvier, J.; Flaccomio, E.; Alencar, S. H. P.; Irwin, J.; Stauffer, J. R.; Cody, A. M.; Teixeira, P. S.; Sousa, A. P.; Micela, G.; Cuillandre, J.-C.; Peres, G.

2014-10-01

Context. The accretion process has a central role in the formation of stars and planets. Aims: We aim at characterizing the accretion properties of several hundred members of the star-forming cluster NGC 2264 (3 Myr). Methods: We performed a deep ugri mapping as well as a simultaneous u-band+r-band monitoring of the star-forming region with CFHT/MegaCam in order to directly probe the accretion process onto the star from UV excess measurements. Photometric properties and stellar parameters are determined homogeneously for about 750 monitored young objects, spanning the mass range ~0.1-2 M⊙. About 40% of the sample are classical (accreting) T Tauri stars, based on various diagnostics (Hα, UV and IR excesses). The remaining non-accreting members define the (photospheric + chromospheric) reference UV emission level over which flux excess is detected and measured. Results: We revise the membership status of cluster members based on UV accretion signatures, and report a new population of 50 classical T Tauri star (CTTS) candidates. A large range of UV excess is measured for the CTTS population, varying from a few times 0.1 to ~3 mag. We convert these values to accretion luminosities and accretion rates, via a phenomenological description of the accretion shock emission. We thus obtain mass accretion rates ranging from a few 10-10 to ~10-7 M⊙/yr. Taking into account a mass-dependent detection threshold for weakly accreting objects, we find a >6σ correlation between mass accretion rate and stellar mass. A power-law fit, properly accounting for censored data (upper limits), yields Ṁacc ∝ M*1.4±0.3. At any given stellar mass, we find a large spread of accretion rates, extending over about 2 orders of magnitude. The monitoring of the UV excess on a timescale of a couple of weeks indicates that its variability typically amounts to 0.5 dex, i.e., much smaller than the observed spread in accretion rates. We suggest that a non-negligible age spread across the star-forming region may effectively contribute to the observed spread in accretion rates at a given mass. In addition, different accretion mechanisms (like, e.g., short-lived accretion bursts vs. more stable funnel-flow accretion) may be associated to different Ṁacc regimes. Conclusions: A huge variety of accretion properties is observed for young stellar objects in the NGC 2264 cluster. While a definite correlation seems to hold between mass accretion rate and stellar mass over the mass range probed here, the origin of the large intrinsic spread observed in mass accretion rates at any given mass remains to be explored. Based on observations obtained with MegaPrime/MegaCam, a joint project of CFHT and CEA/DAPNIA, at the Canada-France-Hawaii Telescope (CFHT) which is operated by the National Research Council (NRC) of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii.Full Tables 2-4 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/570/A82

Design, fabrication and structural optimization of tubular carbon/Kevlar®/PMMA/graphene nanoplate composite for bone fixation prosthesis.

PubMed

Nasiri, F; Ajeli, S; Semnani, D; Jahanshahi, M; Emadi, R

2018-05-02

The present work investigates the mechanical properties of tubular carbon/Kevlar ® composite coated with poly(methyl methacrylate)/graphene nanoplates as used in the internal fixation of bones. Carbon fibers are good candidates for developing high-strength biomaterials and due to better stress transfer and electrical properties, they can enhance tissue formation. In order to improve carbon brittleness, ductile Kevlar ® was added to the composite. The tubular carbon/Kevlar ® composites have been prepared with tailorable braiding technology by changing the fiber pattern and angle in the composite structure and the number of composite layers. Fuzzy analyses are used for optimizing the tailorable parameters of 80 prepared samples and then mechanical properties of selected samples are discussed from the viewpoint of mechanical properties required for a bone fixation device. Experimental results showed that with optimizing braiding parameters the desired composite structure with mechanical properties close to bone properties could be produced. Results showed that carbon/Kevlar ® braid's physical properties, fiber composite distribution and diameter uniformity resulted in matrix uniformity, which enhanced strength and modulus due to better ability for distributing stress on the composite. Finally, as graphene nanoplates demonstrated their potential properties to improve wound healing intended for bone replacement, so reinforcing the PMMA matrix with graphene nanoplates enhanced the composite quality, for use as an implant.

Magnetic flux concentration and zonal flows in magnetorotational instability turbulence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Xue-Ning; Stone, James M., E-mail: xbai@cfa.harvard.edu

2014-11-20

Accretion disks are likely threaded by external vertical magnetic flux, which enhances the level of turbulence via the magnetorotational instability (MRI). Using shearing-box simulations, we find that such external magnetic flux also strongly enhances the amplitude of banded radial density variations known as zonal flows. Moreover, we report that vertical magnetic flux is strongly concentrated toward low-density regions of the zonal flow. Mean vertical magnetic field can be more than doubled in low-density regions, and reduced to nearly zero in high-density regions in some cases. In ideal MHD, the scale on which magnetic flux concentrates can reach a few diskmore » scale heights. In the non-ideal MHD regime with strong ambipolar diffusion, magnetic flux is concentrated into thin axisymmetric shells at some enhanced level, whose size is typically less than half a scale height. We show that magnetic flux concentration is closely related to the fact that the turbulent diffusivity of the MRI turbulence is anisotropic. In addition to a conventional Ohmic-like turbulent resistivity, we find that there is a correlation between the vertical velocity and horizontal magnetic field fluctuations that produces a mean electric field that acts to anti-diffuse the vertical magnetic flux. The anisotropic turbulent diffusivity has analogies to the Hall effect, and may have important implications for magnetic flux transport in accretion disks. The physical origin of magnetic flux concentration may be related to the development of channel flows followed by magnetic reconnection, which acts to decrease the mass-to-flux ratio in localized regions. The association of enhanced zonal flows with magnetic flux concentration may lead to global pressure bumps in protoplanetary disks that helps trap dust particles and facilitates planet formation.« less

Local vs. systemic administration of bisphosphonates in rat cleft bone graft: A comparative study

PubMed Central

Lin, Lawrence; Olson, Jeffrey; Kwon, Taewoo; Bezouglaia, Olga; Tran, Jaime; Hoang, Michael; Bui, Kimberly; Kim, Reuben H.; Tetradis, Sotirios

2018-01-01

A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients. PMID:29304080

Role of Prostaglandin Pathway and Alendronate-Based Carriers to Enhance Statin-induced Bone

PubMed Central

Lee, Yeonju; Liu, Xinming; Nawshad, Ali; Marx, David B.; Wang, Dong; Reinhardt, Richard A.

2011-01-01

Objective This study investigated the role of the prostaglandin (PG) pathway in locally-applied, simvastatin-induced oral bone growth. The possibility of enhancing long-term bone augmentation with an alendronate-based carrier was initiated. Methods Mandibles of 44 mature female rats were treated bilaterally with the following combinations: 2 mg simvastatin in ethanol (SIM-EtOH), EtOH, 2 mg simvastatin acid complexed with alendronate-beta-cyclodextrin conjugate (SIM/ALN-CD), ALN-CD, or ALN. Bone wash technology (injection of PBS and recollection by suction) was used to sample injection sites at baseline (day 0), and 3, 7, 14 and 21 days post-treatment. After 21-24 or 48 days, histomorphometric analysis was done. The amount of PGE2 in bone wash fluid was measured by ELISA, normalized by total protein, and compared between high and low bone growth groups (ANOVA) and correlated with subsequent bone histology at 21 days (Spearman). SIM-stimulated PGE2 synthase and EP4 receptor mRNA in murine osteoblast and fibroblast cell lines were evaluated with real-time PCR. Results Single injections of 2 mg SIM-EtOH induced significantly more new bone than control side after 21 days. PGE2/protein ratios peaked at day 7 and were correlated with the subsequent 21-day new bone width. The correlations at day 14 between PGE2 and new bone width changed to a negative relationship in the test group. SIM-stimulated osteoblasts expressed increased mRNA levels of PGE receptor EP4, while SIM activated PGE synthesis in fibroblasts. SIM/ALN-CD tended to preserve bone long-term. Conclusion Findings suggest that PGE pathway activation and higher levels of PGE2 during the first week following SIM-induced bone growth are desirable, and alendronate-beta-cyclodextrin conjugates not only act as tissue-specific carriers, but preserve new bone. PMID:21438610

A myostatin and activin decoy receptor enhances bone formation in mice.

PubMed

Bialek, P; Parkington, J; Li, X; Gavin, D; Wallace, C; Zhang, J; Root, A; Yan, G; Warner, L; Seeherman, H J; Yaworsky, P J

2014-03-01

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-β (BMP/TGFβ) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The MagAO Giant Accreting Protoplanet Survey (GAPlanetS): Recent Results

NASA Astrophysics Data System (ADS)

Follette, Katherine; Close, Laird; Males, Jared; Morzinski, Katie; Leonard, Clare; MagAO

2018-01-01

I will summarize recent results of the MagAO Giant Accreting Protoplant Survey (GAPlanetS), a search for accreting protoplanets at H-alpha inside of transitional disk gaps. These young, centrally-cleared circumstellar disks are often hosted by stars that are still actively accreting, making it likely that any planets that lie in their central cavities will also be actively accreting. Through differential imaging at Hydrogen-alpha using Magellan's visible light adaptive optics system, we have completed the first systematic search for H-alpha emission from accreting protoplanets in fifteen bright Southern hemisphere transitional disks. I will present results from this survey, including a second epoch on the LkCa 15 system that shows several accreting protoplanet candidates.

Magnetic fields in giant planet formation and protoplanetary discs

NASA Astrophysics Data System (ADS)

Keith, Sarah Louise

2015-12-01

Protoplanetary discs channel accretion onto their host star. How this is achieved is critical to the growth of giant planets which capture their massive gaseous atmosphere from the surrounding flow. Theoretical studies find that an embedded magnetic field could power accretion by hydromagnetic turbulence or torques from a large-scale field. This thesis presents a study of the inuence of magnetic fields in three key aspects of this process: circumplanetary disc accretion, gas flow across gaps in protoplanetary discs, and magnetic-braking in accretion discs. The first study examines the conditions needed for self-consistent accretion driven by magnetic fields or gravitational instability. Models of these discs typically rely on hydromagnetic turbulence as the source of effective viscosity. However, magnetically coupled,accreting regions may be so limited that the disc may not support sufficient inflow. An improved Shakura-Sunyaev ? disc is used to calculate the ionisation fraction and strength of non-ideal effects. Steady magnetically-driven accretion is limited to the thermally ionised, inner disc so that accretion in the remainder of the disc is time-dependent. The second study addresses magnetic flux transport in an accretion gap evacuated by a giant planet. Assuming the field is passively drawn along with the gas, the hydrodynamical simulation of Tanigawa, Ohtsuki & Machida (2012) is used for an a posteriori analysis of the gap field structure. This is used to post-calculate magnetohydrodynamical quantities. This assumption is self-consistent as magnetic forces are found to be weak, and good magnetic coupling ensures the field is frozen into the gas. Hall drift dominates across much of the gap, with the potential to facilitate turbulence and modify the toroidal field according to the global field orientation. The third study considers the structure and stability of magnetically-braked accretion discs. Strong evidence for MRI dead-zones has renewed interest in accretion powered by large-scale fields. An equilibrium model is presented for the radial structure of an axisymmetric, magnetically-braked accretion disc connected to a force-free external field. The accretion rate is multivalued at protoplanetary disc column densities, featuring an `S-curve' associated with models of accretion outbursting. A local, linear analysis of the stability of radial modes finds that the rapidly accreting, middle and upper solution branches are unstable, further highlighting the potential for eruptive accretion events.

The Role of the Outer Boundary Condition in Accretion Disk Models: Theory and Application

NASA Astrophysics Data System (ADS)

Yuan, Feng; Peng, Qiuhe; Lu, Ju-fu; Wang, Jianmin

2000-07-01

In a previous paper, we find that the outer boundary conditions (OBCs) of an optically thin accretion flow play an important role in determining the structure of the flow. Here in this paper, we further investigate the influence of OBCs on the dynamics and radiation of the accretion flow on a more detailed level. Bremsstrahlung and synchrotron radiations amplified by Comptonization are taken into account, and two-temperature plasma assumption is adopted. The three OBCs we adopted are the temperatures of the electrons and ions and the specific angular momentum of the accretion flow at a certain outer boundary. We investigate the individual role of each of the three OBCs on the dynamical structure and the emergent spectrum. We find that when the general parameters such as the mass accretion rate M and the viscous parameter α are fixed the peak flux at various bands such as radio, IR, and X-ray can differ by as much as several orders of magnitude under different OBCs in our example. Our results indicate that the OBC is both dynamically and radiatively important and therefore should be regarded as a new ``parameter'' in accretion disk models. As an illustrative example, we further apply the above results to the compact radio source Sgr A* located at the center of our Galaxy. The advection-dominated accretion flow (ADAF) model has turned out to be a great success in explaining its luminosity and spectrum. However, there exists a discrepancy between the mass accretion rate favored by ADAF models in the literature and that favored by the three-dimensional hydrodynamical simulation, with the former being 10-20 times smaller than the latter. By seriously considering the outer boundary condition of the accretion flow, we find that because of the low specific angular momentum of the accretion gas the accretion in Sgr A* should belong to a new accretion pattern, which is characterized by the possession of a very large sonic radius. This accretion pattern can significantly reduce the discrepancy between the mass accretion rates. We argue that the accretion occurred in some detached binary systems; the core of nearby elliptical galaxies and active galactic nuclei very possibly belongs to this accretion pattern.

Wind accretion and formation of disk structures in symbiotic binary systems

NASA Astrophysics Data System (ADS)

de Val-Borro, M.; Karovska, M.; Sasselov, D. D.; Stone, J. M.

2015-05-01

We investigate gravitationally focused wind accretion in binary systems consisting of an evolved star with a gaseous envelope and a compact accreting companion. We study the mass accretion and formation of an accretion disk around the secondary caused by the strong wind from the primary late-type component using global 2D and 3D hydrodynamic numerical simulations. In particular, the dependence of the mass accretion rate on the mass loss rate, wind temperature and orbital parameters of the system is considered. For a typical slow and massive wind from an evolved star the mass transfer through a focused wind results in rapid infall onto the secondary. A stream flow is created between the stars with accretion rates of a 2--10% percent of the mass loss from the primary. This mechanism could be an important method for explaining periodic modulations in the accretion rates for a broad range of interacting binary systems and fueling of a large population of X-ray binary systems. We test the plausibility of these accretion flows indicated by the simulations by comparing with observations of the symbiotic variable system CH Cyg.

Foundations of Black Hole Accretion Disk Theory.

PubMed

Abramowicz, Marek A; Fragile, P Chris

2013-01-01

This review covers the main aspects of black hole accretion disk theory. We begin with the view that one of the main goals of the theory is to better understand the nature of black holes themselves. In this light we discuss how accretion disks might reveal some of the unique signatures of strong gravity: the event horizon, the innermost stable circular orbit, and the ergosphere. We then review, from a first-principles perspective, the physical processes at play in accretion disks. This leads us to the four primary accretion disk models that we review: Polish doughnuts (thick disks), Shakura-Sunyaev (thin) disks, slim disks, and advection-dominated accretion flows (ADAFs). After presenting the models we discuss issues of stability, oscillations, and jets. Following our review of the analytic work, we take a parallel approach in reviewing numerical studies of black hole accretion disks. We finish with a few select applications that highlight particular astrophysical applications: measurements of black hole mass and spin, black hole vs. neutron star accretion disks, black hole accretion disk spectral states, and quasi-periodic oscillations (QPOs).

Effect of nuclear stars gravity on quasar radiation feedback on the parsec-scale

NASA Astrophysics Data System (ADS)

Yang, Xiao-Hong; Bu, De-Fu

2018-05-01

It is often suggested that a super massive black hole is embedded in a nuclear bulge of size of a few 102 parsec . The nuclear stars gravity is not negligible near ˜10parsec. In order to study the effect of nuclear stars gravity on quasar radiation feedback on the parsec scale, we have simulated the parsec scale flows irradiated by a quasar by taking into account the gravitational potential of both the black hole and the nuclear star cluster. We find that the effect of nuclear stars gravity on the parsec-scale flows is related to the fraction of X-ray photons in quasar radiation. For the models in which the fraction of X-ray photons is not small (e.g. the X-ray photons contribute to 20% of the quasar radiation), the nuclear stars gravity is very helpful to collimate the outflows driven by UV photons, significantly weakens the outflow power at the outer boundary and significantly enhances the net accretion rate onto the black hole. For the models in which X-ray photons are significantly decreased (e.g. the X-ray photons contribute to 5% of the quasar radiation), the nuclear stars gravity can just slightly change properties of outflow and slightly enhance the net accretion rate onto the black hole.

Effects of Thermonuclear X-Ray Bursts on Non-burst Emissions in the Soft State of 4U 1728–34

NASA Astrophysics Data System (ADS)

Bhattacharyya, Sudip; Yadav, J. S.; Sridhar, Navin; Verdhan Chauhan, Jai; Agrawal, P. C.; Antia, H. M.; Pahari, Mayukh; Misra, Ranjeev; Katoch, Tilak; Manchanda, R. K.; Paul, Biswajit

2018-06-01

It has recently been shown that the persistent emission of a neutron star low-mass X-ray binary (LMXB) evolves during a thermonuclear (type-I) X-ray burst. The reason of this evolution, however, is not fully known. This uncertainty can introduce significant systematics in the neutron star radius measurement using burst spectra, particularly if an unknown but significant fraction of the burst emission, which is reprocessed, contributes to the changes in the persistent emission during the burst. Here, by analyzing individual burst data of AstroSat/LAXPC from the neutron star LMXB 4U 1728–34 in the soft state, we show that the burst emission is not significantly reprocessed by a corona covering the neutron star. Rather, our analysis suggests that the burst emission enhances the accretion disk emission, possibly by increasing the accretion rate via disk. This enhanced disk emission, which is Comptonized by a corona covering the disk, can explain an increased persistent emission observed during the burst. This finding provides an understanding of persistent emission components and their interaction with the thermonuclear burst emission. Furthermore, as burst photons are not significantly reprocessed, non-burst and burst emissions can be reliably separated, which is required to reduce systematic uncertainties in the stellar radius measurement.

Kelvin-Helmholtz instabilities as the source of inhomogeneous mixing in nova explosions.

PubMed

Casanova, Jordi; José, Jordi; García-Berro, Enrique; Shore, Steven N; Calder, Alan C

2011-10-19

Classical novae are thermonuclear explosions in binary stellar systems containing a white dwarf accreting material from a close companion star. They repeatedly eject 10(-4)-10(-5) solar masses of nucleosynthetically enriched gas into the interstellar medium, recurring on intervals of decades to tens of millennia. They are probably the main sources of Galactic (15)N, (17)O and (13)C. The origin of the large enhancements and inhomogeneous distribution of these species observed in high-resolution spectra of ejected nova shells has, however, remained unexplained for almost half a century. Several mechanisms, including mixing by diffusion, shear or resonant gravity waves, have been proposed in the framework of one-dimensional or two-dimensional simulations, but none has hitherto proven successful because convective mixing can only be modelled accurately in three dimensions. Here we report the results of a three-dimensional nuclear-hydrodynamic simulation of mixing at the core-envelope interface during nova outbursts. We show that buoyant fingering drives vortices from the Kelvin-Helmholtz instability, which inevitably enriches the accreted envelope with material from the outer white-dwarf core. Such mixing also naturally produces large-scale chemical inhomogeneities. Both the metallicity enhancement and the intrinsic dispersions in the abundances are consistent with the observed values.

Persistent IGF-I overexpression in skeletal muscle transiently enhances DNA accretion and growth.

PubMed

Fiorotto, Marta L; Schwartz, Robert J; Delaughter, M Craig

2003-01-01

Adult transgenic mice with muscle-specific overexpression of insulin-like growth factor (IGF)-I have enlarged skeletal muscles. In this study, we; 1) characterized the development of muscle hypertrophy with respect to fiber type, age, and sex; 2) determined the primary anabolic process responsible for development of hypertrophy; and 3) identified secondary effects of muscle hypertrophy on body composition. Transgene expression increased with age and was present only in fibers expressing type IIB fast myosin heavy chain. Muscle masses were greater by 5 wk of age, and by 10 wk of age the differences were maximal despite continued transgene expression. Total DNA and RNA contents of the gastrocnemius muscle were greater for transgenic mice than for nontransgenic littermates. The differences were maximal by 5 wk of age and preceded the increase in protein mass. The accelerated protein deposition ceased when the protein/DNA ratio attained the same value as in nontransgenic controls. Despite localization of IGF-I expression to muscle without changes in plasma IGF-I concentrations, genotype also modified the normal age and sex effects on fat deposition and organ growth. Thus, enhanced DNA accretion by IGF-I was primarily responsible for stimulating muscle growth. In turn, secondary effects on body composition were incurred that likely reflect the impact of muscle mass on whole body metabolism.

Synthetic octacalcium phosphate: a possible carrier for mesenchymal stem cells in bone regeneration.

PubMed

Suzuki, Osamu; Anada, Takahisa

2013-01-01

The present paper reviews biomaterial studies of synthetic octacalcium phosphate (OCP) as a scaffold of osteoblastic cells. OCP crystals have been suggested to be one of precursor phases in hydroxyapatite (HA) crystal formation in bone and tooth. The recent intensive biomaterials and tissue engineering studies using synthetic OCP disclosed the potential function of OCP as a bioactive material as well as synthetic HA materials due to its highly osteoconductive and biodegradable properties. In vitro studies showed that OCP crystals exhibit a positive effect on osteoblastic cell differentiation. In vivo studies confirmed that the materials of OCP in a granule forms and OCP-based composite materials with natural polymers, such as gelatin and collagen, enhance bone regeneration if implanted in various model bone defects with critical-sized diameters, defined as a defect which does not heal spontaneously throughout the lifetime of the animals. One of particular characteristics of OCP, found as a mechanism to enhance bone regeneration in vivo, is a process of progressive conversion from OCP to HA at physiological conditions. The OCP-HA conversion is accompanied by progressive physicochemical changes of the material properties, which affects the tissue reaction around the crystals where osteoblastic cells are encountered. Mesenchymal stem cells (MSCs) seeded in an OCP-based material enhanced bone regeneration in the rat critical-sized calvaria defect more than that by the material alone. The overall results reveal that OCP crystals have an effect on osteoblastic cell differentiation including the differentiation of MSCs in vivo. The evidence collected experimentally in the laboratory was presented.

Enhanced Osteogenesis by Reduced Graphene Oxide/Hydroxyapatite Nanocomposites

PubMed Central

Lee, Jong Ho; Shin, Yong Cheol; Lee, Sang-Min; Jin, Oh Seong; Kang, Seok Hee; Hong, Suck Won; Jeong, Chang-Mo; Huh, Jung Bo; Han, Dong-Wook

2015-01-01

Recently, graphene-based nanomaterials, in the form of two dimensional substrates or three dimensional foams, have attracted considerable attention as bioactive scaffolds to promote the differentiation of various stem cells towards specific lineages. On the other hand, the potential advantages of using graphene-based hybrid composites directly as factors inducing cellular differentiation as well as tissue regeneration are unclear. This study examined whether nanocomposites of reduced graphene oxide (rGO) and hydroxyapatite (HAp) (rGO/HAp NCs) could enhance the osteogenesis of MC3T3-E1 preosteoblasts and promote new bone formation. When combined with HAp, rGO synergistically promoted the spontaneous osteodifferentiation of MC3T3-E1 cells without hindering their proliferation. This enhanced osteogenesis was corroborated from determination of alkaline phosphatase activity as early stage markers of osteodifferentiation and mineralization of calcium and phosphate as late stage markers. Immunoblot analysis showed that rGO/HAp NCs increase the expression levels of osteopontin and osteocalcin significantly. Furthermore, rGO/HAp grafts were found to significantly enhance new bone formation in full-thickness calvarial defects without inflammatory responses. These results suggest that rGO/HAp NCs can be exploited to craft a range of strategies for the development of novel dental and orthopedic bone grafts to accelerate bone regeneration because these graphene-based composite materials have potentials to stimulate osteogenesis. PMID:26685901

Induction of quiescence (G0) in bone marrow stromal stem cells enhances their stem cell characteristics.

PubMed

Rumman, Mohammad; Majumder, Abhijit; Harkness, Linda; Venugopal, Balu; Vinay, M B; Pillai, Malini S; Kassem, Moustapha; Dhawan, Jyotsna

2018-05-17

Several studies have suggested that bone marrow stromal steam cells (BMSC) exist in a quiescent state (G0) within the in vivo niche; however, an explicit analysis of the biology of G0 state-BMSC has not been reported. We hypothesized that induction of G0 in BMSC might enhance their stem cell properties. Thus, we induced quiescence in BMSC in vitro by (a) suspension culture in a viscous medium or (b) culture on soft polyacrylamide substrate; and examined their molecular and functional phenotype. Induction of G0 was confirmed by bromo-deoxyuridine (BrdU) labelling and analysis of cell cycle gene expression. Upon reactivation and re-entry into cell cycle, G0 state-BMSC exhibited enhanced clonogenic self-renewal, preferential differentiation into osteoblastic rather than adipocytic cells and increased ectopic bone formation when implanted subcutaneously in vivo in immune-deficient mice, compared to asynchronous proliferating (pre-G0) BMSC. Global gene expression profiling revealed reprogramming of the transcriptome during G0 state including significant alterations in relevant pathways and expression of secreted factors, suggesting altered autocrine and paracrine signaling by G0 state-BMSC and a possible mechanism for enhanced bone formation. G0 state-BMSC might provide a clinically relevant model for understanding the in vivo biology of BMSC. Copyright © 2018. Published by Elsevier B.V.

Vibration paradox in orthodontics: Anabolic and catabolic effects

PubMed Central

Alikhani, Mani; Alansari, Sarah; Hamidaddin, Mohammad A.; Sangsuwon, Chinapa; Alyami, Bandar; Thirumoorthy, Soumya N.; Oliveira, Serafim M.; Nervina, Jeanne M.

2018-01-01

Vibration in the form of High Frequency Acceleration (HFA) is anabolic on the craniofacial skeleton in the absence of inflammation. Orthodontic forces trigger an inflammation-dependent catabolic cascade that is crucial for tooth movement. It is unknown what effect HFA has on alveolar bone if applied during orthodontic treatment. The objectives of this study are to examine the effect of HFA on the rate of tooth movement and alveolar bone, and determine the mechanism by which HFA affects tooth movement. Adult Sprague Dawley rats were divided to control, orthodontic force alone (OTM), and different experimental groups that received the same orthodontic forces and different HFA regimens. Orthodontic tooth movement was assessed when HFA parameters, frequency, acceleration, duration of exposure, and direct or indirect application were varied. We found that HFA treatment significantly enhanced the inflammation-dependent catabolic cascade during orthodontic tooth movement. HFA treatment increased inflammatory mediators and osteoclastogenesis, and decreased alveolar bone density during orthodontic tooth movement. Each of the HFA variables produced significant changes in the rate of tooth movement and the effect was PDL-dependent. This is the first report that HFA enhances inflammation-dependent catabolic cascades in bone. The clinical implications of our study are highly significant, as HFA can be utilized to enhance the rate of orthodontic tooth movement during the catabolic phase of treatment and subsequently be utilized to enhance retention during the anabolic remodeling phase after orthodontic forces are removed. PMID:29734391

Enhanced MC3T3-E1 preosteoblast response and bone formation on the addition of nano-needle and nano-porous features to microtopographical titanium surfaces.

PubMed

Zhuang, X-M; Zhou, B; Ouyang, J-L; Sun, H-P; Wu, Y-L; Liu, Q; Deng, F-L

2014-08-01

Micro/nanotopographical modifications on titanium surfaces constitute a new process to increase osteoblast response to enhance bone formation. In this study, we utilized alkali heat treatment at high (SB-AH1) and low temperatures (SB-AH2) to nano-modify sandblasted titanium with microtopographical surfaces. Then, we evaluated the surface properties, biocompatibility and osteogenic capability of SB-AH1 and SB-AH2 in vitro and in vivo, and compared these with conventional sandblast-acid etching (SLA) and Ti control surfaces. SB-AH1 and SB-AH2 surfaces exhibited micro/nanotopographical modifications of nano-needle structures and nano-porous network layers, respectively, compared with the sole microtopographical surface of macro and micro pits on the SLA surface and the relatively smooth surface on the Ti control. SB-AH1 and SB-AH2 showed different roughness and elemental components, but similar wettability. MC3T3-E1 preosteoblasts anchored closely on the nanostructures of SB-AH1 and SB-AH2 surfaces, and these two surfaces more significantly enhanced cell proliferation and alkaline phosphatase (ALP) activity than others, while the SB-AH2 surface exhibited better cell proliferation and higher ALP activity than SB-AH1. All four groups of titanium domes with self-tapping screws were implanted in rabbit calvarial bone models, and these indicated that SB-AH1 and SB-AH2 surfaces achieved better peri-implant bone formation and implant stability, while the SB-AH2 surface achieved the best percentage of bone-implant contact (BIC%). Our study demonstrated that the micro/nanotopographical surface generated by sandblasting and alkali heat treatment significantly enhanced preosteoblast proliferation, ALP activity and bone formation in vitro and in vivo, and nano-porous network topography may further induce better preosteoblast proliferation, ALP activity and BIC%.

Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases.

PubMed

Ke, Hua Zhu; Richards, William G; Li, Xiaodong; Ominsky, Michael S

2012-10-01

The processes of bone growth, modeling, and remodeling determine the structure, mass, and biomechanical properties of the skeleton. Dysregulated bone resorption or bone formation may lead to metabolic bone diseases. The Wnt pathway plays an important role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of sclerostin leads to substantially increased bone mass in humans and in genetically manipulated animals. Studies in various animal models of bone disease have shown that inhibition of sclerostin using a monoclonal antibody (Scl-Ab) increases bone formation, density, and strength. Additional studies show that Scl-Ab improves bone healing in models of bone repair. Inhibition of DKK1 by monoclonal antibody (DKK1-Ab) stimulates bone formation in younger animals and to a lesser extent in adult animals and enhances fracture healing. Thus, sclerostin and DKK1 are emerging as the leading new targets for anabolic therapies to treat bone diseases such as osteoporosis and for bone repair. Clinical trials are ongoing to evaluate the effects of Scl-Ab and DKK1-Ab in humans for the treatment of bone loss and for bone repair.

Constraints on two accretion disks centered on the equatorial plane of a Kerr SMBH

NASA Astrophysics Data System (ADS)

Pugliese, Daniela; Stuchlík, Zdeněk

2017-12-01

The possibility that two toroidal accretion configurations may be orbiting around a super–massive Kerr black hole has been addressed. Such tori may be formed during different stages of the Kerr attractor accretion history. We consider the relative rotation of the tori and the corotation or counterrotation of a single torus with respect to the Kerr attractor. We give classification of the couples of accreting and non–accreting tori in dependence on the Kerr black hole dimensionless spin. We demonstrate that only in few cases a double accretion tori system may be formed under specific conditions.

A Particular Appetite: Cosmological Hydrodynamic Simulations of Preferential Accretion in the Supermassive Black Holes of Milky Way Size Galaxies

NASA Astrophysics Data System (ADS)

Sanchez, Natalie; Bellovary, Jillian M.; Holley-Bockelmann, Kelly

2016-01-01

With the use of cosmological hydrodynamic simulations of Milky Way-type galaxies, we identify the preferential source of gas that is accreted by the supermassive black holes (SMBHs) they host. We examine simulations of two Milky Way analogs, each distinguished by a differing merger history. One galaxy is characterized by several major mergers and the other has a more quiescent history. By examining and comparing these two galaxies, which have a similar structure at z=0, we asses the importance of merger history on black hole accretion. This study is an extension of Bellovary et. al. 2013, which studied accretion onto SMBHs in massive, high redshift galaxies. Bellovary found that the fraction of gas accreted by the galaxy was proportional to that which was accreted by its SMBH. Contrary to Bellovary's previous results, we found that though the gas accreted by a quiescent galaxy will mirror the accretion of its central SMBH, a galaxy that is characterized by an active merger history will have a SMBH that preferentially accretes gas gained through mergers. We move forward by examining the angular momentum of the gas accreted by these Milky Way-type galaxies to better understand the mechanisms fueling their central SMBH.

Stunted accretion growth of black holes by combined effect of the flow angular momentum and radiation feedback

NASA Astrophysics Data System (ADS)

Sugimura, Kazuyuki; Hosokawa, Takashi; Yajima, Hidenobu; Inayoshi, Kohei; Omukai, Kazuyuki

2018-05-01

Accretion on to seed black holes (BHs) is believed to play a crucial role in formation of supermassive BHs observed at high-redshift (z > 6). Here, we investigate the combined effect of gas angular momentum and radiation feedback on the accretion flow, by performing 2D axially symmetric radiation hydrodynamics simulations that solve the flow structure across the Bondi radius and the outer part of the accretion disc simultaneously. The accreting gas with finite angular momentum forms a rotationally-supported disc inside the Bondi radius, where the accretion proceeds by the angular momentum transport due to assumed α-type viscosity. We find that the interplay of radiation and angular momentum significantly suppresses accretion even if the radiative feedback is weakened in an equatorial shadowing region. The accretion rate is O(α) ˜ O(0.01 - 0.1) times the Bondi value, where α is the viscosity parameter. By developing an analytical model, we show that such a great reduction of the accretion rate persists unless the angular momentum is so small that the corresponding centrifugal radius is ≲ 0.04 times the Bondi radius. We argue that BHs are hard to grow quickly via rapid mass accretion considering the angular momentum barrier presented in this paper.

Genomic deletion of a long-range bone enhancer misregulatessclerostin in Van Buchem disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loots, Gabriela G.; Kneissel, Michaela; Keller, Hansjoerg

2005-04-15

Mutations in distant regulatory elements can negatively impact human development and health, yet due to the difficulty of detecting these critical sequences we predominantly focus on coding sequences for diagnostic purposes. We have undertaken a comparative sequence-based approach to characterize a large noncoding region deleted in patients affected by Van Buchem disease (VB), a severe sclerosing bone dysplasia. Using BAC recombination and transgenesis we characterized the expression of human sclerostin (sost) from normal (hSOSTwt) or Van Buchem(hSOSTvb D) alleles. Only the hSOSTwt allele faithfully expressed high levels of human sost in the adult bone and impacted bone metabolism, consistent withmore » the model that the VB noncoding deletion removes a sost specific regulatory element. By exploiting cross-species sequence comparisons with in vitro and in vivo enhancer assays we were able to identify a candidate enhancer element that drives human sost expression in osteoblast-like cell lines in vitro and in the skeletal anlage of the E14.5 mouse embryo, and discovered a novel function for sclerostin during limb development. Our approach represents a framework for characterizing distant regulatory elements associated with abnormal human phenotypes.« less

Novel strontium-doped bioactive glass nanoparticles enhance proliferation and osteogenic differentiation of human bone marrow stromal cells

NASA Astrophysics Data System (ADS)

Strobel, L. A.; Hild, N.; Mohn, D.; Stark, W. J.; Hoppe, A.; Gbureck, U.; Horch, R. E.; Kneser, U.; Boccaccini, A. R.

2013-07-01

The present study investigates a new family of bioactive glass nanoparticles with and without Sr-doping focusing on the influence of the nanoparticles on human bone marrow stromal cells (hBMSCs) in vitro. The bioactive glass nanoparticles were fabricated by flame spray synthesis and a particle diameter of 30-35 nm was achieved. Glass nanoparticles were undoped (BG 13-93-0Sr) or doped with 5 wt% strontium (Sr) (BG 13-93-5Sr) and used at concentrations of 10 and 100 μg/cm² (particles per culture plate area), respectively. Cells were cultured for 14 days after which the samples were analysed regarding metabolic activity and expression of various bone-specific genes. Cell growth and morphology indicated the high cytocompatibility of the nanoparticulate bioactive glass. The presence of the nanoparticles enhanced cell growth compared to the plain polystyrene control group. At a concentration of 100 μg/cm², Sr-doped particles led to significantly enhanced gene expression of osteocalcin, collagen type 1 and vascular endothelial growth factor. Thus, Sr-doped nanoparticles showing a dose-dependent increase of osteogenic differentiation in hBMSCs are a promising biomaterial for bone regeneration purposes.

Fundamental Ice Crystal Accretion Physics Studies

NASA Technical Reports Server (NTRS)

Struk, Peter M.; Broeren, Andy P.; Tsao, Jen-Ching; Vargas, Mario; Wright, William B.; Currie, Tom; Knezevici, Danny; Fuleki, Dan

2012-01-01

Due to numerous engine power-loss events associated with high-altitude convective weather, ice accretion within an engine due to ice crystal ingestion is being investigated. The National Aeronautics and Space Administration (NASA) and the National Research Council (NRC) of Canada are starting to examine the physical mechanisms of ice accretion on surfaces exposed to ice-crystal and mixed-phase conditions. In November 2010, two weeks of testing occurred at the NRC Research Altitude Facility utilizing a single wedge-type airfoil designed to facilitate fundamental studies while retaining critical features of a compressor stator blade or guide vane. The airfoil was placed in the NRC cascade wind tunnel for both aerodynamic and icing tests. Aerodynamic testing showed excellent agreement compared with CFD data on the icing pressure surface and allowed calculation of heat transfer coefficients at various airfoil locations. Icing tests were performed at Mach numbers of 0.2 to 0.3, total pressures from 93 to 45 kPa, and total temperatures from 5 to 15 C. Ice and liquid water contents ranged up to 20 and 3 g/m3, respectively. The ice appeared well adhered to the surface in the lowest pressure tests (45 kPa) and, in a particular case, showed continuous leading-edge ice growth to a thickness greater than 15 mm in 3 min. Such widespread deposits were not observed in the highest pressure tests, where the accretions were limited to a small area around the leading edge. The suction surface was typically ice-free in the tests at high pressure, but not at low pressure. The icing behavior at high and low pressure appeared to be correlated with the wet-bulb temperature, which was estimated to be above 0 C in tests at 93 kPa and below 0 C in tests at lower pressure, the latter enhanced by more evaporative cooling of water. The authors believe that the large ice accretions observed in the low pressure tests would undoubtedly cause the aerodynamic performance of a compressor component such as a stator blade to degrade significantly, and could damage downstream components if shed.

Fundamental Ice Crystal Accretion Physics Studies

NASA Technical Reports Server (NTRS)

Currie, Tom; Knezevici, Danny; Fuleki, Dan; Struk, Peter M.; Broeren, Andy P.; Tsao, Jen-ching; Vargas, Mario; Wright, William

2011-01-01

Due to numerous engine power-loss events associated with high-altitude convective weather, ice accretion within an engine due to ice-crystal ingestion is being investigated. The National Aeronautics and Space Administration (NASA) and the National Research Council (NRC) of Canada are starting to examine the physical mechanisms of ice accretion on surfaces exposed to ice-crystal and mixed-phase conditions. In November 2010, two weeks of testing occurred at the NRC Research Altitude Facility utilizing a single wedge-type airfoil designed to facilitate fundamental studies while retaining critical features of a compressor stator blade or guide vane. The airfoil was placed in the NRC cascade wind tunnel for both aerodynamic and icing tests. Aerodynamic testing showed excellent agreement compared with CFD data on the icing pressure surface and allowed calculation of heat transfer coefficients at various airfoil locations. Icing tests were performed at Mach numbers of 0.2 to 0.3, total pressures from 93 to 45 kPa, and total temperatures from 5 to 15 C. Ice and liquid water contents ranged up to 20 and 3 grams per cubic meter, respectively. The ice appeared well adhered to the surface in the lowest pressure tests (45 kPa) and, in a particular case, showed continuous leading-edge ice growth to a thickness greater than 15 millimeters in 3 minutes. Such widespread deposits were not observed in the highest pressure tests, where the accretions were limited to a small area around the leading edge. The suction surface was typically ice-free in the tests at high pressure, but not at low pressure. The icing behavior at high and low pressure appeared to be correlated with the wet-bulb temperature, which was estimated to be above 0 C in tests at 93 kPa and below 0 C in tests at lower pressure, the latter enhanced by more evaporative cooling of water. The authors believe that the large ice accretions observed in the low pressure tests would undoubtedly cause the aerodynamic performance of a compressor component such as a stator blade to degrade significantly, and could damage downstream components if shed.

Guided bone augmentation using ceramic space-maintaining devices: the impact of chemistry

PubMed Central

Anderud, Jonas; Abrahamsson, Peter; Jimbo, Ryo; Isaksson, Sten; Adolfsson, Erik; Malmström, Johan; Naito, Yoshihito; Wennerberg, Ann

2015-01-01

The purpose of the study was to evaluate histologically, whether vertical bone augmentation can be achieved using a hollow ceramic space maintaining device in a rabbit calvaria model. Furthermore, the chemistry of microporous hydroxyapatite and zirconia were tested to determine which of these two ceramics are most suitable for guided bone generation. 24 hollow domes in two different ceramic materials were placed subperiosteal on rabbit skull bone. The rabbits were sacrificed after 12 weeks and the histology results were analyzed regarding bone-to-material contact and volume of newly formed bone. The results suggest that the effect of the microporous structure of hydroxyapatite seems to facilitate for the bone cells to adhere to the material and that zirconia enhance a slightly larger volume of newly formed bone. In conclusion, the results of the current study demonstrated that ceramic space maintaining devices permits new bone formation and osteoconduction within the dome. PMID:25792855

The effects and mechanisms of clinorotation on proliferation and differentiation in bone marrow mesenchymal stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Ming; Wang, Yongchun; Yang, Min

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cellmore » cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs. - Highlights: • Simulated microgravity inhibited proliferation and differentiation in BMSCs. • The decreased proliferation due to blocked cell cycle and enhanced the apoptosis. • The inhibited differentiation accounts for alteration of SATB2, Hoxa2 and Cbfa1.« less

Si-doping bone composite based on protein template-mediated assembly for enhancing bone regeneration

NASA Astrophysics Data System (ADS)

Yang, Qin; Du, Yingying; Wang, Yifan; Wang, Zhiying; Ma, Jun; Wang, Jianglin; Zhang, Shengmin

2017-06-01

Bio-inspired hybrid materials that contain organic and inorganic networks interpenetration at the molecular level have been a particular focus of interest on designing novel nanoscale composites. Here we firstly synthesized a series of hybrid bone composites, silicon-hydroxyapatites/silk fibroin/collagen, based on a specific molecular assembled strategy. Results of material characterization confirmed that silicate had been successfully doped into nano-hydroxyapatite lattice. In vitro evaluation at the cellular level clearly showed that these Si-doped composites were capable of promoting the adhesion and proliferation of rat mesenchymal stem cells (rMSCs), extremely enhancing osteoblastic differentiation of rMSCs compared with silicon-free composite. More interestingly, we found there was a critical point of silicon content in the composition on regulating multiple cell behaviors. In vivo animal evaluation further demonstrated that Si-doped composites enabled to significantly improve the repair of cranial bone defect. Consequently, our current work not only suggests fabricating a potential bone repair materials by integrating element-doping and molecular assembled strategy in one system, but also paves a new way for constructing multi-functional composite materials in the future.

Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

DTIC Science & Technology

2014-10-03

frac tures? J Orthop Res 29, 33, 2011. Epub 2010/07/08. 2. Russell, T.A., and Leighton , R.K. Comparison of autogenous bone graft and endothermic...Boyd, S.K., Christiansen , B.A., Guldberg, R.E., Jepsen, K.J., and Muller, R. Guidelines for assessment of bone microstructure in rodents using micro

PTH promotes allograft integration in a calvarial bone defect.

PubMed

Sheyn, Dmitriy; Cohn Yakubovich, Doron; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M; Gazit, Dan; Gazit, Zulma

2013-12-02

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and microcomputed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in allograft + PTH treated mice comparing to allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment.

TRAF family member-associated NF-κB activator (TANK) is a negative regulator of osteoclastogenesis and bone formation.

PubMed

Maruyama, Kenta; Kawagoe, Tatsukata; Kondo, Takeshi; Akira, Shizuo; Takeuchi, Osamu

2012-08-17

The differentiation of bone-resorbing osteoclasts is induced by RANKL signaling, and leads to the activation of NF-κB via TRAF6 activation. TRAF family member-associated NF-κB activator (TANK) acts as a negative regulator of Toll-like receptors (TLRs) and B-cell receptor (BCR) signaling by inhibiting TRAF6 activation. Tank(-/-) mice spontaneously develop autoimmune glomerular nephritis in an IL-6-dependent manner. Despite its importance in the TCRs and BCR-activated TRAF6 inhibition, the involvement of TANK in RANKL signaling is poorly understood. Here, we report that TANK is a negative regulator of osteoclast differentiation. The expression levels of TANK mRNA and protein were up-regulated during RANKL-induced osteoclastogenesis, and overexpression of TANK in vitro led to a decrease in osteoclast formation. The in vitro osteoclastogenesis of Tank(-/-) cells was significantly increased, accompanied by increased ubiquitination of TRAF6 and enhanced canonical NF-κB activation in response to RANKL stimulation. Tank(-/-) mice showed severe trabecular bone loss, but increased cortical bone mineral density, because of enhanced bone erosion and formation. TANK mRNA expression was induced during osteoblast differentiation and Tank(-/-) osteoblasts exhibited enhaced NF-κB activation, IL-11 expression, and bone nodule formation than wild-type control cells. Finally, wild-type mice transplanted with bone marrow cells from Tank(-/-) mice showed trabecular bone loss analogous to that in Tank(-/-) mice. These findings demonstrate that TANK is critical for osteoclastogenesis by regulating NF-κB, and is also important for proper bone remodeling.

TRAF Family Member-associated NF-κB Activator (TANK) Is a Negative Regulator of Osteoclastogenesis and Bone Formation*

PubMed Central

Maruyama, Kenta; Kawagoe, Tatsukata; Kondo, Takeshi; Akira, Shizuo; Takeuchi, Osamu

2012-01-01

The differentiation of bone-resorbing osteoclasts is induced by RANKL signaling, and leads to the activation of NF-κB via TRAF6 activation. TRAF family member-associated NF-κB activator (TANK) acts as a negative regulator of Toll-like receptors (TLRs) and B-cell receptor (BCR) signaling by inhibiting TRAF6 activation. Tank−/− mice spontaneously develop autoimmune glomerular nephritis in an IL-6-dependent manner. Despite its importance in the TCRs and BCR-activated TRAF6 inhibition, the involvement of TANK in RANKL signaling is poorly understood. Here, we report that TANK is a negative regulator of osteoclast differentiation. The expression levels of TANK mRNA and protein were up-regulated during RANKL-induced osteoclastogenesis, and overexpression of TANK in vitro led to a decrease in osteoclast formation. The in vitro osteoclastogenesis of Tank−/− cells was significantly increased, accompanied by increased ubiquitination of TRAF6 and enhanced canonical NF-κB activation in response to RANKL stimulation. Tank−/− mice showed severe trabecular bone loss, but increased cortical bone mineral density, because of enhanced bone erosion and formation. TANK mRNA expression was induced during osteoblast differentiation and Tank−/− osteoblasts exhibited enhaced NF-κB activation, IL-11 expression, and bone nodule formation than wild-type control cells. Finally, wild-type mice transplanted with bone marrow cells from Tank−/− mice showed trabecular bone loss analogous to that in Tank−/− mice. These findings demonstrate that TANK is critical for osteoclastogenesis by regulating NF-κB, and is also important for proper bone remodeling. PMID:22773835

Acute changes in biochemical markers of bone resorption and formation after Thai traditional massage.

PubMed

Saetung, Sunee; Chailurkit, La-or; Ongphiphadhanakul, Boonsong

2010-07-01

Mechanical loadings by active exercise or passive low amplitude vibration have been demonstrated to enhance bone mass or delay bone loss. Traditional Thai massage can be anabolic to bone due to the application of physical loading on the body in a rhythmic fashion. To explore the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover immediately after the massage. Subjects consisted of 30 healthy females aged 20-40 years. Each subject received Thai traditional massage for 2 hours by a single masseuse. Bone mineral density (BMD) at baseline was measured by dual-energy X-ray absorptiometry (DEXA). C-terminal telopeptide of type 1 collagen (CTx-I) and total procollagen type 1 amino-terminal propeptide (P1NP) were determined by electrochemiluminescence immunoassay. There was a 4.8% increase in serum P1NP concentrations after massage (median 43.4 ng/ml vs. 41.3 ng/ml, p < 0.05). Serum CTx-I also decreased after massage (median 2-hour vs. baseline 0.29 ng/ml vs. 0.31 ng/ml, p < 0.05). There was a nearly significant negative correlation between the percentage change in serum P1NP and BMD at the total femur (r = -0.37, p = 0.056) whereas the statistically significant correlation disappeared between percentage change in bone turnover and the other sites of BMD. Thai traditional massage induces acute changes in bone formation and resorption markers. Study on the more prolonged effects of Thai traditional massage is warranted to explore its implication in the enhancement of bone health.

Fas/S1P1 crosstalk via NF-κB activation in osteoclasts controls subchondral bone remodeling in murine TMJ arthritis.

PubMed

Hutami, Islamy Rahma; Izawa, Takashi; Mino-Oka, Akiko; Shinohara, Takehiro; Mori, Hiroki; Iwasa, Akihiko; Tanaka, Eiji

2017-09-02

Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice. Initially, greater osteoclast production was observed in vitro from bone marrow macrophages obtained from MRL/lpr mice due to enhanced phosphorylation of NF-κB, as well as Akt and MAPK, to receptor activator of nuclear factor-κB ligand (RANKL). Expression of sphingosine 1-phosphate receptor 1 (S1P 1 ) was also significantly upregulated in the condylar cartilage. S1P 1 was found to be required for S1P-induced migration of osteoclast precursor cells and downstream signaling via Rac1. When SN50, a synthetic NF-κB-inhibitory peptide, was applied to the MRL/lpr mice, subchondral trabecular bone loss was reduced and both production of osteoclastogenesis markers and sphingosine kinase (Sphk) 1/S1P 1 signaling were reduced. Thus, the present results suggest that Fas/S1P 1 signaling via activation of NF-κB in osteoclast precursor cells is a key factor in the pathogenesis of RA in the TMJ. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone regeneration with active angiogenesis by basic fibroblast growth factor gene transfected mesenchymal stem cells seeded on porous beta-TCP ceramic scaffolds.

PubMed

Guo, Xiaodong; Zheng, Qixin; Kulbatski, Iris; Yuan, Quan; Yang, Shuhua; Shao, Zengwu; Wang, Hong; Xiao, Baojun; Pan, Zhengqi; Tang, Shuo

2006-09-01

Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focused on combining gene transfer with tissue engineering techniques. Basic fibroblast growth factor (bFGF) is one of the most prominent osteogenic growth factors that has the potential to accelerate bone healing by promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) and the regeneration of capillary vasculature. However, the short biological half-lives of growth factors may impose severe restraints on their clinical usefulness. Gene-based delivery systems provide a better way of achieving a sustained high concentration of growth factors locally in the defect and delivering a more biologically active product than that achieved by exogenous application of recombinant proteins. The objective of this experimental study was to investigate whether the bFGF gene modified MSCs could enhance the repair of large segmental bone defects. The pcDNA3-bFGF gene transfected MSCs were seeded on biodegradable porous beta tricalcium phosphate (beta-TCP) ceramics and allografted into the 15 mm critical-sized segmental bone defects in the radius of 18 New Zealand White rabbits. The pcDNA3 vector gene transfected MSCs were taken as the control. The follow-up times were 2, 4, 6, 8, 10 and 12 weeks. Scanning electron microscopic, roentgenographic, histologic and immunohistological studies were used to assess angiogenesis and bone regeneration. In vitro, the proliferation and differentiation of bFGF gene transfected MSCs were more active than that of the control groups. In vivo, significantly more new bone formation accompanied by abundant active capillary regeneration was observed in pores of the ceramics loaded with bFGF gene transfected MSCs, compared with control groups. Transfer of gene encoding bFGF to MSCs increases their osteogenic properties by enhancing capillary regeneration, thus providing a rich blood supply for new bone formation. This new bFGF gene enhanced tissue engineering strategy could be of potential benefit to accelerate bone healing, especially in defects caused by atrophic nonunion and avascular necrosis of the femoral head.

Imaging accretion sources and circumbinary disks in young brown dwarfs

NASA Astrophysics Data System (ADS)

Reiners, Ansgar

2010-09-01

We propose to obtain deep WFC3/UVIS imaging observations of two accreting, nearby, young brown dwarf binaries. The first, 2M1207, is a brown dwarf with a planetary mass companion that became a benchmark in low-mass star formation and low-mass evolutionary models. The second, 2M0041, is a nearby young brown dwarf with clear evidence for accretion, but its space motion suggests a slightly higher age than the canonical accretion lifetime of 5-10 Myr. It has recently been discovered to be a binary and is likely to become a second benchmark object in this field. With narrow band images centered on the Halpha line that is indicative of accretion, we aim to determine the accretion ratio between the two components in each system. Halpha was observed in both systems but so far not spatially resolved. In particular, we want to search for accretion in the planetary mass companion of 2M1207. The evidence for accretion in 2M0041 and the possibility that it is in fact older than 10Myr suggests that the accretion lifetime is longer in brown dwarfs than in stars, and in particular that it is longer in brown dwarf binaries. Accretion could be sustained for a longer time if the accreting material is replenished by a circumbinary disk that might exist in both systems. We propose deep WFC/UVIS observations in the optical to search for circumbinary disks, similar to the famous disk around the binary TTauri system GG Tau.

A Three-dimensional Simulation of a Magnetized Accretion Disk: Fast Funnel Accretion onto a Weakly Magnetized Star

NASA Astrophysics Data System (ADS)

Takasao, Shinsuke; Tomida, Kengo; Iwasaki, Kazunari; Suzuki, Takeru K.

2018-04-01

We present the results of a global, three-dimensional magnetohydrodynamics simulation of an accretion disk with a rotating, weakly magnetized central star. The disk is threaded by a weak, large-scale poloidal magnetic field, and the central star has no strong stellar magnetosphere initially. Our simulation investigates the structure of the accretion flows from a turbulent accretion disk onto the star. The simulation reveals that fast accretion onto the star at high latitudes occurs even without a stellar magnetosphere. We find that the failed disk wind becomes the fast, high-latitude accretion as a result of angular momentum exchange mediated by magnetic fields well above the disk, where the Lorentz force that decelerates the rotational motion of gas can be comparable to the centrifugal force. Unlike the classical magnetospheric accretion scenario, fast accretion streams are not guided by magnetic fields of the stellar magnetosphere. Nevertheless, the accretion velocity reaches the free-fall velocity at the stellar surface due to the efficient angular momentum loss at a distant place from the star. This study provides a possible explanation why Herbig Ae/Be stars whose magnetic fields are generally not strong enough to form magnetospheres also show indications of fast accretion. A magnetically driven jet is not formed from the disk in our model. The differential rotation cannot generate sufficiently strong magnetic fields for the jet acceleration because the Parker instability interrupts the field amplification.

Does a novel school-based physical activity model benefit femoral neck bone strength in pre- and early pubertal children?

PubMed

Macdonald, H M; Kontulainen, S A; Petit, M A; Beck, T J; Khan, K M; McKay, H A

2008-10-01

The effects of physical activity on bone strength acquisition during growth are not well understood. In our cluster randomized trial, we found that participation in a novel school-based physical activity program enhanced bone strength acquisition and bone mass accrual by 2-5% at the femoral neck in girls; however, these benefits depended on teacher compliance with intervention delivery. Our intervention also enhanced bone mass accrual by 2-4% at the lumbar spine and total body in boys. We investigated the effects of a novel school-based physical activity program on femoral neck (FN) bone strength and mass in children aged 9-11 yrs. We used hip structure analysis to compare 16-month changes in FN bone strength, geometry and bone mineral content (BMC) between 293 children who participated in Action Schools! BC (AS! BC) and 117 controls. We assessed proximal femur (PF), lumbar spine (LS) and total body (TB) BMC using DXA. We compared change in bone outcomes between groups using linear regression accounting for the random school effect and select covariates. Change in FN strength (section modulus, Z), cross-sectional area (CSA), subperiosteal width and BMC was similar between control and intervention boys, but intervention boys had greater gains in BMC at the LS (+2.7%, p = 0.05) and TB (+1.7%, p = 0.03) than controls. For girls, change in FN-Z tended to be greater (+3.5%, p = 0.1) for intervention girls than controls. The difference in change increased to 5.4% (p = 0.05) in a per-protocol analysis that included girls whose teachers reported 80% compliance. AS! BC benefits bone strength and mass in school-aged children; however, our findings highlight the importance of accounting for teacher compliance in classroom-based physical activity interventions.

C-Mpl is expressed on osteoblasts and osteoclasts and is important in regulating skeletal homeostasis

PubMed Central

Meijome, Tomas E.; Baughman, Jenna T.; Hooker, R. Adam; Cheng, Ying-Hua; Ciovacco, Wendy A.; Balamohan, Sanjeev M.; Srinivasan, Trishya L.; Chitteti, Brahmananda R.; Eleniste, Pierre P.; Horowitz, Mark C.; Srour, Edward F.; Bruzzaniti, Angela; Fuchs, Robyn K.; Kacena, Melissa A.

2016-01-01

C-Mpl is the receptor for thrombopoietin (TPO), the main megakaryocyte (MK) growth factor, and c-Mpl is believed to be expressed on cells of the hematopoietic lineage. As MKs have been shown to enhance bone formation, it may be expected that mice in which c-Mpl was globally knocked out (c-Mpl−/− mice) would have decreased bone mass because they have fewer MKs. Instead, c-Mpl−/− mice have a higher bone mass than WT controls. Using c-Mpl−/− mice we investigated the basis for this discrepancy and discovered that c-Mpl is expressed on both osteoblasts (OBs) and osteoclasts (OCs), an unexpected finding that prompted us to examine further how c-Mpl regulates bone. Static and dynamic bone histomorphometry parameters suggest that c-Mpl deficiency results in a high bone turnover state with a net gain in bone volume. In vitro, a higher percentage of c-Mpl−/− OBs were in active phases of the cell cycle, leading to an increased number of OBs. No difference in OB differentiation was observed in vitro as examined by real-time PCR and functional assays. In co-culture systems, which allow for the interaction between OBs and OC progenitors, c-Mpl−/− OBs enhanced osteoclastogenesis. Two of the major signaling pathways by which OBs regulate osteoclastogenesis, MCSF/OPG/RANKL and EphrinB2-EphB2/B4, were unaffected in c-Mpl−/− OBs. These data provide new findings for the role of MKs and c-Mpl expression in bone and may provide insight into the homeostatic regulation of bone mass as well as bone loss diseases such as osteoporosis. PMID:26375403

Clinical Importance of Temporal Bone Features for the Efficacy of Contrast-Enhanced Sonothrombolysis: a Retrospective Analysis of the NOR-SASS Trial.

PubMed

Novotny, Vojtech; Nacu, Aliona; Kvistad, Christopher E; Fromm, Annette; Neckelmann, Gesche F; Khanevski, Andrej N; Tobro, Haakon; Waje-Andreassen, Ulrike; Naess, Halvor; Thomassen, Lars; Logallo, Nicola

2017-11-08

Contrast-enhanced sonothrombolysis (CEST) seems to be a safe and promising treatment in acute ischemic stroke. It remains unknown if temporal bone features may influence the efficacy of CEST. We investigated the association between different temporal bone features on admission computed tomography (CT) scan and the outcome in acute ischemic stroke patients included in the randomized Norwegian Sonothrombolysis in Acute Stroke Study (NOR-SASS). Patients diagnosed as stroke mimics and those with infratentorial stroke or with incorrect insonation were excluded. We retrospectively assessed temporal bone heterogeneity (presence of diploë), diploë ratio, thickness, and density on admission CT scans. National institute of Health Stroke Scale (NIHSS) at 24 h and modified Rankin Scale (mRS) at 3 months were correlated with CT findings both in CEST and sham CEST patients. A total of 99 patients were included of which 52 were assigned to CEST and 47 to sham CEST. Approximately 20% patients had a heterogeneous temporal bone in both the CEST and sham CEST group. All temporal bone CT features studied were associated with female sex. In the CEST group, temporal bone heterogeneity (p = 0.006) and higher temporal bone diploë ratio (p = 0.002) were associated with higher NIHSS at 24 h. There was no association between temporal bone features and mRS at 3 months. Approximately 20% of acute ischemic stroke patients have heterogeneous temporal bone and may be resistant to standard 2-MHz transcranial Doppler ultrasound treatment. Sonothrombolysis resistance may easily be predicted by admission CT for better selection.

Hydroxyapatite nanorod and microsphere functionalized with bioactive lactoferrin as a new biomaterial for enhancement bone regeneration.

PubMed

Shi, Pujie; Wang, Qun; Yu, Cuiping; Fan, Fengjiao; Liu, Meng; Tu, Maolin; Lu, Weihong; Du, Ming

2017-07-01

Lactoferrin (LF) has been recently recognized as a promising new novel bone growth factor for the beneficial effects on bone cells and promotion of bone growth. Currently, it has been attracted wide attention in bone regeneration as functional food additives or a potential bioactive protein in bone tissue engineering. The present study investigated the possibility that hydroxyapatite (HAP) particles, a widely used bone substitute material for high biocompatibility and osteoconductivity, functionalized with lactoferrin as a composite material are applied to bone tissue engineering. Two kinds of hydroxyapatite samples with different sizes, including nanorods and microspheres particles, were functionalized with lactoferrin molecules, respectively. A detailed characterization of as-prepared HAP-LF complex is presented, combining thermal gravimetric analysis (TGA) and Fourier Transform Infrared Spectroscopy (FT-IR). Zeta potential and the analysis of electrostatic surface potential of lactoferrin were carried to reveal the mechanism of adsorption. The effects of HAP-LF complex on MC3T3-E1 osteoblast proliferation and morphology were systematically evaluated at different culture time. Interestingly, results showed that cell viability of HAP-LF group was significantly higher than HAP group indicating that the HAP-LF can improve the biocompatibility of HAP, which mainly originated from a combination of HAP-LF interaction. These results indicated that hydroxyapatite particles can work as a controlled releasing carrier of lactoferrin successfully, and lactoferrin showed better potentiality on using in the field of bone regeneration by coupling with hydroxyapatite. This study would provide a new biomaterial and might offer a new insight for enhancement of bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

PubMed

Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

2017-09-01

In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

Anabolic and Antiresorptive Modulation of Bone Homeostasis by the Epigenetic Modulator Sulforaphane, a Naturally Occurring Isothiocyanate*

PubMed Central

Thaler, Roman; Maurizi, Antonio; Roschger, Paul; Sturmlechner, Ines; Khani, Farzaneh; Spitzer, Silvia; Rumpler, Monika; Zwerina, Jochen; Karlic, Heidrun; Dudakovic, Amel; Klaushofer, Klaus; Teti, Anna; Rucci, Nadia; Varga, Franz; van Wijnen, Andre J.

2016-01-01

Bone degenerative pathologies like osteoporosis may be initiated by age-related shifts in anabolic and catabolic responses that control bone homeostasis. Here we show that sulforaphane (SFN), a naturally occurring isothiocyanate, promotes osteoblast differentiation by epigenetic mechanisms. SFN enhances active DNA demethylation via Tet1 and Tet2 and promotes preosteoblast differentiation by enhancing extracellular matrix mineralization and the expression of osteoblastic markers (Runx2, Col1a1, Bglap2, Sp7, Atf4, and Alpl). SFN decreases the expression of the osteoclast activator receptor activator of nuclear factor-κB ligand (RANKL) in osteocytes and mouse calvarial explants and preferentially induces apoptosis in preosteoclastic cells via up-regulation of the Tet1/Fas/Caspase 8 and Caspase 3/7 pathway. These mechanistic effects correlate with higher bone volume (∼20%) in both normal and ovariectomized mice treated with SFN for 5 weeks compared with untreated mice as determined by microcomputed tomography. This effect is due to a higher trabecular number in these mice. Importantly, no shifts in mineral density distribution are observed upon SFN treatment as measured by quantitative backscattered electron imaging. Our data indicate that the food-derived compound SFN epigenetically stimulates osteoblast activity and diminishes osteoclast bone resorption, shifting the balance of bone homeostasis and favoring bone acquisition and/or mitigation of bone resorption in vivo. Thus, SFN is a member of a new class of epigenetic compounds that could be considered for novel strategies to counteract osteoporosis. PMID:26757819

Integration of High-resolution Data for Temporal Bone Surgical Simulations

PubMed Central

Wiet, Gregory J.; Stredney, Don; Powell, Kimerly; Hittle, Brad; Kerwin, Thomas

2016-01-01

Purpose To report on the state of the art in obtaining high-resolution 3D data of the microanatomy of the temporal bone and to process that data for integration into a surgical simulator. Specifically, we report on our experience in this area and discuss the issues involved to further the field. Data Sources Current temporal bone image acquisition and image processing established in the literature as well as in house methodological development. Review Methods We reviewed the current English literature for the techniques used in computer-based temporal bone simulation systems to obtain and process anatomical data for use within the simulation. Search terms included “temporal bone simulation, surgical simulation, temporal bone.” Articles were chosen and reviewed that directly addressed data acquisition and processing/segmentation and enhancement with emphasis given to computer based systems. We present the results from this review in relationship to our approach. Conclusions High-resolution CT imaging (≤100μm voxel resolution), along with unique image processing and rendering algorithms, and structure specific enhancement are needed for high-level training and assessment using temporal bone surgical simulators. Higher resolution clinical scanning and automated processes that run in efficient time frames are needed before these systems can routinely support pre-surgical planning. Additionally, protocols such as that provided in this manuscript need to be disseminated to increase the number and variety of virtual temporal bones available for training and performance assessment. PMID:26762105

Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism

PubMed Central

Chen, Julia C.; Hoey, David A.; Chua, Mardonn; Bellon, Raymond; Jacobs, Christopher R.

2016-01-01

It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitment in vitro. In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for the first time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cells in vivo. Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitment in vivo and that the primary cilium contributes to this process.—Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism. PMID:26675708

In vitro characterization of MG-63 osteoblast-like cells cultured on organic-inorganic lyophilized gelatin sponges for early bone healing.

PubMed

Rodriguez, Isaac A; Saxena, Gunjan; Hixon, Katherine R; Sell, Scott A; Bowlin, Gary L

2016-08-01

The development of three-dimensional porous scaffolds with enhanced osteogenic and angiogenic potential would be beneficial for inducing early-stage bone regeneration. Previous studies have demonstrated the advantages of mineralized and nonmineralized acellular 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) cross-linked gelatin sponges enhanced with preparations rich in growth factors, hydroxyapatite, and chitin whiskers. In this study, those same scaffolds were mineralized and dynamically seeded with MG-63 cells. Cell proliferation, protein/cytokine secretion, and compressive mechanical properties of scaffolds were evaluated. It was found that mineralization and the addition of growth factors increased cell proliferation compared to gelatin controls. Cells on all scaffolds responded in an appropriate bone regenerative fashion as shown through osteocalcin secretion and little to no secretion of bone resorbing markers. However, compressive mechanical properties of cellularized scaffolds were not significantly different from acellular scaffolds. The combined results of increased cellular attachment, infiltration, and bone regenerative protein/cytokine secretion on scaffolds support the need for the addition of a bone-like mineral surface. Cellularized scaffolds containing growth factors reported similar advantages and mechanical values in the range of native tissues present in the early stages of bone healing. These results suggest that the developed composite sponges exhibited cellular responses and mechanical properties appropriate for promoting early bone healing in various applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2011-2019, 2016. © 2016 Wiley Periodicals, Inc.

Helium shell flashes and evolution of accreting white dwarfs

NASA Astrophysics Data System (ADS)

Fujimoto, M. Y.; Sugimoto, D.

1982-06-01

The evolution of accreting white dwarfs is investigated from the onset of accretion through the helium shell flash. Properties of the helium shell flashes are studied by means of a generalized theory of shell flash and by numerical computations, and it is found that the shell flash grows up to the strength of a supernova explosion when the mass of the helium zone is large enough on a massive white dwarf. Although accretion onto a hot white dwarf causes a weaker shell flash than those onto cool ones, a strong tendency exists for the strength to be determined mainly by the accretion rate. For fast accretion, the shell flashes are weak and triggered recurrently, while for slow accretion the helium shell flash, once triggered, develops into a detonation supernova.

Unveiling slim accretion disc in AGN through X-ray and Infrared observations

NASA Astrophysics Data System (ADS)

Castelló-Mor, Núria; Kaspi, Shai; Netzer, Hagai; Du, Pu; Hu, Chen; Ho, Luis C.; Bai, Jin-Ming; Bian, Wei-Hao; Yuan, Ye-Fei; Wang, Jian-Min

2017-05-01

In this work, which is a continuation of Castelló-Mor et al., we present new X-ray and infrared (IR) data for a sample of active galactic nuclei (AGN) covering a wide range in Eddington ratio over a small luminosity range. In particular, we rigorously explore the dependence of the optical-to-X-ray spectral index αOX and the IR-to-optical spectral index on the dimensionless accretion rate, \\dot{M} = \\dot{m}/η, where \\dot{m} = LAGN/LEdd and η is the mass-to-radiation conversion efficiency, in low- and high-accretion rate sources. We find that the spectral energy distribution (SED) of the faster accreting sources is surprisingly similar to those from the comparison sample of sources with lower accretion rate. In particular: (I) The optical-to-UV AGN SED of slow and fast accreting AGN can be fitted with thin accretion disc (AD) models. (II) The value of αOX is very similar in slow and fast accreting systems up to a dimensionless accretion rate \\dot{M}c ˜ 10. We only find a correlation between αOX and \\dot{M} for sources with \\dot{M} > \\dot{M}c. In such cases, the faster accreting sources appear to have systematically larger αOX values. (III) We also find that the torus in the faster accreting systems seems to be less efficient in reprocessing the primary AGN radiation having lower IR-to-optical spectral slopes. These findings, failing to recover the predicted differences between the SEDs of slim and thin ADs within the observed spectral window, suggest that additional physical processes or very special geometry act to reduce the extreme-UV radiation in fast accreting AGN. This may be related to photon trapping, strong winds and perhaps other yet unknown physical processes.

Supermassive Black Holes with High Accretion Rates in Active Galactic Nuclei. IX. 10 New Observations of Reverberation Mapping and Shortened Hβ Lags

NASA Astrophysics Data System (ADS)

Du, Pu; Zhang, Zhi-Xiang; Wang, Kai; Huang, Ying-Ke; Zhang, Yue; Lu, Kai-Xing; Hu, Chen; Li, Yan-Rong; Bai, Jin-Ming; Bian, Wei-Hao; Yuan, Ye-Fei; Ho, Luis C.; Wang, Jian-Min; SEAMBH collaboration

2018-03-01

As one paper in a series reporting on a large reverberation mapping campaign of super-Eddington accreting massive black holes (SEAMBHs) in active galactic nuclei (AGNs), we present the results of 10 SEAMBHs monitored spectroscopically during 2015–2017. Six of them are observed for the first time, and have generally higher 5100 Å luminosities than the SEAMBHs monitored in our campaign from 2012 to 2015; the remaining four are repeat observations to check if their previous lags change. Similar to the previous SEAMBHs, the Hβ time lags of the newly observed objects are shorter than the values predicted by the canonical R Hβ –L 5100 relation of sub-Eddington AGNs, by factors of ∼2–6, depending on the accretion rate. The four previously observed objects have lags consistent with previous measurements. We provide linear regressions for the R Hβ –L 5100 relation, solely for the SEAMBH sample and for low-accretion AGNs. We find that the relative strength of Fe II and the profile of the Hβ emission line can be used as proxies of accretion rate, showing that the shortening of Hβ lags depends on accretion rates. The recent SDSS-RM discovery of shortened Hβ lags in AGNs with low accretion rates provides compelling evidence for retrograde accretion onto the black hole. These evidences show that the canonical R Hβ –L 5100 relation holds only in AGNs with moderate accretion rates. At low accretion rates, it should be revised to include the effects of black hole spin, whereas the accretion rate itself becomes a key factor in the regime of high accretion rates.

Magnetically gated accretion in an accreting ‘non-magnetic’ white dwarf

NASA Astrophysics Data System (ADS)

Scaringi, S.; Maccarone, T. J.; D’Angelo, C.; Knigge, C.; Groot, P. J.

2017-12-01

White dwarfs are often found in binary systems with orbital periods ranging from tens of minutes to hours in which they can accrete gas from their companion stars. In about 15 per cent of these binaries, the magnetic field of the white dwarf is strong enough (at 106 gauss or more) to channel the accreted matter along field lines onto the magnetic poles. The remaining systems are referred to as ‘non-magnetic’, because until now there has been no evidence that they have a magnetic field that is strong enough to affect the accretion dynamics. Here we report an analysis of archival optical observations of the ‘non-magnetic’ accreting white dwarf in the binary system MV Lyrae, whose light curve displays quasi-periodic bursts of about 30 minutes duration roughly every 2 hours. The timescale and amplitude of these bursts indicate the presence of an unstable, magnetically regulated accretion mode, which in turn implies the existence of magnetically gated accretion, in which disk material builds up around the magnetospheric boundary (at the co-rotation radius) and then accretes onto the white dwarf, producing bursts powered by the release of gravitational potential energy. We infer a surface magnetic field strength for the white dwarf in MV Lyrae of between 2 × 104 gauss and 1 × 105 gauss, too low to be detectable by other current methods. Our discovery provides a new way of studying the strength and evolution of magnetic fields in accreting white dwarfs and extends the connections between accretion onto white dwarfs, young stellar objects and neutron stars, for which similar magnetically gated accretion cycles have been identified.

Magnetically gated accretion in an accreting 'non-magnetic' white dwarf.

PubMed

Scaringi, S; Maccarone, T J; D'Angelo, C; Knigge, C; Groot, P J

2017-12-13

White dwarfs are often found in binary systems with orbital periods ranging from tens of minutes to hours in which they can accrete gas from their companion stars. In about 15 per cent of these binaries, the magnetic field of the white dwarf is strong enough (at 10 6 gauss or more) to channel the accreted matter along field lines onto the magnetic poles. The remaining systems are referred to as 'non-magnetic', because until now there has been no evidence that they have a magnetic field that is strong enough to affect the accretion dynamics. Here we report an analysis of archival optical observations of the 'non-magnetic' accreting white dwarf in the binary system MV Lyrae, whose light curve displays quasi-periodic bursts of about 30 minutes duration roughly every 2 hours. The timescale and amplitude of these bursts indicate the presence of an unstable, magnetically regulated accretion mode, which in turn implies the existence of magnetically gated accretion, in which disk material builds up around the magnetospheric boundary (at the co-rotation radius) and then accretes onto the white dwarf, producing bursts powered by the release of gravitational potential energy. We infer a surface magnetic field strength for the white dwarf in MV Lyrae of between 2 × 10 4 gauss and 1 × 10 5 gauss, too low to be detectable by other current methods. Our discovery provides a new way of studying the strength and evolution of magnetic fields in accreting white dwarfs and extends the connections between accretion onto white dwarfs, young stellar objects and neutron stars, for which similar magnetically gated accretion cycles have been identified.

Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

PubMed Central

Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

2015-01-01

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. PMID:26125501

MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7 Promotes Osteoblast Differentiation and Bone Formation.

PubMed

Zhang, Yan; Yin, Chong; Hu, Lifang; Chen, Zhihao; Zhao, Fan; Li, Dijie; Ma, Jianhua; Ma, Xiaoli; Su, Peihong; Qiu, Wuxia; Yang, Chaofei; Wang, Pai; Li, Siyu; Zhang, Ge; Wang, Liping; Qian, Airong; Xian, Cory J

2018-02-01

Microtubule actin crosslinking factor 1 (MACF1) is a large spectraplakin protein known to have crucial roles in regulating cytoskeletal dynamics, cell migration, growth, and differentiation. However, its role and action mechanism in bone remain unclear. The present study investigated optimal conditions for effective transfection of the large plasmid PEGFP-C1A-ACF7 (∼21 kbp) containing full-length human MACF1 cDNA, as well as the potential role of MACF1 in bone formation. To enhance MACF1 expression, the plasmid was transfected into osteogenic cells by electroporation in vitro and into mouse calvaria with nanoparticles. Then, transfection efficiency, osteogenic marker expression, calvarial thickness, and bone formation were analyzed. Notably, MACF1 overexpression triggered a drastic increase in osteogenic gene expression, alkaline phosphatase activity, and matrix mineralization in vitro. Mouse calvarial thickness, mineral apposition rate, and osteogenic marker protein expression were significantly enhanced by local transfection. In addition, MACF1 overexpression promoted β-catenin expression and signaling. In conclusion, MACF1 overexpression by transfecting the large plasmid containing full-length MACF1 cDNA promotes osteoblast differentiation and bone formation via β-catenin signaling. Current data will provide useful experimental parameters for the transfection of large plasmids and a novel strategy based on promoting bone formation for prevention and therapy of bone disorders.