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Sample records for lamellar bone formation

  1. Antagonizing the ?v?3 Integrin Inhibits Angiogenesis and Impairs Woven but Not Lamellar Bone Formation Induced by Mechanical Loading

    PubMed Central

    Tomlinson, Ryan E.; Schmieder, Anne H.; Quirk, James D.; Lanza, Gregory M.; Silva, Matthew J.

    2015-01-01

    Angiogenesis and osteogenesis are critically linked, though the role of angiogenesis is not well understood in osteogenic mechanical loading. In this study, either damaging or non-damaging cyclic axial compression was used to generate woven bone formation (WBF) or lamellar bone formation (LBF), respectively, at the mid-diaphysis of the adult rat forelimb. ?v?3 integrin targeted nanoparticles or vehicle was injected intravenously following mechanical loading. ?3 integrin subunit expression on vasculature was maximal 7 days after damaging mechanical loading, but was still robustly expressed 14 days after loading. Accordingly, targeted nanoparticle delivery in WBF loaded limbs was increased compared to non-loaded limbs. Vascularity was dramatically increased after WBF loading (+700% on day 14) and modestly increased after LBF loading (+50% on day 14). This increase in vascularity was inhibited by nanoparticle treatment in both WBF and LBF loaded limbs at days 7 and 14 after loading. Decreased vascularity led to diminished woven, but not lamellar, bone formation. Decreased woven bone formation resulted in impaired structural properties of the skeletal repair, particularly in post-yield behavior. These results demonstrate that ?v?3 integrin mediated angiogenesis is critical for recovering fracture resistance following bone injury, but is not required for bone modeling after modest mechanical strain. PMID:24644077

  2. Trabecular packet-level lamellar density patterns differ by fracture status and bone formation rate in white females.

    PubMed

    Ciarelli, Traci E; Tjhia, Crystal; Rao, D Sudhaker; Qiu, Shijing; Parfitt, A Michael; Fyhrie, David P

    2009-11-01

    Spatial patterns of mineralization for human iliac crest cancellous bone were measured from images obtained by quantitative backscattered electron microscopy. Biopsies collected from vertebral fracture patients and healthy individuals with high or low bone formation rate (BFR(s)) were examined (fracture/low BFR(s): N=12, fracture/high BFR(s): N=10, normal/low BFR(s): N=12, normal/high BFR(s): N=15). 20 by 20 pixel square areas or smaller were sampled from superficial and deep remodeling packets. Mean (Z(mean)) and standard deviation (SD) of mineralization were measured, and coefficients of variation (CV=SD/Z(mean)) were calculated. Fast Fourier transform analysis was used to quantify the distribution of the mineral in the packets. "FFT_ratio" was defined as the ratio magnitude of the principal spatial frequency to the average atomic number density. A higher FFT_ratio occurred in specimens with more pronounced alternating layers of light and dark as visible in the backscattered electron image, which was defined as lamellar patterning. Two-way ANOVA revealed that the coefficients of variation of mineralization for both superficial and deep packets were significantly lower in fracture patients than in normal individuals. However, the interaction between turnover rate and group (fracture/non-fracture) indicated that the difference in packet CV occurred among the low turnover individuals and not among those with high turnover. Mean mineralization levels and CV between deep and superficial packets were highly correlated. Regressions of packet CV of mineralization and FFT_ratio were highly significant (p<0.001) for all packets pooled and for packets divided by group (fracture/normal). However, analyses of packet CV and FFT_ratio by individual were variable (R(2) from 0.00338 to 0.700). Packet-level mineralization variability may be associated with fracture toughness, and fracture patients had less variable packet-level mineralization. The result that the packet CV varied significantly between fracture and non-fracture individuals with low turnover suggests that for low turnover subjects without fracture, high variability in mineralization may have a protective effect. In high turnover patients, the accelerated turnover may prevent the lamellar variability from developing over time. Strong correlations between CV and Z(mean) for both superficial and deep packets imply that newly formed bone is created similarly to older bone within an individual. Fourier transform results show that the mineralization variability found within packets is associated with lamellar patterning. Lamellar structure has been hypothesized to guide microcrack propagation in order to optimize bone strength and toughness. Osteoporotics with fracture had less pronounced lamellation than healthy normals and may be more prone to fracture. PMID:19615479

  3. Structural orientation dependent sub-lamellar bone mechanics.

    PubMed

    Jimenez-Palomar, Ines; Shipov, Anna; Shahar, Ron; Barber, Asa H

    2015-12-01

    The lamellar unit is a critical component in defining the overall mechanical properties of bone. In this paper, micro-beams of bone with dimensions comparable to the lamellar unit were fabricated using focused ion beam (FIB) microscopy and mechanically tested in bending to failure using atomic force microscopy (AFM). A variation in the mechanical properties, including elastic modulus, strength and work to fracture of the micro-beams was observed and related to the collagen fibril orientation inferred from back-scattered scanning electron microscopy (SEM) imaging. Established mechanical models were further applied to describe the relationship between collagen fibril orientation and mechanical behaviour of the lamellar unit. Our results highlight the ability to measure mechanical properties of discrete bone volumes directly and correlate with structural orientation of collagen fibrils. PMID:25816782

  4. Formation Of Nano Layered Lamellar Structure In a Processed ?-TiAl Based Alloy

    NASA Astrophysics Data System (ADS)

    Heshmati-Manesh, S.; Shakoorian, H.; Armaki, H. Ghassemi; Ahmadabadi, M. Nili

    2009-06-01

    In this research, microstructures of an intermetallic alloy based on ?-TiAl has been investigated by optical and transmission electron microscopy. Samples of Ti-47Al-2Cr alloy were subjected to either a cyclic heat treatment or thermomechanical treatment with the aim of microstructural refinement. In both cases it was found that very fine lamellar structure with an interlamellar spacing in the nano scale is formed. Upon cyclic heat treatment, nano layers of ?2 and ? ordered intermetallic phases were either formed during rapid cooling cycle in competition with massive structure formation, or formed as secondary lamellar structure during final stages of cyclic heat treatment. Also, TEM observations in hot forged specimens with initial lamellar structure revealed that micro twins form during the deformation within lamellar structure with twinning plates parallel to lamellar interfaces. Concurrent dynamic recrystallisation results in a nano layered structure with an interlamellar spacing of less than 100 nm.

  5. Microfibril orientation dominates the microelastic properties of human bone tissue at the lamellar length scale.

    PubMed

    Granke, Mathilde; Gourrier, Aurélien; Rupin, Fabienne; Raum, Kay; Peyrin, Françoise; Burghammer, Manfred; Saïed, Amena; Laugier, Pascal

    2013-01-01

    The elastic properties of bone tissue determine the biomechanical behavior of bone at the organ level. It is now widely accepted that the nanoscale structure of bone plays an important role to determine the elastic properties at the tissue level. Hence, in addition to the mineral density, the structure and organization of the mineral nanoparticles and of the collagen microfibrils appear as potential key factors governing the elasticity. Many studies exist on the role of the organization of collagen microfibril and mineral nanocrystals in strongly remodeled bone. However, there is no direct experimental proof to support the theoretical calculations. Here, we provide such evidence through a novel approach combining several high resolution imaging techniques: scanning acoustic microscopy, quantitative scanning small-Angle X-ray scattering imaging and synchrotron radiation computed microtomography. We find that the periodic modulations of elasticity across osteonal bone are essentially determined by the orientation of the mineral nanoparticles and to a lesser extent only by the particle size and density. Based on the strong correlation between the orientation of the mineral nanoparticles and the collagen molecules, we conclude that the microfibril orientation is the main determinant of the observed undulations of microelastic properties in regions of constant mineralization in osteonal lamellar bone. This multimodal approach could be applied to a much broader range of fibrous biological materials for the purpose of biomimetic technologies. PMID:23472132

  6. Microfibril Orientation Dominates the Microelastic Properties of Human Bone Tissue at the Lamellar Length Scale

    PubMed Central

    Rupin, Fabienne; Raum, Kay; Peyrin, Françoise; Burghammer, Manfred; Saïed, Amena; Laugier, Pascal

    2013-01-01

    The elastic properties of bone tissue determine the biomechanical behavior of bone at the organ level. It is now widely accepted that the nanoscale structure of bone plays an important role to determine the elastic properties at the tissue level. Hence, in addition to the mineral density, the structure and organization of the mineral nanoparticles and of the collagen microfibrils appear as potential key factors governing the elasticity. Many studies exist on the role of the organization of collagen microfibril and mineral nanocrystals in strongly remodeled bone. However, there is no direct experimental proof to support the theoretical calculations. Here, we provide such evidence through a novel approach combining several high resolution imaging techniques: scanning acoustic microscopy, quantitative scanning small-Angle X-ray scattering imaging and synchrotron radiation computed microtomography. We find that the periodic modulations of elasticity across osteonal bone are essentially determined by the orientation of the mineral nanoparticles and to a lesser extent only by the particle size and density. Based on the strong correlation between the orientation of the mineral nanoparticles and the collagen molecules, we conclude that the microfibril orientation is the main determinant of the observed undulations of microelastic properties in regions of constant mineralization in osteonal lamellar bone. This multimodal approach could be applied to a much broader range of fibrous biological materials for the purpose of biomimetic technologies. PMID:23472132

  7. Peripheral Leptin Regulates Bone Formation

    PubMed Central

    Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

    2012-01-01

    Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

  8. Bone formation: roles of genistein and daidzein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone remodeling consists of a balance between bone formation by osteoblasts and bone resorption by osteoclasts. Osteoporosis is the result of increased bone resorption and decreased bone formation causing a decreased bone mass density, loss of bone microarchitecture, and an increased risk of fractu...

  9. Spreading of fibroblasts in medium containing cytochalasin B: formation of lamellar cytoplasm as a combination of several functional different processes.

    PubMed

    Bliokh, Z L; Domnina, L V; Ivanova, O Y; Pletjushkina, O Y; Svitkina, T M; Smolyaninov, V A; Vasiliev, J M; Gelfand, I M

    1980-10-01

    Normal cultured mouse fibroblasts spreading on solid substrate extend and attach numerous pseudopods; lamellar cytoplasm is eventually formed from the attached pseudopods. Fibroblasts spreading in the presence of cytochasin B (CB) from de novo a system of arbor-like branched processes rather than lamellar cytoplasm. The growing and fully formed arbor-like processes, in contrast to normal lamellar cytoplasm, have low contractility and are unable to clear patched concanavalin A receptors from their surfaces; their attachement sites are not associated with microfilament bundles. The cells spreading in medium containing CB and Colcemid do not form well-organized branched structures but extend and attach numerous unstable pseudopods. It is suggested that normal formation of lamellar cytoplasm can be regarded as a combination of several functionally different processes: (a) of rudimentary pseudopodial reactions resistant to CB and Colcemid; (b) of CB-sensitive lamellization; and (c) of Colcemid-sensitive stabilization. PMID:6934523

  10. Periodic Formation/Breakdown of Lamellar Aggregates with Anionic Cyanobiphenyl Surfactants.

    PubMed

    Sagisaka, Masanobu; Fujita, Yayoi; Nakanishi, Yusuke; Takahashi, Hisayuki; Tsuyoshi, Narumi; James, Craig; Yoshizawa, Atsushi; Mohamed, Azmi; Guittard, Frédéric; Eastoe, Julian

    2015-12-01

    This study reports unusual behavior of aqueous-phase lamellar aggregates with a new class of hybrid surfactant, CB-B2ES, having mesogenic units {6-[4-(4-cyanophenyl)phenyloxy]hexyl} and temperature-sensitive oxyethylated (butoxyethoxyethyl) tails. These tails are poorly miscible and likely to microsegregate if the surfactant molecules assemble. Lamellar aggregates appear at CB-B2ES concentrations higher than 5 wt % and were found to undergo repeat formation/breakdown periodically at 30 °C, with an average domain lifetime of ?10 s. To investigate effects of the temperature-sensitive oxyethylene units on the hydrophilic/lipophilic balance (HLB) of the CB-B2ES bilayers, a fluorescence probe 1-pyrene-carboxaldehide was solubilized in the mixtures to sense the micro-environmental polarities. Fluorimetric measurements suggested that the polarity of CB-B2ES bilayers is very similar to that of the non-ethoxylated CB-B2ES analogue at high temperatures (?65 °C). However, for CB-B2ES, polarity increased with a decreasing temperature, in contrast with the small decrease in polarity observed for analogous non-ethoxylated bilayers. This is consistent with increased hydration of the oxyethylene units in CB-B2ES bilayers at low temperatures. The periodic formation/breakdown and cooling-induced hydrophilicity of the CB-B2ES lamellar aggregates did not appear in the non-hybrid and/or non-ethoxylated surfactant systems. Therefore, the combination of two unsymmetrical tails, one containing oxyethylene units and the other containing cyanobiphenyl terminal tips, must play an important role promoting this unusual behavior. PMID:26542352

  11. Recombinant human bone morphogenetic protein induces bone formation

    SciTech Connect

    Wang, E.A.; Rosen, V.; D'Alessandro, J.S.; Bauduy, M.; Cordes, P.; Harada, T.; Israel, D.I.; Hewick, R.M.; Kerns, K.M.; LaPan, P.; Luxenberg, D.P.; McQuaid, D.; Moutsatsos, I.K.; Nove, J.; Wozney, J.M. )

    1990-03-01

    The authors have purified and characterized active recombinant human bone morphogenetic protein (BMP) 2A. Implantation of the recombinant protein in rats showed that a single BMP can induce bone formation in vivo. A dose-response and time-course study using the rat ectopic bone formation assay revealed that implantation of 0.5-115 {mu}g of partially purified recombinant human BMP-2A resulted in cartilage by day 7 and bone formation by day 14. The time at which bone formation occurred was dependent on the amount of BMP-2A implanted; at high doses bone formation could be observed at 5 days. The cartilage- and bone-inductive activity of the recombinant BMP-2A is histologically indistinguishable from that of bone extracts. Thus, recombinant BMP-2A has therapeutic potential to promote de novo bone formation in humans.

  12. Mechanical behavior of osteoporotic bone at sub-lamellar length scales

    NASA Astrophysics Data System (ADS)

    Jimenez-Palomar, Ines; Shipov, Anna; Shahar, Ron; Barber, Asa

    2015-02-01

    Osteoporosis is a disease known to promote bone fragility but the effect on the mechanical properties of bone material, which is independent of geometric effects, is particularly unclear. To address this problem, micro-beams of osteoporotic bone were prepared using focused ion beam (FIB) microscopy and mechanically tested in compression using an atomic force microscope (AFM) while observing using in situ electron microscopy. This experimental approach was shown to be effective at measuring the subtle changes in the mechanical properties of bone material required to evaluate the effects of osteoporosis. Osteoporotic bone material was found to have lower elastic modulus and increased strain to failure when compared to healthy bone material, while the strength of osteoporotic and healthy bone was similar. A mechanism is suggested based on these results and previous literature that indicates degradation of the organic material in osteoporosis bone is responsible for resultant mechanical properties.

  13. Influence of the mineral staggering on the elastic properties of the mineralized collagen fibril in lamellar bone.

    PubMed

    Vercher-Martínez, Ana; Giner, Eugenio; Arango, Camila; Fuenmayor, F Javier

    2015-02-01

    In this work, a three-dimensional finite element model of the staggered distribution of the mineral within the mineralized collagen fibril has been developed to characterize the lamellar bone elastic behavior at the sub-micro length scale. Minerals have been assumed to be embedded in a collagen matrix, and different degrees of mineralization have been considered allowing the growth of platelet-shaped minerals both in the axial and the transverse directions of the fibril, through the variation of the lateral space between platelets. We provide numerical values and trends for all the elastic constants of the mineralized collagen fibril as a function of the volume fraction of mineral. In our results, we verify the high influence of the mineral overlapping on the mechanical response of the fibril and we highlight that the lateral distance between crystals is relevant to the mechanical behavior of the fibril and not only the mineral overlapping in the axial direction. PMID:25498297

  14. Hormonal and Local Regulation of Bone Formation.

    ERIC Educational Resources Information Center

    Canalis, Ernesto

    1985-01-01

    Reviews effects of hormones, systemic factors, and local regulators on bone formation. Identifies and explains the impact on bone growth of several hormones as well as the components of systemic and local systems. Concentrates on bone collagen and DNA synthesis. (Physicians may earn continuing education credit by completing an appended test). (ML)

  15. Formation of the lamellar structure in Group IA and IIID iron meteorites

    NASA Technical Reports Server (NTRS)

    Kowalik, J. A.; Williams, D. B.; Goldstein, J. I.

    1988-01-01

    Analytical EM, light microscopy, and electron microprobe analysis are used to study the lamellar plessite structure of Group IA and IIID iron meteorites. The alpha lamellae in IIID structures contained a compositional gradient from 6.1 + or - 0.7 wt pct Ni at the center of the alpha lamellae to 3.6 + or - 0.5 wt pct at the alpha/gamma interface. For the Group IA irons, compositions of 4 wt pct Ni in alpha and about 48 wt pct Ni in gamma are found. Convergent beam electron diffraction was used to characterize the orientation relations at the alpha/gamma interface in the lamellar regions of both Group IA and IIID. The phase transformations responsible for the observed lamellar structure in the IA and IIID chemical groups were also investigated.

  16. Bmp2 conditional knockout in osteoblasts and endothelial cells does not impair bone formation after injury or mechanical loading in adult mice.

    PubMed

    McBride-Gagyi, Sarah Howe; McKenzie, Jennifer A; Buettmann, Evan G; Gardner, Michael J; Silva, Matthew J

    2015-12-01

    Post-natal osteogenesis after mechanical trauma or stimulus occurs through either endochondral healing, intramembranous healing or lamellar bone formation. Bone morphogenetic protein 2 (BMP2) is up-regulated in each of these osteogenic processes and is expressed by a variety of cells including osteoblasts and vascular cells. It is known that genetic knockout of Bmp2 in all cells or in osteo-chondroprogenitor cells completely abrogates endochondral healing after full fracture. However, the importance of BMP2 from differentiated osteoblasts and endothelial cells is not known. Moreover, the importance of BMP2 in non-endochondral bone formation such as intramembranous healing or lamellar bone formation is not known. Using inducible and tissue-specific Cre-lox mediated targeting of Bmp2 in adult (10-24week old) mice, we assessed the role of BMP2 expression globally, by osteoblasts, and by vascular endothelial cells in endochondral healing, intramembranous healing and lamellar bone formation. These three osteogenic processes were modeled using full femur fracture, ulnar stress fracture, and ulnar non-damaging cyclic loading, respectively. Our results confirmed the requirement of BMP2 for endochondral fracture healing, as mice in which Bmp2 was knocked out in all cells prior to fracture failed to form a callus. Targeted deletion of Bmp2 in osteoblasts (osterix-expressing) or vascular endothelial cells (vascular endothelial cadherin-expressing) did not impact fracture healing in any way. Regarding non-endochondral bone formation, we found that BMP2 is largely dispensable for intramembranous bone formation after stress fracture and also not required for lamellar bone formation induced by mechanical loading. Taken together our results indicate that osteoblasts and endothelial cells are not a critical source of BMP2 in endochondral fracture healing, and that non-endochondral bone formation in the adult mouse is not as critically dependent on BMP2. PMID:26344756

  17. A three-scale finite element investigation into the effects of tissue mineralisation and lamellar organisation in human cortical and trabecular bone.

    PubMed

    Vaughan, T J; McCarthy, C T; McNamara, L M

    2012-08-01

    Bone is an exceptional material that is lightweight for efficient movement but also exhibits excellent strength and stiffness imparted by a composite material of organic proteins and mineral crystals that are intricately organised on many scales. Experimental and computational studies have sought to understand the role of bone composition and organisation in regulating the biomechanical behaviour of bone. However, due to the complex hierarchical arrangement of the constituent materials, the reported experimental values for the elastic modulus of trabecular and cortical tissue have conflicted greatly. Furthermore, finite element studies of bone have largely made the simplifying assumption that material behaviour was homogeneous or that tissue variability only occurred at the microscale, based on grey values from micro-CT scans. Thus, it remains that the precise role of nanoscale tissue constituents and microscale tissue organisation is not fully understood and more importantly that these have never been incorporated together to predict bone fracture or implant outcome in a multiscale finite element framework. In this paper, a three-scale finite element homogenisation scheme is presented which enables the prediction of homogenised effective properties of tissue level bone from its fundamental nanoscale constituents of hydroxyapatite mineral crystals and organic collagen proteins. Two independent homogenisation steps are performed on representative volume elements which describe the local morphological arrangement of both the nanostructural and microstructural levels. This three-scale homogenisation scheme predicts differences in the tissue level properties of bone as a function of mineral volume fraction, mineral aspect ratio and lamellar orientation. These parameters were chosen to lie within normal tissue ranges derived from experimental studies, and it was found that the predicted stiffness properties at the lamellar level correlate well with experimental nanoindentation results from cortical and trabecular bone. Furthermore, these studies show variations in mineral volume fraction, mineral crystal size and lamellar orientation could be responsible for previous discrepancies in experimental reports of tissue moduli. We propose that this novel multiscale modelling approach can provide a more accurate description of bone tissue properties in continuum/organ level finite element models by incorporating information regarding tissue structure and composition from advanced imaging techniques. This approach could thereby provide a preclinical tool to predict bone mechanics following prosthetic implantation or bone fracture during disease. PMID:22659366

  18. Space flight and bone formation

    NASA Technical Reports Server (NTRS)

    Doty, St B.

    2004-01-01

    Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

  19. Hedgehog signaling mediates woven bone formation and vascularization during stress fracture healing.

    PubMed

    Kazmers, Nikolas H; McKenzie, Jennifer A; Shen, Tony S; Long, Fanxin; Silva, Matthew J

    2015-12-01

    Hedgehog (Hh) signaling is critical in developmental osteogenesis, and recent studies suggest it may also play a role in regulating osteogenic gene expression in the post-natal setting. However, there is a void of studies directly assessing the effect of Hh inhibition on post-natal osteogenesis. This study utilized a cyclic loading-induced ulnar stress fracture model to evaluate the hypothesis that Hh signaling contributes to osteogenesis and angiogenesis during stress fracture healing. Immediately prior to loading, adult rats were given GDC-0449 (Vismodegib - a selective Hh pathway inhibitor; 50mg/kg orally twice daily), or vehicle. Hh signaling was upregulated in response to stress fracture at 3days (Ptch1, Gli1 expression), and was markedly inhibited by GDC-0449 at 1day and 3days in the loaded and non-loaded ulnae. GDC-0449 did not affect Hh ligand expression (Shh, Ihh, Dhh) at 1day, but decreased Shh expression by 37% at 3days. GDC-0449 decreased woven bone volume (-37%) and mineral density (-17%) at 7days. Dynamic histomorphometry revealed that the 7day callus was composed predominantly of woven bone in both groups. The observed reduction in woven bone occurred concomitantly with decreased expression of Alpl and Ibsp, but was not associated with differences in early cellular proliferation (as determined by callus PCNA staining at 3days), osteoblastic differentiation (Osx expression at 1day and 3days), chondrogenic gene expression (Acan, Sox9, and Col2?1 expression at 1day and 3days), or bone resorption metrics (callus TRAP staining at 3days, Rankl and Opg expression at 1day and 3days). To evaluate angiogenesis, vWF immunohistochemistry showed that GDC-0449 reduced fracture callus blood vessel density by 55% at 3days, which was associated with increased Hif1? gene expression (+30%). Dynamic histomorphometric analysis demonstrated that GDC-0449 also inhibited lamellar bone formation. Lamellar bone analysis of the loaded limb (directly adjacent to the woven bone callus) showed that GDC-0449 significantly decreased mineral apposition rate (MAR) and bone formation rate (BFR/BS) (-17% and -20%, respectively). Lamellar BFR/BS in the non-loaded ulna was also significantly decreased (-37%), indicating that Hh signaling was required for normal bone modeling. In conclusion, Hh signaling plays an important role in post-natal osteogenesis in the setting of stress fracture healing, mediating its effects directly through regulation of bone formation and angiogenesis. PMID:26348666

  20. Clay enriched silk biomaterials for bone formation.

    PubMed

    Mieszawska, Aneta J; Llamas, Jabier Gallego; Vaiana, Christopher A; Kadakia, Madhavi P; Naik, Rajesh R; Kaplan, David L

    2011-08-01

    The formation of silk protein/clay composite biomaterials for bone tissue formation is described. Silk fibroin serves as an organic scaffolding material offering mechanical stability suitable for bone-specific uses. Clay montmorillonite (Cloisite® Na(+)) and sodium silicate are sources of osteoinductive silica-rich inorganic species, analogous to bioactive bioglass-like bone repair biomaterial systems. Different clay particle-silk composite biomaterial films were compared with silk films doped with sodium silicate as controls for the support of human bone marrow derived mesenchymal stem cells in osteogenic culture. The cells adhered to and proliferated on the silk/clay composites over 2 weeks. Quantitative real time polymerase chain reaction analysis revealed increased transcript levels for alkaline phosphatase, bone sialoprotein, and collagen type 1 osteogenic markers in the cells cultured on the silk/clay films in comparison with the controls. Early evidence of bone formation based on collagen deposition at the cell-biomaterial interface was also found, with more collagen observed for the silk films with higher contents of clay particles. The data suggest that silk/clay composite systems may be useful for further study for bone regenerative needs. PMID:21549864

  1. Extensive bone formation in a painful blind eye.

    PubMed

    Ekinci Koktekir, Bengu; Karabagli, Pinar; Gonul, Saban; Bozkurt, Banu; Gedik, Sansal

    2014-11-01

    Osseous metaplasia may occur in phthisis bulbi, usually caused by long-standing retinal detachment, ocular trauma, or inflammation. However, extensive intraocular bone formation is a rare phenomenon. We report a case with long-standing phthisis bulbi demonstrating subretinal extensive bone formation. Results of histopathologic examination revealed extensive bone formation overlying the choroid with accompanying bone marrow without hematopoiesis. PMID:25364973

  2. Direct bone formation on alumina bead composite.

    PubMed

    Kobayashi, M; Kikutani, T; Kokubo, T; Nakamura, T

    1997-12-15

    We have developed a composite (designated ABC), consisting of alumina bead powder as an inorganic filler and bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin as an organic matrix, which allows direct bone formation on its surface in vivo. Alumina bead powder was manufactured by fusing crushed alpha-alumina powder and quenching it. The beads took spherical form 3 microns in average size. According to powder X-ray diffraction and Fourier transform infrared spectroscopy, the alumina bead powder was composed of amorphous and delta-crystal phases of alumina in its main crystal structure. Fused-quenched silica glass-filled composite (SGC) was used as a control. The proportion of filler added to the composites was 70% w/w. Mechanical testing of the ABC indicated that it would be strong enough for use under weight-bearing conditions. No apatite formation was detected on the surfaces of either composite after soaking in simulated body fluid for 28 days in vitro. Histological examination of rat tibiae for up to 8 weeks revealed that ABC bonded to bone directly via a layer of calcium, phosphorus, and alumina with no interposed soft-tissue layer. Moreover, the amount of bone directly apposed to the ABC surface increased with time, whereas with SGC there was poor direct bone formation even at 8 weeks. The precise mechanism of direct bone formation on ABC is as yet unknown but it is possible that changes in the crystallinity of alumina, which is known to be highly biocompatible, contribute to its excellent osteoconductivity in vivo. Although bioactive materials such as Bioglass or apatite and wollastonite-containing glass-ceramic have previously been reported to form bone-like apatite on their surfaces under acellular conditions via simple chemical reactions, ABC does not have such characteristics, and presenting favorable conditions for osteoconduction and tissue calcification may lead to direct bone formation on its surface in vivo. PMID:9407305

  3. [BMP signaling and bone formation].

    PubMed

    Katagiri, Takenobu

    2012-11-01

    Bone morphogenetic proteins (BMPs) bind to two types of membrane receptors. Type II receptor phosphorylates type I receptor, then the phosphorylated type I receptor phosphorylates downstream effectors, such as Smads. Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic ossification in skeletal muscle tissue. ALK2, a BMP type I receptor has been mutated in patients with FOP. The mutant ALK2 phosphorylates Smads in the absence of BMPs. In FOP, muscle injury may enhance BMP signaling via Smads to induce acute heterotopic ossification. Inhibitors of the BMP-Smad pathway will be useful to develop novel treatments for FOP. PMID:23103811

  4. Rescuing Loading Induced Bone Formation at Senescence

    PubMed Central

    Srinivasan, Sundar; Ausk, Brandon J.; Prasad, Jitendra; Threet, Dewayne; Bain, Steven D.; Richardson, Thomas S.; Gross, Ted S.

    2010-01-01

    The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential. PMID:20838577

  5. In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone

    NASA Astrophysics Data System (ADS)

    Schwiedrzik, Jakob; Raghavan, Rejin; Bürki, Alexander; Lenader, Victor; Wolfram, Uwe; Michler, Johann; Zysset, Philippe

    2014-07-01

    Ageing societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the hierarchical organization of bone. Here, we investigate the mechanical response under monotonic and cyclic compression of both single osteonal lamellae and macroscopic samples containing numerous osteons. Micropillar compression tests in a scanning electron microscope, microindentation and macroscopic compression tests were performed on dry ovine bone to identify the elastic modulus, yield stress, plastic deformation, damage accumulation and failure mechanisms. We found that isolated lamellae exhibit a plastic behaviour, with higher yield stress and ductility but no damage. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behaviour of bone at the microscale to a quasi-brittle response driven by the growth of cracks along interfaces or in the vicinity of pores at the macroscale.

  6. In situ micropillar compression reveals superior strength and ductility but an absence of damage in lamellar bone.

    PubMed

    Schwiedrzik, Jakob; Raghavan, Rejin; Bürki, Alexander; LeNader, Victor; Wolfram, Uwe; Michler, Johann; Zysset, Philippe

    2014-07-01

    Ageing societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the hierarchical organization of bone. Here, we investigate the mechanical response under monotonic and cyclic compression of both single osteonal lamellae and macroscopic samples containing numerous osteons. Micropillar compression tests in a scanning electron microscope, microindentation and macroscopic compression tests were performed on dry ovine bone to identify the elastic modulus, yield stress, plastic deformation, damage accumulation and failure mechanisms. We found that isolated lamellae exhibit a plastic behaviour, with higher yield stress and ductility but no damage. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behaviour of bone at the microscale to a quasi-brittle response driven by the growth of cracks along interfaces or in the vicinity of pores at the macroscale. PMID:24907926

  7. Tubular growth and bead formation in the lyotropic lamellar phase of a lipid.

    PubMed

    Bhatia, Tripta; Hatwalne, Yashodhan; Madhusudana, N V

    2015-07-28

    We use fluorescence confocal polarised microscopy (FCPM) to study tubular growth upon hydration of dry DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) in water and water-glycerol mixtures. We have developed a model to relate the FCPM intensity profiles to the multilamellar structures of the tubules. Insertion of an additional patch inside a tubule produces a beaded structure, while a straight configuration is retained if the growth is on the outside. We use a simple model to suggest that reduction in overall curvature energy drives bead formation. PMID:26066670

  8. Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength of Intact Bones in Adult Male Rats

    PubMed Central

    Suen, Pui Kit; Zhu, Tracy Y.; Chow, Dick Ho Kiu; Huang, Le; Zheng, Li-Zhen; Qin, Ling

    2015-01-01

    We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25?mg/kg, 2 times per week) treatment for 9 weeks. Compared with vehicle control, Scl-Ab treatment significantly improved trabecular and cortical bone mass and microarchitecture at L5 vertebrae and left femora by micro-CT at week 6 and 9. Mechanical testing showed that Scl-Ab treatment resulted in significantly higher stiffness, energy to failure and ultimate load at the femora at week 9. Mineral apposition rate, mineralizing surface and bone formation rate on the trabecular bone in the distal femora was significantly increased in Scl-Ab group at week 6 and 9. The administered Scl-Ab was localized in the osteocytes and beta-catenin was strongly expressed in osteoblasts. Scl-Ab treatment significantly increased serum P1NP level and there was no between-group difference in serum level of CTX-1. In conclusion, Scl-Ab treatment could induce rapid and sustained increase in bone formation, bone mass and bone strength in non-operated bones. Sclerostin inhibition might be advantageous to prevent secondary fracture(s). PMID:26494536

  9. Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength of Intact Bones in Adult Male Rats.

    PubMed

    Suen, Pui Kit; Zhu, Tracy Y; Chow, Dick Ho Kiu; Huang, Le; Zheng, Li-Zhen; Qin, Ling

    2015-01-01

    We investigated the systemic effect of sclerostin monoclonal antibody (Scl-Ab) treatment on intact non-operated bones in an open osteotomy male Sprague Dawley (SD) rat model. Six-month-old male SD rats were subjected to transverse osteotomy at the right femur mid-shaft. Rats were injected subcutaneously with vehicle or Scl-Ab (25?mg/kg, 2 times per week) treatment for 9 weeks. Compared with vehicle control, Scl-Ab treatment significantly improved trabecular and cortical bone mass and microarchitecture at L5 vertebrae and left femora by micro-CT at week 6 and 9. Mechanical testing showed that Scl-Ab treatment resulted in significantly higher stiffness, energy to failure and ultimate load at the femora at week 9. Mineral apposition rate, mineralizing surface and bone formation rate on the trabecular bone in the distal femora was significantly increased in Scl-Ab group at week 6 and 9. The administered Scl-Ab was localized in the osteocytes and beta-catenin was strongly expressed in osteoblasts. Scl-Ab treatment significantly increased serum P1NP level and there was no between-group difference in serum level of CTX-1. In conclusion, Scl-Ab treatment could induce rapid and sustained increase in bone formation, bone mass and bone strength in non-operated bones. Sclerostin inhibition might be advantageous to prevent secondary fracture(s). PMID:26494536

  10. Induction of heterotopic bone marrow formation in osteopetrotic rats by allogeneic decalcified bone matrix.

    PubMed

    Dziedzic-Goc?awska, A; Ostrowski, K; Moutier, R; Toyama, K; Lamendin, H

    1978-01-01

    Contrary to theoretical expectations in osteopetrotic mutants heterotopic bone marrow formation was closely associated with osteogenesis, what is not observed in the orthotopic skeletal bones in these animals. PMID:749757

  11. Effect of spaceflight on periosteal bone formation in rats

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey, E. R.

    1983-01-01

    Male Wistar rats were placed in orbit for 18.5 days aboard the Soviet COSMOS 1129 biological satellite. Tetracycline was administered before and after spaceflight to label areas of bone formation. An inhibition of periosteal bone formation occurred during spaceflight in the tibial and humeral diaphyses, but this defect was corrected during the postflight period. The increased extent of arrest lines at these skeletal sites suggested that periosteal bone formation may have even ceased during spaceflight. The rib exhibited a small but nonsignificant decrease in periosteal bone formation. Endosteal bone resorption was not affected markedly by spaceflight conditions. The observed inhibition of periosteal bone formation may be a result of mechanical unloading, but endocrine factors cannot be ruled out.

  12. PINP: a serum biomarker of bone formation in the rat.

    PubMed

    Hale, L V; Galvin, R J Sells; Risteli, J; Ma, Y L; Harvey, A K; Yang, X; Cain, R L; Zeng, Q; Frolik, C A; Sato, M; Schmidt, A L; Geiser, A G

    2007-04-01

    Serum PINP has emerged as a reliable marker of bone turnover in humans and is routinely used to monitor bone formation. However, the effects of PTH (1-34) on bone turnover have not been evaluated following short-term treatment. We present data demonstrating that PINP is an early serum biomarker in the rat for assessing bone anabolic activity in response to treatment with PTH (1-38). Rat serum PINP levels were found to increase following as few as 6 days of treatment with PTH (1-38) and these increases paralleled expression of genes associated with bone formation, as well as, later increases in BMD. Additionally, PINP levels were unaffected by treatment with an antiresorptive bisphosphonate. PINP may be used to detect PTH-induced early bone formation in the rat and may be more generally applicable for preclinical testing of potential bone anabolic drugs. PMID:17258520

  13. Inhibition of cortical and trabecular bone formation in the long bones of immobilized monkeys

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey, E. R.

    1983-01-01

    Tetracycline derivatives are administered on three separate occasions to label the sites of bone formation. Determinations are made of the tetracycline-labeling frequency and mineral apposition rate of osteons and trabecular bone surfaces in the humerus and femur. The inhibition of bone formation induced by immobilization is found to be more pronounced in trabecular bone. The immobilized monkeys exhibit a moderate, but statistically nonsignificant, reduction in the percentage of osteons forming bone. Conversely, the dramatic decline in the percentage of trabecular surfaces undergoing bone formation in the monkeys is found to be highly significant. The diminished rate of mineral apposition in osteons is seen as suggesting that osteoblastic activity is impaired in cortical bone during immobilization.

  14. The impact of skeletal unloading on bone formation

    NASA Technical Reports Server (NTRS)

    Bikle, Daniel D.; Sakata, Takeshi; Halloran, Bernard P.

    2003-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During space flight bone is lost principally from the bones most loaded in the 1 g environment. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. It seems likely that matrix/cell interactions will underlie much of the mechanocoupling. Integrins are a prime mediator of such interactions. The role for systemic hormones such as PTH, GH and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs and TGF beta in modulating the cellular response to load remains unclear. Our studies demonstrate that skeletal unloading leads to resistance to the anabolic actions of IGF-I on bone as a result of failure of IGF-I to activate its own signaling pathways. This is associated with a reduction in integrin expression, suggesting crosstalk between these two pathways. As the mechanism(s) by which bone responds to changes in mechanical load with changes in bone formation is further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, and that such understanding will lead to effective treatment for disuse osteoporosis in addition to preventive measures for the bone loss that accompanies space travel.

  15. A Novel Chitosan-?PGA Polyelectrolyte Complex Hydrogel Promotes Early New Bone Formation in the Alveolar Socket Following Tooth Extraction

    PubMed Central

    Chang, Hao-Hueng; Wang, Yin-Lin; Chiang, Yu-Chih; Chen, Yen-Liang; Chuang, Yu-Horng; Tsai, Shang-Jye; Heish, Kuo-Huang; Lin, Feng-Huei; Lin, Chun-Pin

    2014-01-01

    A novel chitosan-?PGA polyelectrolyte complex hydrogel (C-PGA) has been developed and proven to be an effective dressing for wound healing. The purpose of this study was to evaluate if C-PGA could promote new bone formation in the alveolar socket following tooth extraction. An animal model was proposed using radiography and histomorphology simultaneously to analyze the symmetrical sections of Wistar rats. The upper incisors of Wistar rats were extracted and the extraction sockets were randomly treated with gelatin sponge, neat chitosan, C-PGA, or received no treatment. The extraction sockets of selected rats from each group were evaluated at 1, 2, 4, or 6 wk post-extraction. The results of radiography and histopathology indicated that the extraction sockets treated with C-PGA exhibited lamellar bone formation (6.5%) as early as 2 wk after the extraction was performed. Moreover, the degree of new bone formation was significantly higher (P < 0.05) in the extraction sockets treated with C-PGA at 6 wk post-extraction than that in the other study groups. In this study, we demonstrated that the proposed animal model involving symmetrical sections and simultaneous radiography and histomorphology evaluation is feasible. We also conclude that the novel C-PGA has great potential for new bone formation in the alveolar socket following tooth extraction. PMID:24658174

  16. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    SciTech Connect

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-08-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered)) . Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research Highlights: > 3-Day imatinib treatment. > Causes growth plate anomalies in young rats. > Causes biomechanical changes and significant bone loss at distal trabecular bone. > Results in loss of osteoclasts at osteochondral junction.

  17. Brief Review of Models of Ectopic Bone Formation

    PubMed Central

    Scott, Michelle A.; Levi, Benjamin; Askarinam, Asal; Nguyen, Alan; Rackohn, Todd; Ting, Kang; Soo, Chia

    2012-01-01

    Ectopic bone formation is a unique biologic entity—distinct from other areas of skeletal biology. Animal research models of ectopic bone formation most often employ rodent models and have unique advantages over orthotopic (bone) environments, including a relative lack of bone cytokine stimulation and cell-to-cell interaction with endogenous (host) bone-forming cells. This allows for relatively controlled in vivo experimental bone formation. A wide variety of ectopic locations have been used for experimentation, including subcutaneous, intramuscular, and kidney capsule transplantation. The method, benefits and detractions of each method are summarized in the following review. Briefly, subcutaneous implantation is the simplest method. However, the most pertinent concern is the relative paucity of bone formation in comparison to other models. Intramuscular implantation is also widely used and relatively simple, however intramuscular implants are exposed to skeletal muscle satellite progenitor cells. Thus, distinguishing host from donor osteogenesis becomes challenging without cell-tracking studies. The kidney capsule (perirenal or renal capsule) method is less widely used and more technically challenging. It allows for supraphysiologic blood and nutrient resource, promoting robust bone growth. In summary, ectopic bone models are extremely useful in the evaluation of bone-forming stem cells, new osteoinductive biomaterials, and growth factors; an appropriate choice of model, however, will greatly increase experimental success. PMID:22085228

  18. Leptin regulates bone formation via the sympathetic nervous system

    NASA Technical Reports Server (NTRS)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  19. Vascular biology and bone formation: hints from HIF

    PubMed Central

    Towler, Dwight A.

    2007-01-01

    In this issue of the JCI, Wang, Clemens, and colleagues demonstrate that hypoxia-inducible factor ? (HIF?) signaling in bone-building osteoblasts is central to the coupling of angiogenesis and long bone development in mice (see the related article beginning on page 1616). They show that bone formation controlled by osteoblast HIF? signaling is not cell autonomous but is coupled to skeletal angiogenesis dependent upon VEGF signaling. Thus, strategies that promote HIF? signaling in osteoblasts may augment bone formation and accelerate fracture repair. PMID:17549250

  20. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Engelholm, Lars H; Delaissé, Jean-Marie

    2014-01-10

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is the physical site where coupling of bone resorption to bone formation occurs. PMID:24333871

  1. Osteopenia and decreased bone formation in osteonectin-deficient mice.

    PubMed

    Delany, A M; Amling, M; Priemel, M; Howe, C; Baron, R; Canalis, E

    2000-04-01

    Bone continuously remodels in response to mechanical and physiological stresses, allowing vertebrates to renew bone as adults. Bone remodeling consists of the cycled synthesis and resorption of collagenous and noncollagenous extracellular matrix proteins, and an imbalance in this process can lead to disease states such as osteoporosis, or more rarely, osteopetrosis. There is evidence that the extracellular matrix glycoprotein osteonectin or secreted protein acidic and rich in cysteine (BM-40) may be important in bone remodeling. Osteonectin is abundant in bone and is expressed in areas of active remodeling outside the skeleton. In vitro studies indicate that osteonectin can bind collagen and regulate angiogenesis, metalloproteinase expression, cell proliferation, and cell-matrix interactions. In some osteopenic states, such as osteogenesis imperfecta and selected animal models for bone fragility, osteonectin expression is decreased. To determine the function of osteonectin in bone, we used contact x-ray, histomorphometry, and Northern blot analysis to characterize the skeletal phenotype of osteonectin-null mice. We found that osteonectin-null mice have decreased bone formation and decreased osteoblast and osteoclast surface and number, leading to decreased bone remodeling with a negative bone balance and causing profound osteopenia. These data indicate that osteonectin supports bone remodeling and the maintenance of bone mass in vertebrates. PMID:10749571

  2. Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

    NASA Technical Reports Server (NTRS)

    Cann, Christopher; Young, Donald R.

    1976-01-01

    Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

  3. Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.

    PubMed

    Stein, Koen; Prondvai, Edina

    2014-02-01

    We present novel findings on sauropod bone histology that cast doubt on general palaeohistological concepts concerning the true nature of woven bone in primary cortical bone and its role in the rapid growth and giant body sizes of sauropod dinosaurs. By preparing and investigating longitudinal thin sections of sauropod long bones, of which transverse thin sections were published previously, we found that the amount of woven bone in the primary complex has been largely overestimated. Using comparative cellular and light-extinction characteristics in the two section planes, we revealed that the majority of the bony lamina consists of longitudinally organized primary bone, whereas woven bone is usually represented only by a layer a few cells thin in the laminae. Previous arguments on sauropod biology, which have been based on the overestimated amount, misinterpreted formation process and misjudged role of woven bone in the plexiform bone formation of sauropod dinosaurs, are thereby rejected. To explain the observed pattern in fossil bones, we review the most recent advances in bone biology concerning bone formation processes at the cellular and tissue levels. Differentiation between static and dynamic osteogenesis (SO and DO) and the revealed characteristics of SO- versus DO-derived bone tissues shed light on several questions raised by our palaeohistological results and permit identification of these bone tissues in fossils with high confidence. By presenting the methods generally used for investigating fossil bones, we show that the major cause of overestimation of the amount of woven bone in previous palaeohistological studies is the almost exclusive usage of transverse sections. In these sections, cells and crystallites of the longitudinally organized primary bone are cut transversely, thus cells appear rounded and crystallites remain dark under crossed plane polarizers, thereby giving the false impression of woven bone. In order to avoid further confusion in palaeohistological studies, we introduce new osteohistological terms as well as revise widely used but incorrect terminology. To infer the role of woven bone in the bone formation of fast-growing tetrapods, we review some aspects of the interrelationships between the vascularity of bone tissues, basal metabolic rate, body size and growth rate. By putting our findings into the context of osteogenesis, we provide a new model for the diametrical limb bone growth of sauropods and present new implications for the evolution of fast growth in vertebrates. Since biomechanical studies of bone tissues suggest that predominant collagen fibre orientation (CFO) is controlled by endogenous, functional and perhaps phylogenetic factors, the relationship between CFO and bone growth rate as defined by Amprino's rule, which has been the basis for the biological interpretation of several osteohistological features, must be revised. Our findings draw attention to the urgent need for revising widely accepted basic concepts of palaeohistological studies, and for a more integrative approach to bone formation, biomechanics and bone microstructural features of extant and extinct vertebrates to infer life history traits of long extinct, iconic animals like dinosaurs. PMID:23647662

  4. Burn Injury Enhances Bone Formation in Heterotopic Ossification Model

    PubMed Central

    Peterson, Jonathan R.; De La Rosa, Sara; Sun, Hongli; Eboda, Oluwatobi; Cilwa, Katherine E.; Donneys, Alexis; Morris, Michael; Buchman, Steven R.; Cederna, Paul S.; Krebsbach, Paul H.; Wang, Stewart C.; Levi, Benjamin

    2015-01-01

    Objective To demonstrate the pro-osteogenic effect of burn injury on heterotopic bone formation using a novel burn ossicle in vivo model. Background Heterotopic ossification (HO), or the abnormal formation of bone in soft tissue, is a troubling sequela of burn and trauma injuries. The exact mechanism by which burn injury influences bone formation is unknown. The aim of this study was to develop a mouse model to study the effect of burn injury on heterotopic bone formation. We hypothesized that burn injury would enhance early vascularization and subsequent bone formation of subcutaneously implanted mesenchymal stem cells. Methods Mouse adipose-derived stem cells were harvested from C57/BL6 mice, transfected with a BMP-2 adenovirus, seeded on collagen scaffolds (ossicles), and implanted subcutaneously in the flank region of 8 adult mice. Burn and sham groups were created with exposure of 30% surface area on the dorsum to 60°C water or 30°C water for 18 seconds, respectively (n = 4/group). Heterotopic bone volume was analyzed in vivo by micro-computed tomography for 3 months. Histological analysis of vasculogenesis was performed with platelet endothelial cell adhesion molecule staining. Osteogenic histological analysis was performed by Safranin O, Picrosirius red, and aniline blue staining. Qualitative analysis of heterotopic bone composition was completed with ex vivo Raman spectroscopy. Results Subcutaneously implanted ossicles formed heterotopic bone. Ossicles from mice with burn injuries developed significantly more bone than sham control mice, analyzed by micro-computed tomography at 1, 2, and 3 months (P < 0.05), and had enhanced early and late endochondral ossification as demonstrated by Safranin O, Picrosirius red, and aniline blue staining. In addition, burn injury enhanced vascularization of the ossicles (P < 0.05). All ossicles demonstrated chemical composition characteristic of bone as demonstrated by Raman spectroscopy. Conclusions Burn injury increases the predilection to osteogenic differentiation of ectopically implanted ossicles. Early differences in vascularity correlated with later bone development. Understanding the role of burn injury on heterotopic bone formation is an important first step toward the development of treatment strategies aimed to prevent unwanted and detrimental heterotopic bone formation. PMID:23673767

  5. Overexpressing Sonic Hedgehog Peptide Restores Periosteal Bone Formation in a Murine Bone Allograft Transplantation Model

    PubMed Central

    Huang, Chunlan; Tang, Minghui; Yehling, Eric; Zhang, Xinping

    2014-01-01

    Although activation of hedgehog (Hh) signaling has been shown to induce osteogenic differentiation in vitro and bone formation in vivo, the underlying mechanisms and the potential use of Hh-activated mesenchymal progenitors in bone defect repair remain elusive. In this study, we demonstrated that implantation of periosteal-derived mesenchymal progenitor cells (PDMPCs) that overexpressed an N-terminal sonic hedgehog peptide (ShhN) via an adenoviral vector (Ad-ShhN) restored periosteal bone collar formation in a 4-mm segmental bone allograft model in immunodeficient mice. Ad-ShhN enhanced donor cell survival and microvessel formation in collagen scaffold at 2 weeks after surgery and induced donor cell–dependent bone formation at 6 weeks after surgery. Fluorescence-activated cell sorting analysis further showed that Ad-ShhN-PDMPC–seeded scaffold contained a twofold more CD45?Sca-1+CD34+VEGFR2+ endothelial progenitors than Ad-LacZ-PDMPC–seeded scaffold at day 7 after surgery. Ad-ShhN–transduced PDMPCs induced a 1.8-fold more CD31+ microvessel formation than Ad-LacZ–transduced PDMPCs in a coculture of endothelial progenitors and PDMPCs. Taken together, our data show that overexpression of ShhN in mesenchymal progenitors improves bone defect reconstruction by enhancing donor progenitor cell survival, differentiation, and scaffold revascularization at the site of compromised periosteum. Hh agonist–based therapy, therefore, merits further investigation in tissue engineering–based applications aimed at enhancing bone defect repair and reconstruction. PMID:24089140

  6. Biomimetism, biomimetic matrices and the induction of bone formation

    PubMed Central

    Ripamonti, Ugo

    2009-01-01

    Bone formation by induction initiates by invocation of osteogenic soluble molecular signals of the transforming growth factor-? (TGF-?) superfamily; when combined with insoluble signals or substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell differentiation into osteoblastic cell lines secreting bone matrix at site of surgical implantation. A most exciting and novel strategy to initiate bone formation by induction is to carve smart self-inducing geometric concavities assembled within biomimetic constructs. The assembly of a series of repetitive concavities within the biomimetic constructs is endowed with the striking prerogative of differentiating osteoblast-like cells attached to the biomimetic matrices initiating the induction of bone formation as a secondary response. Importantly, the induction of bone formation is initiated without the exogenous application of the osteogenic soluble molecular signals of the TGF-? superfamily. This manuscript reviews the available data on this fascinating phenomenon, i.e. biomimetic matrices that arouse and set into motion the mammalian natural ability to heal thus constructing biomimetic matrices that in their own right set into motion inductive regenerative phenomena initiating the cascade of bone differentiation by induction biomimetizing the remodelling cycle of the primate cortico-cancellous bone. PMID:19175690

  7. Biomimetic matrices self-initiating the induction of bone formation.

    PubMed

    Ripamonti, Ugo; Roden, Laura C; Ferretti, Carlo; Klar, Roland M

    2011-09-01

    The new strategy of tissue engineering, and regenerative medicine at large, is to construct biomimetic matrices to mimic nature's hierarchical structural assemblages and mechanisms of simplicity and elegance that are conserved throughout genera and species. There is a direct spatial and temporal relationship of morphologic and molecular events that emphasize the biomimetism of the remodeling cycles of the osteonic corticocancellous bone versus the "geometric induction of bone formation," that is, the induction of bone by "smart" concavities assembled in biomimetic matrices of macroporous calcium phosphate-based constructs. The basic multicellular unit of the corticocancellous bone excavates a trench across the bone surface, leaving in its wake a hemiosteon rather than an osteon, that is, a trench with cross-sectional geometric cues of concavities after cyclic episodes of osteoclastogenesis, eventually leading to osteogenesis. The concavities per se are geometric regulators of growth-inducing angiogenesis and osteogenesis as in the remodeling processes of the corticocancellous bone. The concavities act as a powerful geometric attractant for myoblastic/myoendothelial and/or endothelial/pericytic stem cells, which differentiate into bone-forming cells. The lacunae, pits, and concavities cut by osteoclastogenesis within the biomimetic matrices are the driving morphogenetic cues that induce bone formation in a continuum of sequential phases of resorption/dissolution and formation. To induce the cascade of bone differentiation, the soluble osteogenic molecular signals of the transforming growth factor ? supergene family must be reconstituted with an insoluble signal or substratum that triggers the bone differentiation cascade. By carving a series of repetitive concavities into solid and/or macroporous biomimetic matrices of highly crystalline hydroxyapatite or biphasic hydroxyapatite/?-tricalcium phosphate, we were able to embed smart biologic functions within intelligent scaffolds for tissue engineering of bone. The concavities assembled in the bioceramic constructs biomimetize the remodeling cycle of the corticocancellous bone and are endowed with multifunctional pleiotropic self-assembly capacities, initiating angiogenesis and bone formation by induction without the exogenous applications of the osteogenic-soluble molecular signals of the transforming growth factor ? supergene family. The incorporation of specific biologic activities into biomimetic matrices by manipulating the geometry of the substratum, defined as geometric induction of bone formation, is now helping to engineer therapeutic osteogenesis in clinical contexts. PMID:21959451

  8. Functional Diversity of Fibroblast Growth Factors in Bone Formation

    PubMed Central

    Minamizaki, Tomoko; Yoshiko, Yuji

    2015-01-01

    The functional significance of fibroblast growth factor (FGF) signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs). Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects. PMID:25873956

  9. Lamellar stack formation and degradative behaviors of hydrolytically degraded poly(?-caprolactone) and poly(glycolide-?-caprolactone) blended fibers.

    PubMed

    Chung, Amy S; Hwang, Ho Seong; Das, Debobrato; Zuk, Patricia; McAllister, David R; Wu, Benjamin M

    2012-01-01

    Electrospun fibrous mats have gained popularity in bioengineering over the past decade, but few papers detail their degradative mechanisms. To address this, blends of hydrophobic poly(?-caprolactone) (PCL) and hydrophilic PGA-PCL-PGA triblock copolymer were electrospun into aligned fibrous mats to assess the copolymers' mechanical and degradative properties. Increased hydrophilic triblock content led to enhanced morphological uniformity of fiber, tightening of fiber diameters, increased storage and Young's modulus, and decreased elongation. The corresponding decrease in hydrophobic PCL content led to faster hydrolytic degradation rate, as reflected by enhanced decrease in mass, molecular weight, and modulus loss at 25, 37, and 45°C. The activation energy for hydrolytic degradation for 15:85 PCL: triblock copolymer was approximately half that of 85:15 PCL: triblock copolymer. Detailed examination of fiber morphology and crystallinity revealed initial surface erosion followed by the evolution of crystalline lamellar stacks and bulk degradation at 37°C. Because of the high surface to volume and short diffusion length scale of the small diameter fibers, surface and bulk degradation may both contribute to the hydrolytic degradative behavior of these electrospun fibrous mats. Electrospun mats' distinct architecture that embodies high specific surface to volume and interfiber porous ultrastructures that lead to their unique degradative behaviors hold much potential for significant impact in the field of tissue engineering and controlled drug delivery. PMID:22069303

  10. Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone

    PubMed Central

    Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

    2011-01-01

    Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

  11. FGF/FGFR signaling in bone formation: progress and perspectives.

    PubMed

    Marie, Pierre J; Miraoui, Hichem; Sévère, Nicolas

    2012-04-01

    Fibroblast growth factors (FGFs) are important molecules that control bone formation. FGF act by activating FGF receptors (FGFRs) and downstream signaling pathways that control cells of the osteoblast lineage. Recent advances have been made in the identification of FGF/FGFR signaling pathways that control osteogenesis. Indeed, studies of mouse and human models provided novel insights into the signaling pathways that control bone formation. Genomic studies also highlighted the implication of molecular targets of FGF/FGFR signaling regulating osteoblastogenesis. Recent studies further revealed the important role of crosstalks between FGF/FGFR signaling and other signaling pathways in the regulation of osteogenesis. Finally, the importance of the mechanisms modulating FGFR degradation in the control of osteoblast differentiation has been recently revealed. This short review summarizes the recently described mechanisms underlying FGF/FGFR signaling that are involved in the control of osteoblastogenesis. This knowledge may have potential therapeutic implications in skeletal disorders characterized by abnormal bone formation. PMID:22292523

  12. Non-Linear Pattern Formation in Bone Growth and Architecture

    PubMed Central

    Salmon, Phil

    2014-01-01

    The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here – chaotic non-linear pattern formation (NPF) – which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of “group intelligence” exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called “particle swarm optimization” (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating “socially” in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or “feedback” between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent consequence of the latter. PMID:25653638

  13. Non-linear pattern formation in bone growth and architecture.

    PubMed

    Salmon, Phil

    2014-01-01

    The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here - chaotic non-linear pattern formation (NPF) - which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of "group intelligence" exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called "particle swarm optimization" (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating "socially" in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or "feedback" between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent consequence of the latter. PMID:25653638

  14. DYSAPOPTOSIS OF OSTEOBLASTS AND OSTEOCYTES INCREASES CANCELLOUS BONE FORMATION BUT EXAGGERATES BONE POROSITY WITH AGE

    PubMed Central

    Jilka, Robert L.; O’Brien, Charles A.; Roberson, Paula K.; Bonewald, Lynda F.; Weinstein, Robert S.; Manolagas, Stavros C.

    2013-01-01

    Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in non-vertebral fractures after age 65 in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-?B ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age. PMID:23761243

  15. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation

    PubMed Central

    Kim, Ji-Beom; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-01-01

    Background Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. Methods The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. Results The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. Conclusions DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest that percutaneous DBM administration at the end of the distraction period or in the early consolidation period may stimulate regenerate bone formation and consolidation in a clinical situation with delayed bone healing during DO. PMID:26330963

  16. Thyrostimulin Regulates Osteoblastic Bone Formation During Early Skeletal Development

    PubMed Central

    van der Spek, Anne; Logan, John G.; Gogakos, Apostolos; Bagchi-Chakraborty, Jayashree; Murphy, Elaine; van Zeijl, Clementine; Down, Jenny; Croucher, Peter I.; Boyde, Alan; Boelen, Anita

    2015-01-01

    The ancestral glycoprotein hormone thyrostimulin is a heterodimer of unique glycoprotein hormone subunit alpha (GPA)2 and glycoprotein hormone subunit beta (GPB)5 subunits with high affinity for the TSH receptor. Transgenic overexpression of GPB5 in mice results in cranial abnormalities, but the role of thyrostimulin in bone remains unknown. We hypothesized that thyrostimulin exerts paracrine actions in bone and determined: 1) GPA2 and GPB5 expression in osteoblasts and osteoclasts, 2) the skeletal consequences of thyrostimulin deficiency in GPB5 knockout (KO) mice, and 3) osteoblast and osteoclast responses to thyrostimulin treatment. Gpa2 and Gpb5 expression was identified in the newborn skeleton but declined rapidly thereafter. GPA2 and GPB5 mRNAs were also expressed in primary osteoblasts and osteoclasts at varying concentrations. Juvenile thyrostimulin-deficient mice had increased bone volume and mineralization as a result of increased osteoblastic bone formation. However, thyrostimulin failed to induce a canonical cAMP response or activate the noncanonical Akt, ERK, or mitogen-activated protein kinase (P38) signaling pathways in primary calvarial or bone marrow stromal cell-derived osteoblasts. Furthermore, thyrostimulin did not directly inhibit osteoblast proliferation, differentiation or mineralization in vitro. These studies identify thyrostimulin as a negative but indirect regulator of osteoblastic bone formation during skeletal development. PMID:26018249

  17. Modeling mechanochromatic lamellar gels

    NASA Astrophysics Data System (ADS)

    Hong, Wei; Wang, Xiao

    2012-03-01

    Consisting of alternating swelling and nonswelling polymeric layers (SLs and NLs), lamellar gels are one-dimensional photonic crystals with mechanically tunable optical properties. The lamellar structure induces a constraint between the SLs and the NLs, resulting in a highly anisotropic swelling behavior that is coupled with deformation. The coupling gives rise to the mechanochromatic effect, i.e., the color change in the material in response to mechanical deformations. A quantitative understanding of the coupling behavior is the key to many applications. This paper formulates a nonlinear continuum model for lamellar gels by considering the constrained swelling and anisotropic deformation in both layers. A finite-element method is further developed to simulate the mechanochromatic response of a lamellar gel undergoing a nonuniform field.

  18. Effects Of Stress On Bone-Formation Markers In Rats

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Fung, Paul; Vasques, Marilyn; Grindeland, Richard E.; Patterson-Buckendahl, Patricia; Durnova, Galina

    1992-01-01

    Report describes experiments involving simultaneous measurement of concentrations, in blood, of two substances indicative of formation of bone in rats. Measurements performed after flight in outer space plus 48 h of postflight environmental stress. Results emphasize critical influences of adrenal status and diet on functions of osteoblasts.

  19. Serum albumin coating of demineralized bone matrix results in stronger new bone formation.

    PubMed

    Horváthy, Dénes B; Vácz, Gabriella; Szabó, Tamás; Szigyártó, Imola C; Toró, Ildikó; Vámos, Boglárka; Hornyák, István; Renner, Károly; Klára, Tamás; Szabó, Bence T; Dobó-Nagy, Csaba; Doros, Attila; Lacza, Zsombor

    2016-01-01

    Blood serum fractions are hotly debated adjuvants in bone replacement therapies. In the present experiment, we coated demineralized bone matrices (DBM) with serum albumin and investigated stem cell attachment in vitro and bone formation in a rat calvaria defect model. In the in vitro experiments, we observed that significantly more cells adhere to the serum albumin coated DBMs at every time point. In vivo bone formation with albumin coated and uncoated DBM was monitored biweekly by computed tomography until 11 weeks postoperatively while empty defects served as controls. By the seventh week, the bone defect in the albumin group was almost completely closed (remaining defect 3.0?±?2.3%), while uncoated DBM and unfilled control groups still had significant defects (uncoated: 40.2?±?9.1%, control: 52.4?±?8.9%). Higher density values were also observed in the albumin coated DBM group. In addition, the serum albumin enhanced group showed significantly higher volume of newly formed bone in the microCT analysis and produced significantly higher breaking force and stiffness compared to the uncoated grafts (peak breaking force: uncoated: 15.7?±?4 N, albumin 46.1?±?11 N). In conclusion, this investigation shows that implanting serum albumin coated DBM significantly reduces healing period in nonhealing defects and results in mechanically stronger bone. These results also support the idea that serum albumin coating provides a convenient milieu for stem cell function, and a much improved bone grafting success can be achieved without the use of exogenous stem cells. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 126-132, 2016. PMID:25677203

  20. Progressive Ankylosis Protein (ANK) in Osteoblasts and Osteoclasts Controls Bone Formation and Bone Remodeling

    PubMed Central

    Kim, Hyon Jong; Minashima, Takeshi; McCarthy, Edward F; Winkles, Jeffrey A; Kirsch, Thorsten

    2010-01-01

    The progressive ankylosis gene (ank) encodes a transmembrane protein that transports intracellular inorganic pyrophosphate (PPi) to the extracellular milieu. ank/ank mice, which express a truncated nonfunctional ANK, showed a markedly reduced bone mass, bone-formation rate, and number of tartrate-resistant acid phosphatase–positive (TRAP+) multinucleated osteoclasts. ANK function deficiency suppressed osteoblastic differentiation of ank/ank bone marrow stromal cells, as indicated by the decrease in the expression of bone marker genes, including osterix, reduced alkaline phosphatase activity, and mineralization. Runx2 gene expression levels were not altered. Conversely, overexpression of ANK in the preosteoblastic cell line MC3T3-E1 resulted in increased expression of bone marker genes, including osterix. Whereas runx2 expression was not altered in ANK-overexpressing MC3T3-E1 cells, runx2 transcriptional activity was increased. Extracellular PPi or Pi stimulated osteoblastogenic differentiation of MC3T3-E1 cells or partially rescued delayed osteoblastogenic differentiation of ank/ank bone marrow stromal cells. A loss of PPi transport function ANK mutation also stimulated osteoblastogenic differentiation of MC3T3-E1 cells. Furthermore, ANK function deficiency suppressed the formation of multinucleated osteoclasts from ank/ank bone marrow cells cultured in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-?B ligand. In conclusion, ANK is a positive regulator of osteoblastic and osteoclastic differentiation events toward a mature osteoblastic and osteoclastic phenotype. © 2010 American Society for Bone and Mineral Research. PMID:20200976

  1. Surface microcracks signal osteoblasts to regulate alignment and bone formation

    PubMed Central

    Shu, Yutian; Baumann, Melissa J.; Case, Eldon D.; Irwin, Regina K.; Meyer, Sarah E.; Pearson, Craig S.; McCabe, Laura R.

    2014-01-01

    Microcracks are present in bone and can result from fatigue damage due to repeated, cyclically applied stresses. From a mechanical point, microcracks can dissipate strain energy at the advancing tip of a crack to improve overall bone toughness. Physiologically, microcracks are thought to trigger bone remodeling. Here, we examine the effect of microcracks specifically on osteoblasts, which are bone-forming cells, by comparing cell responses on microcracked versus non-microcracked hydroxyapatite (HA) specimens. Osteoblast attachment was found to be greater on microcracked HA specimens (p<0.05). More importantly, we identified the preferential alignment of osteoblasts in the direction of the microcracks on HA. Cells also displayed a preferential attachment that was 75 to 90 ?m away from the microcrack indent. After 21 days of culture, osteoblast maturation was notably enhanced on the HA with microcracks, as indicated by increased alkaline phosphatase activity and gene expression. Furthermore, examination of bone deposition by confocal laser scanning microscope indicated preferential mineralization at microcrack indentation sites. Dissolution studies indicate that the microcracks increase calcium release, which could contribute to osteoblast responses. Our findings suggest that microcracks signal osteoblast attachment and bone formation/healing. PMID:25280696

  2. Transgenic overexpression of bone morphogenetic protein 11 propeptide in skeleton enhances bone formation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression...

  3. Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis

    PubMed Central

    Lories, Rik JU; Luyten, Frank P; de Vlam, Kurt

    2009-01-01

    Targeted therapies that neutralize tumour necrosis factor are often able to control the signs and symptoms of spondyloarthritis. However, recent animal model data and clinical observations indicate that control of inflammation may not be sufficient to impede disease progression toward ankylosis in these patients. Bone morphogenetic proteins and WNTs (wingless-type like) are likely to play an important role in ankylosis and could be therapeutic targets. The relationship between inflammation and new bone formation is still unclear. This review summarizes progress made in our understanding of ankylosis and offers an alternative view of the relationship between inflammation and ankylosis. PMID:19439035

  4. Control of bone formation by the serpentine receptor Frizzled-9

    PubMed Central

    Albers, Joachim; Schulze, Jochen; Beil, F. Timo; Gebauer, Matthias; Baranowsky, Anke; Keller, Johannes; Marshall, Robert P.; Wintges, Kristofer; Friedrich, Felix W.; Priemel, Matthias; Schilling, Arndt F.; Rueger, Johannes M.; Cornils, Kerstin; Fehse, Boris; Streichert, Thomas; Sauter, Guido; Jakob, Franz; Insogna, Karl L.; Pober, Barbara; Knobeloch, Klaus-Peter; Francke, Uta; Amling, Michael

    2011-01-01

    Although Wnt signaling in osteoblasts is of critical importance for the regulation of bone remodeling, it is not yet known which specific Wnt receptors of the Frizzled family are functionally relevant in this process. In this paper, we show that Fzd9 is induced upon osteoblast differentiation and that Fzd9?/? mice display low bone mass caused by impaired bone formation. Our analysis of Fzd9?/? primary osteoblasts demonstrated defects in matrix mineralization in spite of normal expression of established differentiation markers. In contrast, we observed a reduced expression of chemokines and interferon-regulated genes in Fzd9?/? osteoblasts. We also identified the ubiquitin-like modifier Isg15 as one potential downstream mediator of Fzd9 in these cells. Importantly, our molecular analysis further revealed that canonical Wnt signaling is not impaired in the absence of Fzd9, thus explaining the absence of a bone resorption phenotype. Collectively, our results reveal a previously unknown function of Fzd9 in osteoblasts, a finding that may have therapeutic implications for bone loss disorders. PMID:21402791

  5. Multi-protein Delivery by Nanodiamonds Promotes Bone Formation

    PubMed Central

    Moore, L.; Gatica, M.; Kim, H.; Osawa, E.; Ho, D.

    2013-01-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE® for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

  6. Bone Tissue Engineering with Multilayered Scaffolds-Part II: Combining Vascularization with Bone Formation in Critical-Sized Bone Defect.

    PubMed

    Sathy, Binulal Nelson; Watson, Brendan M; Kinard, Lucas A; Spicer, Patrick P; Dahlin, Rebecca L; Mikos, Antonios G; Nair, Shantikumar

    2015-10-01

    Our previous in vivo study showed that multilayered scaffolds made of an angiogenic layer embedded between an osteogenic layer and an osteoconductive layer, with layer thickness in the 100-400??m range, resulted in through-the-thickness vascularization of the construct even in the absence of exogenous endothelial cells. The angiogenic layer was a collagen-fibronectin gel, and the osteogenic layer was made from nanofibrous polycaprolactone while the osteoconductive layer was made either from microporous hydroxyapatite or microfibrous polycaprolactone. In this follow-up study, we implanted these acellular and cellular multilayered constructs in critical-sized rat calvarial defects and evaluated their vascularization and bone formation potential. Vascularization and bone formation at the defect were evaluated and quantified using microcomputed tomography (microCT) followed by perfusion of the animals with the radio opaque contrast agent, MICROFIL. The extent of bony bridging and union within the critical-sized defect was evaluated using a previously established scoring system from the microCT data set. Similarly the new bone formation in the defect was quantified from the microCT data set as previously reported. Histological evaluation at 4 and 12 weeks validated the microCT findings. Our experimental results showed that acellular multilayered scaffolds with microscale-thick nanofibers and porous ceramic discs with angiogenic zone at their interface can regenerate functional vasculature and bone similar to that of cellular constructs in critical-sized calvarial defects. This result suggests that suitably bioengineered acellular multilayered constructs can be an improved and more translational approach in functional in vivo bone regeneration. PMID:26262560

  7. Morphological instabilities of lamellar eutectics

    NASA Astrophysics Data System (ADS)

    Karma, Alain; Sarkissian, Armand

    1996-03-01

    We present the results of a numerical study based on the boundary integral technique of interfacial pattern formation in directional solidification of thin-film lamellar eutectics at low velocity. Microstructure selection maps that identify the stability domains of various steady-state and nonsteady-state growth morphologies in the spacing-composition (? C 0) plane are constructed for the transparent organic alloy CBr4-C2Cl6 and for a model eutectic alloy with two solid phases of identical physical properties. In CBr4-C2Cl6, the basic set of instabilities that limit steady-state growth is richer than expected. It consists of three primary instabilities, two of which are oscillatory, which bound the domain of the commonly observed axisymmetric lamellar morphology, and two secondary oscillatory instabilities, which bound the domain of the nonaxisymmetric (tilted) lamellar morphology. The latter is predicted to occur over a hypereutectic range of composition which coincides well with experiment. Moreover, the steady tilt bifurcation lies between but does not directly bound either of these two domains, which are consequently disjoint. Four stable oscillatory microstructures, at least three of which have been seen experimentally, are predicted to occur in unstable regimes. In the model alloy, the structure is qualitatively similar, except that a stable domain of tilted steady-state growth is not found, in agreement with previous random-walk simulations. Furthermore, the composition range of stability of the axisymmetric morphology decreases sharply with increasing spacing away from minimum undercooling but extends further off-eutectic than predicted by the competitive growth criterion. In addition, oscillations with a wavelength equal to two ? lead to lamella termination at a small distance above the onset of instability. The implications of these two features for the eutectic to dendrite transition are examined with the conclusion that in the absence of heterogeneous nucleation, this transition should be histeritic at small velocity and temperature gradient.

  8. Direct bone formation during distraction osteogenesis does not require TNF alpha receptors and elevated serum TNF alpha fails to inhibit bone formation in TNFR1 deficient mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Distraction osteogenesis (DO) is a process which induces direct new bone formation as a result of mechanical distraction. Tumor necrosis factor-alpha (TNF) is a cytokine that can modulate osteoblastogenesis. The direct effects of TNF on direct bone formation in rodents are hypothetically mediated th...

  9. Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus

    USGS Publications Warehouse

    Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

    2003-01-01

    Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

  10. The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

    PubMed Central

    Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

    2013-01-01

    Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

  11. Ursolic acid incorporation does not prevent the formation of a non-lamellar phase in pH-sensitive and long-circulating liposomes.

    PubMed

    Lopes, Sávia C A; Novais, Marcus V M; Ferreira, Diêgo S; Braga, Fernão C; Magalhães-Paniago, Rogério; Malachias, Ângelo; Oliveira, Mônica C

    2014-12-23

    Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low water solubility, which limits its biological applications. In this context, our research group has proposed the incorporation of UA in long-circulating and pH-sensitive liposomes (SpHL-UA).These liposomes, composed of dioleylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethylene glycol2000 (DSPE-PEG2000), were shown to be very promising carriers for UA. Considering that the release of UA from SpHL-UA and its antitumor activity depend upon the occurrence of the lamellar to non-lamellar phase transition of DOPE, in the present work, the interactions of UA with the components of the liposomes were evaluated, aiming to clarify their role in the structural organization of DOPE. The study was carried out by differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) under low hydration conditions. DSC studies revealed that DOPE phase transition temperatures did not shift significantly upon UA addition. On the other hand, in SAXS studies, a different pattern of DOPE phase organization was observed in the presence of UA, with the occurrence of the cubic phase Im3m at 20 °C and the cubic phase Pn3m at 60 °C. These findings suggest that UA interacts with the lipids and changes their self-assembly. However, these interactions between the lipids and UA were unable to eliminate the lamellar to non-lamellar phase transition, which is essential for the cytoplasmic delivery of UA molecules from SpHL-UA. PMID:25490253

  12. Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation.

    PubMed

    Coe, Lindsay M; Tekalur, Srinivasan Arjun; Shu, Yutian; Baumann, Melissa J; McCabe, Laura R

    2015-08-01

    Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Previous studies demonstrate that T1-diabetes decreases osteoblast activity and viability. Bisphosphonate therapy, commonly used to treat osteoporosis, is demonstrated to inhibit osteoclast activity as well as osteoblast apoptosis. Therefore, we examined the effect of weekly alendronate treatments on T1-diabetes induced osteoblast apoptosis and bone loss. Bone TUNEL assays identified that alendronate therapy prevents the diabetes-induced osteoblast death observed during early stages of diabetes development. Consistent with this, alendronate treatment for 40 days was able to prevent diabetes-induced trabecular bone loss. Alendronate was also able to reduce marrow adiposity in both control diabetic mice compared to untreated mice. Mechanical testing indicated that 40 days of alendronate treatment increased bone stiffness but decreased the work required for fracture in T1-diabetic and alendronate treated mice. Of concern at this later time point, bone formation rate and osteoblast markers, which were already decreased in diabetic mice, were further suppressed in alendronate-treated diabetic mice. Taken together, our results suggest that short-term alendronate treatment can prevent T1-diabetes-induced bone loss in mice, possibly in part by inhibiting diabetes onset associated osteoblast death, while longer treatment enhanced bone density but at the cost of further suppressing bone formation in diabetic mice. PMID:25641511

  13. Carbon nanotubes functionalized with fibroblast growth factor accelerate proliferation of bone marrow-derived stromal cells and bone formation

    NASA Astrophysics Data System (ADS)

    Hirata, Eri; Ménard-Moyon, Cécilia; Venturelli, Enrica; Takita, Hiroko; Watari, Fumio; Bianco, Alberto; Yokoyama, Atsuro

    2013-11-01

    Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth factor (FGF) and the advantages of their use as scaffolds for bone augmentation were evaluated in vitro and in vivo. The activity of FGF was assessed by measuring the effect on the proliferation of rat bone marrow stromal cells (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF alone. In addition, FGF-CNT coated sponges were implanted between the parietal bone and the periosteum of rats and the formation of new bone was investigated. At day 14 after implantation, a larger amount of newly formed bone was clearly observed in most pores of FGF-CNT coated sponges. These findings indicated that MWCNTs accelerated new bone formation in response to FGF, as well as the integration of particles into new bone during its formation. Scaffolds coated with FGF-CNT could be considered as promising novel substituting materials for bone regeneration in future tissue engineering applications.

  14. Expression of PGK1 By Prostate Cancer Cells Induces Bone Formation

    PubMed Central

    Jung, Younghun; Shiozawa, Yusuke; Wang, Jianhua; Wang, Jingcheng; Wang, Zhuo; Pedersen, Elisabeth A.; Lee, Clara H.; Hall, Christopher L.; Hogg, Phillip J.; Krebsbach, Paul H.; Keller, Evan T.; Taichman, Russell S.

    2009-01-01

    Prostate cancer (PCa) is one of the solid tumors that metastasize to the bone. Once there, the phenotype of the bone lesions becomes depends upon the balance between osteoblastogenesis and osteoclastogenesis. We previously reported that over-expression of phosphoglycerate kinase 1 (PGK1) in PCa cell lines enhanced bone formation at the metastatic site in vivo. Here, the role of PGK1 in the bone formation was further explored. We demonstrate that PCa-derived PGK1 induces osteoblastic differentiation of bone marrow stromal cells. We also found that PGK1 secreted by PCa inhibits osteoclastogenesis. Finally, the expression levels of the bone specific markers in PCa cell themselves were higher in cells over expressing PGK1 than controls. Together, these data suggest that PGK1 secreted by PCa regulates bone formation at the metastatic site by increasing osteoblastic activity, decreasing osteoclastic function, and expressing an osteoblastic phenotype by PCa themselves. PMID:19825988

  15. Type XII collagen regulates osteoblast polarity and communication during bone formation

    PubMed Central

    Izu, Yayoi; Sun, Mei; Zwolanek, Daniela; Veit, Guido; Williams, Valerie; Cha, Byeong; Jepsen, Karl J.; Koch, Manuel

    2011-01-01

    Differentiated osteoblasts are polarized in regions of bone deposition, demonstrate extensive cell interaction and communication, and are responsible for bone formation and quality. Type XII collagen is a fibril-associated collagen with interrupted triple helices and has been implicated in the osteoblast response to mechanical forces. Type XII collagen is expressed by osteoblasts and localizes to areas of bone formation. A transgenic mouse null for type XII collagen exhibits skeletal abnormalities including shorter, more slender long bones with decreased mechanical strength as well as altered vertebrae structure compared with wild-type mice. Col12a?/? osteoblasts have decreased bone matrix deposition with delayed maturation indicated by decreased bone matrix protein expression. Compared with controls, Col12a?/? osteoblasts are disorganized and less polarized with disrupted cell–cell interactions, decreased connexin43 expression, and impaired gap junction function. The data demonstrate important regulatory roles for type XII collagen in osteoblast differentiation and bone matrix formation. PMID:21670218

  16. Cell sheet-engineered bones used for the reconstruction of mandibular defects in an animal model

    PubMed Central

    DU, CHUNHUA; YAO, CHAO; LI, NINGYI; WANG, SHUANGYI; FENG, YUANYONG; YANG, XUECAI

    2015-01-01

    The aim of the present study was to investigate the generation of cell sheet-engineered bones used for the reconstruction of mandibular defects. Bone marrow stem cells (BMSCs) were cultured and induced to generate osteoblasts. Poly(lactic-co-glycolic acid) (PLGA) scaffolds were wrapped with or without cell sheets and then implanted into dogs with mandibular defects in the right side (experimental group) or the left side (control group), respectively. Subsequently, X-ray analyses, and hematoxylin and eosin staining were performed at various time points (at 4, 8, 12 or 16 weeks post-implantation; n=4 at each time point). The osteogenesis in the experimental group was significantly improved compared with that in the control group. At 16 weeks after implantation, numerous Haversian systems and a few lamellar bones were observed at the periphery. In the control group, the engineered bone (without BMSC sheets) presented fewer Haversian systems and no lamellar bones. The optical density of the fresh bone in the experimental group was significantly higher compared with that in the control group (P<0.05). In conclusion, tissue-engineered bone with the structure of lamellar bones can be generated using BMSC sheets and implantation of these bones had an improved effects compared with the control group. Cell sheet transplantation was found to enhance bone formation at the reconstruction site of the mandibular defects. PMID:26668619

  17. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

  18. Lamellar eutectic growth with anisotropic interphase boundaries

    NASA Astrophysics Data System (ADS)

    Akamatsu, S.; Bottin-Rousseau, S.; Faivre, G.; Ghosh, S.; Plapp, M.

    2015-06-01

    We present a numerical study of the effect of a free-energy anisotropy of the solid- solid interphase boundaries on the formation of tilted lamellar microstructures during directional solidification of nonfaceted binary eutectic alloys. We used two different methods - phase-field (PF) and dynamic boundary-integral (BI) - to simulate the growth of periodic eutectic patterns in two dimensions. For a given Wulff plot of the interphase boundary, which characterizes a eutectic grain with a given relative orientation of the two solid phases, the lamellar tilt angle depends on the angle between the thermal axis z and a reference crystallographic axis. Both PF and BI results confirm the general validity of a recent approximate theory which assumes that, at the trijunctions, the surface tension vector of the interphase boundary is parallel to z. In particular, a crystallographic locking of the lamellae onto a direction close to a deep minimum in the Wulff plot is well reproduced in the simulations.

  19. A new approach to enhancement of bone formation by electrically polarized hydroxyapatite.

    PubMed

    Teng, N C; Nakamura, S; Takagi, Y; Yamashita, Y; Ohgaki, M; Yamashita, K

    2001-10-01

    An electrical field may affect osteogenesis. Since we found that hydroxyapatite (HA) ceramics may be polarizable, we hypothesized that electrically polarized HA may foster production of new bone in vivo. Both polarized and non-polarized HA ceramics were inserted into the subperiosteum spaces at the parietal bone area of rats. After 2, 4, and 8 weeks, the implant sites were examined histologically. Morphometric analysis revealed that new bone formation was accelerated on the negatively charged surface of the polarized HA (N-surface) at 2 weeks. The newly formed bone approached maturation at 4 weeks and was thicker on the N-surface than in the controls. By 8 weeks, newly formed bone in the controls was almost the same as that on the N-surface. These findings suggest that polarized HA is biocompatible and that bone formation on the N-surface is enhanced in the early stage of bone healing. PMID:11706953

  20. Calcium ions and osteoclastogenesis initiate the induction of bone formation by coral-derived macroporous constructs

    PubMed Central

    Klar, Roland M; Duarte, Raquel; Dix-Peek, Therese; Dickens, Caroline; Ferretti, Carlo; Ripamonti, Ugo

    2013-01-01

    Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) initiate the induction of bone formation. Which are the molecular signals that initiate pattern formation and the induction of bone formation? To evaluate the role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded with either 500 ?g of the calcium channel blocker, verapamil hydrochloride, or 240 ?g of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On day 15, up-regulation of type IV collagen characterized all the implanted constructs correlating with vascular invasion. Zoledronate-treated specimens showed an important delay in tissue patterning and morphogenesis with limited bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation by induction. 7% HA/CC pre-loaded with the Ca++ channel blocker verapamil hydrochloride strongly inhibited the induction of bone formation. Down-regulation of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin genes correlated with limited bone formation in 7% HA/CC pre-loaded with either verapamil or zoledronate, indicating that the induction of bone formation by coral-derived macroporous constructs is via the BMPs pathway. The spontaneous induction of bone formation is initiated by a local peak of Ca++ activating stem cell differentiation and the induction of bone formation. PMID:24106923

  1. Radiostrontium clearance and bone formation in response to simulated internal screw fixation

    SciTech Connect

    Daum, W.J.; Simmons, D.J.; Fenster, R.; Shively, R.A.

    1987-06-01

    Changes in radiostrontium clearance (SrC) and bone formation (tetracycline labeling) were observed in the femurs of skeletally mature dogs following the various operative steps involved in bone screw fixation. Drilling, but not periosteal stripping, produced a small but statistically significant increase in SrC and endosteal bone formation in the distal third of the bone. Strontium clearance values equivalent to those produced by drilling alone were recorded after screw fixation at low or high torque (5 versus 20 inch pounds), as well as by the insertion of loosely fitting stainless steel implants. Bone formation (equals the percentage tetracycline-labeled trabecular bone surfaces) was increased by 30% when SrC values exceeded 3.5 ml/100 g bone/min, and the relationship was linear when SrC values ranged between 1.0 and 7.0 ml/100 g bone/min. The changes in SrC and bone formation one-week after bone screw application are primarily those associated with a response to local trauma caused by drilling.

  2. Bone marrow-derived osteoblast progenitor cells in circulating blood contribute to ectopic bone formation in mice

    SciTech Connect

    Otsuru, Satoru; Tamai, Katsuto . E-mail: tamai@gts.med.osaka-u.ac.jp; Yamazaki, Takehiko; Yoshikawa, Hideki; Kaneda, Yasufumi

    2007-03-09

    Recent studies have suggested the existence of osteoblastic cells in the circulation, but the origin and role of these cells in vivo are not clear. Here, we examined how these cells contribute to osteogenesis in a bone morphogenetic protein (BMP)-induced model of ectopic bone formation. Following lethal dose-irradiation and subsequent green fluorescent protein-transgenic bone marrow cell-transplantation (GFP-BMT) in mice, a BMP-2-containing collagen pellet was implanted into muscle. Three weeks later, a significant number of GFP-positive osteoblastic cells were present in the newly generated ectopic bone. Moreover, peripheral blood mononuclear cells (PBMNCs) from the BMP-2-implanted mouse were then shown to include osteoblast progenitor cells (OPCs) in culture. Passive transfer of the PBMNCs isolated from the BMP-2-implanted GFP-mouse to the BMP-2-implanted nude mouse led to GFP-positive osteoblast accumulation in the ectopic bone. These data provide new insight into the mechanism of ectopic bone formation involving bone marrow-derived OPCs in circulating blood.

  3. Cadmium stimulates osteoclast-like multinucleated cell formation in mouse bone marrow cell cultures

    SciTech Connect

    Miyahara, Tatsuro; Takata, Masakazu; Miyata, Masaki; Nagai, Miyuki; Sugure, Akemi; Kozuka, Hiroshi; Kuze, Shougo )

    1991-08-01

    Most of cadmium (Cd)-treated animals have been reported to show osteoporosis-like changes in bones. This suggests that Cd may promote bone loss by a direct action on bone. It was found that Cd stimulated prostaglandin E{sub 2}(PGE{sub 2}) production in the osteoblast-like cell, MC3T3-E1. Therefore, Cd stimulates bone resorption by increasing PGE{sub 2} production. Recently, several bone marrow cell culture systems have been developed for examining the formation of osteoclast-like multinucleated cells in vitro. As osteoblasts produce PGE{sub 2} by Cd-induced cyclooxygenase and may play an important role in osteoclast formation, the present study was undertaken to clarify the possibility that Cd might stimulate osteoclast formation in a mouse bone marrow culture system.

  4. Alendronate promotes bone formation by inhibiting protein prenylation in osteoblasts in rat tooth replantation model.

    PubMed

    Komatsu, Koichiro; Shimada, Akemi; Shibata, Tatsuya; Wada, Satoshi; Ideno, Hisashi; Nakashima, Kazuhisa; Amizuka, Norio; Noda, Masaki; Nifuji, Akira

    2013-11-01

    Bisphosphonates (BPs) are a major class of antiresorptive drug, and their molecular mechanisms of antiresorptive action have been extensively studied. Recent studies have suggested that BPs target bone-forming cells as well as bone-resorbing cells. We previously demonstrated that local application of a nitrogen-containing BP (N-BP), alendronate (ALN), for a short period of time increased bone tissue in a rat tooth replantation model. Here, we investigated cellular mechanisms of bone formation by ALN. Bone histomorphometry confirmed that bone formation was increased by local application of ALN. ALN increased proliferation of bone-forming cells residing on the bone surface, whereas it suppressed the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Moreover, ALN treatment induced more alkaline phosphatase-positive and osteocalcin-positive cells on the bone surface than PBS treatment. In vitro studies revealed that pulse treatment with ALN promoted osteocalcin expression. To track the target cells of N-BPs, we applied fluorescence-labeled ALN (F-ALN) in vivo and in vitro. F-ALN was taken into bone-forming cells both in vivo and in vitro. This intracellular uptake was inhibited by endocytosis inhibitors. Furthermore, the endocytosis inhibitor dansylcadaverine (DC) suppressed ALN-stimulated osteoblastic differentiation in vitro and it suppressed the increase in alkaline phosphatase-positive bone-forming cells and subsequent bone formation in vivo. DC also blocked the inhibition of Rap1A prenylation by ALN in the osteoblastic cells. These data suggest that local application of ALN promotes bone formation by stimulating proliferation and differentiation of bone-forming cells as well as inhibiting osteoclast function. These effects may occur through endocytic incorporation of ALN and subsequent inhibition of protein prenylation. PMID:24096963

  5. Effect of culture conditions and calcium phosphate coating on ectopic bone formation.

    PubMed

    Vaquette, Cédryck; Ivanovski, Saso; Hamlet, Stephen M; Hutmacher, Dietmar W

    2013-07-01

    This study investigated the effect of a calcium phosphate (CaP) coating onto a polycaprolactone melt electrospun scaffold and in vitro culture conditions on ectopic bone formation in a subcutaneous rat model. The CaP coating resulted in an increased alkaline phosphatase activity (ALP) in ovine osteoblasts regardless of the culture conditions and this was also translated into higher levels of mineralisation. A subcutaneous implantation was performed and increasing ectopic bone formation was observed over time for the CaP-coated samples previously cultured in osteogenic media whereas the corresponding non-coated samples displayed a lag phase before bone formation occurred from 4 to 8 weeks post-implantation. Histology and immunohistochemistry revealed bone fill through the scaffolds 8 weeks post-implantation for coated and non-coated specimens and that ALP, osteocalcin and collagen 1 were present at the ossification front and in the bone tissues. Vascularisation in the vicinity of the bone tissues was also observed indicating that the newly formed bone was not deprived of oxygen and nutrients. We found that in vitro osteogenic induction was essential for achieving bone formation and CaP coating accelerated the osteogenic process. We conclude that high cell density and preservation of the collagenous and mineralised extracellular matrix secreted in vitro are factors of importance for ectopic bone formation. PMID:23623428

  6. Effect of Alendronate on Bone Formation during Tooth Extraction Wound Healing.

    PubMed

    Tanoue, R; Koi, K; Yamashita, J

    2015-09-01

    Alendronate (ALN) is an antiresorptive agent widely used for the treatment of osteoporosis. Its suppressive effect on osteoclasts has been extensively studied. However, the effect of ALN on bone formation is not as clear as its effect on resorption. The objective was to determine the effect of short-term ALN on bone formation and tooth extraction wound healing. Molar tooth extractions were performed in mice. ALN, parathyroid hormone (PTH), or saline (vehicle control) was administered. PTH was used as the bone anabolic control. Mice were euthanized at 3, 5, 7, 10, and 21 d after extractions. Hard tissue healing was determined histomorphometrically. Neutrophils and lymphatic and blood vessels were quantified to evaluate soft tissue healing. Gene expression in the wounds was assessed at the RNA level. Furthermore, the vossicle bone transplant system was used to verify findings from extraction wound analysis. Alkaline phosphatase (ALP) was visualized in the vossicles to assess osteoblast activity. ALN exhibited no negative effect on bone formation. In intact tibiae, ALN increased bone mass significantly more than PTH did. Consistently, significantly elevated osteoblast numbers were noted. In the extraction sockets, bone fill in the ALN-treated mice was equivalent to the control. Genes associated with bone morphogenetic protein signaling, such as bmp2, nog, and dlx5, were activated in the extraction wounds of the ALN-treated animals. Bone formation in vossicles was significantly enhanced in the ALN versus PTH group. In agreement with this, ALN upregulated ALP activity considerably in vossicles. Neutrophil aggregation and suppressed lymphangiogenesis were evident in the soft tissue at 21 d after extraction, although gross healing of extraction wounds was uneventful. Bone formation was not impeded by short-term ALN treatment. Rather, short-term ALN treatment enhanced bone formation. ALN did not alter bone fill in extraction sockets. PMID:26124220

  7. Treatment with the combination of ibandronate plus eldecalcitol has a synergistic effect on inhibition of bone resorption without suppressing bone formation in ovariectomized rats.

    PubMed

    Sakai, Sadaoki; Takeda, Satoshi; Sugimoto, Masanori; Shimizu, Masaru; Shimonaka, Yasushi; Yogo, Kenji; Hashimoto, Junko; Bauss, Frieder; Endo, Koichi

    2015-12-01

    Bisphosphonates are widely used in the treatment of osteoporosis and contribute to the reduction of bone fractures. Ibandronate (IBN) is a highly potent, nitrogen-containing bisphosphonate, which is administered orally or intravenously at extended dosing intervals. Vitamin D or active vitamin D3 derivatives are also used in the treatment of osteoporosis, and are often used in combination with other drugs. In this study, we investigated the effect of treatment with the combination of once-monthly s.c. dosing of IBN plus once-daily oral eldecalcitol (ELD), an active vitamin D3 derivative, using aged ovariectomized (OVX) rats. Treatment was started the day after OVX, and analyses were performed 4, 8, and 12weeks thereafter by determination of bone markers, bone mineral density, biomechanical properties, and histomorphometry. The combination treatment showed a synergistic effect in increasing both lumbar and femoral BMD, and resulted in a significant increase in bone ultimate load. The combination of IBN plus ELD acted synergistically to reduce bone resorption, whereas bone formation did not decrease any more than with monotherapy with either IBN or ELD. Bone formation independent of bone resorption (a process known as 'minimodeling') was not changed in vehicle treated OVX rats despite the increase in bone turnover. ELD upregulated minimodeling, which was however not diminished in the combination treatment. In conclusion, treatment with the combination of IBN plus ELD was beneficial in the treatment of osteoporosis in aged OVX rats. It exhibited a synergistic inhibitory effect on bone resorption and keeps bone formation at the level of sham controls. This uncoupling of bone resorption/bone formation was affected, to some extent, by minimodeling-based bone formation which is independent of bone resorption. This combination regimen which showed synergistic effect on BMD and bone ultimate load without inhibition of bone formation may be beneficial in long-term osteoporosis treatment to prevent bone fractures. PMID:26281770

  8. Impact of skeletal unloading on bone formation: Role of systemic and local factors

    NASA Astrophysics Data System (ADS)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  9. Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.

    PubMed

    Schulze, Jochen; Seitz, Sebastian; Saito, Hiroaki; Schneebauer, Michael; Marshall, Robert P; Baranowsky, Anke; Busse, Bjoern; Schilling, Arndt F; Friedrich, Felix W; Albers, Joachim; Spiro, Alexander S; Zustin, Jozef; Streichert, Thomas; Ellwanger, Kristina; Niehrs, Christof; Amling, Michael; Baron, Roland; Schinke, Thorsten

    2010-01-01

    Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders. PMID:20436912

  10. Negative Regulation of Bone Formation by the Transmembrane Wnt Antagonist Kremen-2

    PubMed Central

    Schneebauer, Michael; Marshall, Robert P.; Baranowsky, Anke; Busse, Bjoern; Schilling, Arndt F.; Friedrich, Felix W.; Albers, Joachim; Spiro, Alexander S.; Zustin, Jozef; Streichert, Thomas; Ellwanger, Kristina; Niehrs, Christof; Amling, Michael; Baron, Roland; Schinke, Thorsten

    2010-01-01

    Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders. PMID:20436912

  11. Short-term aluminum administration in the rat: reductions in bone formation without osteomalacia

    SciTech Connect

    Goodman, W.G.

    1984-05-01

    Aluminum may be a pathogenic factor in dialysis-associated osteomalacia. To study the early effects of Al on bone, cortical bone growth was measured in pair-fed rats given Al and control rats over two consecutive intervals of 28 (period I) and 16 (period II) days, respectively, using tetracycline labeling of bone. Al (2 mg elemental Al per rat) was administered intraperitoneally for 5 days each week, except for the first week of study, when an incremental dose of Al was given. Control rats received saline vehicle only. For the entire 44-day study, bone and matrix formation were reduced from control values in rats given Al. Although bone and matrix formation remained at control levels during period I in rats given Al, both measurements decreased from control values during period II. During Al exposure, bone and matrix apposition at the periosteum were reduced from control levels in period II, but not in period I. Neither osteoid width nor mineralization front width increased from control values in rats given Al. These findings indicate that Al reduces bone and matrix formation early in the course of Al exposure and prior to the development of histologic osteomalacia. Rather than acting as an inhibitor of mineralization, the early effect of Al on bone is the suppression of matrix synthesis. Our results suggest that the state of low bone formation seen in dialysis-associated osteomalacia may be the consequence of a direct toxic effect of Al on the cellular activity of osteoblasts. 29 references, 3 tables.

  12. A Study of the Role of Nell-1 Gene Modified Goat Bone Marrow Stromal Cells in Promoting New Bone Formation

    PubMed Central

    Aghaloo, Tara; Jiang, Xinquan; Soo, Chia; Zhang, Zhiyuan; Zhang, Xiuli; Hu, Jingzhou; Pan, Hongya; Hsu, Tiffany; Wu, Benjamin; Ting, Kang; Zhang, Xinli

    2009-01-01

    Nell-1 is a recently discovered secreted protein with the capacity to promote osteoblastic calvarial cell differentiation and mineralization and induce calvarial bone overgrowth and regeneration in various rodent models. However, the extent of Nell-1 osteoinductivity in large animal cells remains unknown. The objective of the study was to evaluate the feasibility of adenoviral encoding Nell-1 (AdNell-1) gene transfer into primary adult goat bone marrow stromal cells (BMSCs) in vitro and in vivo and to compare the osteoinductive effects with those produced by bone morphogenetic protein-2 (BMP-2), a well established osteoinductive molecule currently utilized for regional gene therapy. AdNell-1-transduced BMSCs expressed Nell-1 protein and underwent osteoblastic differentiation within 2 weeks in vitro, which is comparable to AdBMP-2. After intramuscular injection of nude mice, the AdNell-1- and AdBMP-2-transduced BMSCs revealed new bone formation, while untransduced or AdLacZ-transduced BMSCs showed mainly fibrotic tissue proliferation. At 4 weeks, BMP-2 induced significantly larger bone mass with a mature bone margin and central cavity filled with primarily fatty marrow tissue. Nell-1 samples had significantly less bone mass but were histologically similar to newly formed trabecular bone mixed with chondroid bone-like areas verified by type X collagen (ColX) immunohistochemistry. This distinct difference in histomorphology from the bone mass induced by BMP-2 suggests that there is a potential clinical role/advantage for Nell-1 in skeletal tissue engineering and regeneration. PMID:17653100

  13. In vitro BMP2 stimulation of osteoblast citrate production in concert with mineralized bone nodule formation

    PubMed Central

    Costello, Leslie C.; Chellaiah, Meenakshi A.; Zou, Jing; Reynolds, Mark A.; Franklin, Renty B.

    2015-01-01

    Background That citrate is a major indispensible component of bone in humans and in all osteovertebrates has been known for about seventy-five years. Yet, its role and importance in the structure and function of bone and bone formation have remained unknown. However, recent studies have identified that citrate is a major and essential component of the apatite/collagen structure of bone; and that the biomechanical properties of bone (e.g., stability, strength, resistance to fracture) depend on the appropriate incorporation of citrate in the structure of bone. The osteoblasts have recently been identified as citrate-producing cells that provide the citrate that is incorporated in the apatite/collagen structure during osteogenesis. Little is known regarding the factors and mechanisms involved in the regulation of citrate that is incorporated along with mineralization during the process of bone formation. Because of the importance of BMP2 in the initiation of osteogenesis and the development of the osteoblasts, it is essential to determine its possible implication in the development of the citrate-producing capability of the osteoblasts (i.e., “citration”) during the formation of mineralized bone nodules. Methods The goal of this study was to determine if BMP2 promotes the development of citrate-producing osteoblasts for increased citrate incorporation in the formation of mineralized bone nodules. The study employed MC3T3 mesenchyme stem cell osteogenic differentiation in the presence and absence of BMP2. Results The results showed that BMP2 treatment increased the osteogenic development of mineralized bone nodules. In addition, BMP2 increased osteoblast citrate production and incorporation in the mineralized bone nodule. This was accompanied by increased ZIP1 transporter, which is an essential genetic/metabolic event for citrate-producing cells. Conclusions The results demonstrate, for the first time, that BMP2 facilitates the osteoblast “citration” process in concert with mineralization during bone formation; and provide confirmation of the important role of osteoblasts as specialized citrate-producing cells in the process of bone formation. However, it is essential to determine if these in vitro effects will occur in vivo in BMP2-implant induction of bone formation. “Citration” is essential for osteoinductive bone to represent the chemical, structural, and biomechanical properties of “normal” bone. PMID:26635961

  14. The Effect of Skeletal Unloading on Bone Formation: Role of IGF-I

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.; Kostenuik, P.; Holton, E. M.; Halloran, B. P.

    1999-01-01

    The best documented change in bone during space flight is the near cessation of bone formation. Space flight leads to a decrease in osteoblast number and activity, likely the result of altered differentiation of osteoblast precursors. The net result of these space flight induced changes is weaker bone. To understand the mechanism for these changes poses a challenge. Space flight studies must overcome enormous technical problems, and are necessarily limited in size and frequency. Therefore, ground based models have been developed to evaluate the effects of skeletal unloading. The hindlimb elevation (tail suspension) model simulates space flight better than other models because it reproduces the fluid shifts seen in space travel, is reversible, and is well tolerated by the animals with minimal evidence of stress as indicated by continued weight gain and normal levels and circadian rhythms of corticosterone. This is the model we have used for our experiments. Skeletal unloading by the hindlimb elevation method simulates a number of features of space flight in that bone formation, mineralization, and maturation are inhibited, osteoblast number is decreased, serum and skeletal osteocalcin levels fall, the ash content of bone decreases, and bone strength diminishes. We and others have shown that when osteoblasts or osteoprogenitor cells from the bones of the unloaded limbs are cultured in vitro they proliferate and differentiate more slowly, suggesting that skeletal unloading causes a persistent change in cell function which can be assessed in vitro. In contrast to the unweighted bones of the hindlimbs, no significant change in bone mass or bone formation is observed in the humeri, mandible, and cervical vertebrae during hindlimb elevation. The lack of effect of hindlimb elevation on bones like the humeri, mandible, and cervical vertebrae which are not unloaded by this procedure suggests that local factors rather than systemic effects dominate the response of bone to skeletal unloading. We have focussed on the role of IGF- 1 as the local factor mediating the effects of skeletal unloading on bone formation. IGF-I is produced by bone cells and chondrocytes; these cells have receptors for IGF-I, and respond to IGF-I with an increase in proliferation and function (e.g. collagen, and glycosaminoglycan production, respectively). IGF-I production by bone is under hormonal control, principally by GH and PTH, and IGF-I is thought to mediate some if not all of the effects of GH and PTH on bone growth. Thus, systemic changes in hormones such as GH and PTH may still have effects which vary from bone to bone depending on the loading history.

  15. FLUORIDE EFFECTS ON BONE FORMATION AND MINERALIZATION ARE INFLUENCED BY GENETICS

    PubMed Central

    Mousny, M.; Omelon, S.; Wise, L.; Everett, E. T.; Dumitriu, M.; Holmyard, D. P.; Banse, X.; Devogelaer, J. P.; Grynpas, M. D

    2008-01-01

    Introduction A variation in bone response to fluoride (F?) exposure has been attributed to genetic factors. Increasing fluoride doses (0ppm, 25ppm, 50ppm, 100ppm) for three inbred mouse strains with different susceptibilities to developing dental enamel fluorosis (A/J, a “susceptible” strain; SWR/J, an “intermediate” strain; 129P3/J, a “resistant” strain) had different effects on their cortical and trabecular bone mechanical properties. In this paper, the structural and material properties of the bone were evaluated to explain the previously observed changes in mechanical properties. Materials and Methods This study assessed the effect of increasing fluoride doses on the bone formation, microarchitecture, mineralization and microhardness of the A/J, SWR/J and 129P3/J mouse strains. Bone microarchitecture was quantified with microcomputed tomography and strut analysis. Bone formation was evaluated by static histomorphometry. Bone mineralization was quantified with backscattered electron (BSE) imaging and powder x-ray diffraction. Microhardness measurements were taken from the vertebral bodies (cortical and trabecular bone) and the cortex of the distal femur. Results Fluoride treatment had no significant effect on bone microarchitecture for any of the strains. All three strains demonstrated a significant increase in osteoid formation at the largest fluoride dose. Vertebral body trabecular bone BSE imaging revealed significantly decreased mineralization heterogeneity in the SWR/J strain at 50ppm and 100ppm F?. The trabecular and cortical bone mineralization profiles showed a non-significant shift towards higher mineralization with increasing F? dose in the three strains. Powder x-ray diffraction showed significantly smaller crystals for the 129P3/J strain, and increased crystal width with increasing F? dose for all strains. There was no effect of F? on trabecular and cortical bone microhardness. Conclusion Fluoride treatment had no significant effect on bone microarchitecture in these three strains. The increased osteoid formation and decreased mineralization heterogeneity support the theory that F? delays mineralization of new bone. The increasing crystal width with increasing F? dose confirms earlier results and correlates with most of the decreased mechanical properties. An increase in bone F? may affect the mineral-organic interfacial bonding and/or bone matrix proteins, interfering with bone crystal growth inhibition on the crystallite faces as well as bonding between the mineral and organic interface. The smaller bone crystallites of the 129P3/J (resistant) strain may indicate a stronger organic/inorganic interface, reducing crystallite growth rate and increasing interfacial mechanical strength. PMID:18755305

  16. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    PubMed Central

    Handra-Luca, Adriana; Dumuis-Gimenez, Marie-Laure; Bendib, Mouna; Anagnostis, Panagiotis

    2015-01-01

    Thyroid heterotopic bone formation (HBF) in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years). The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.). Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.). The number and size of HBFs (total: 28) ranged between 1 and 23/thyroid gland (one bilateral) and 1 and 10?mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular). The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp.) without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ?2?mm), and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated. PMID:26697239

  17. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis)

    PubMed Central

    McGee, Meghan E.; Maki, Aaron J.; Johnson, Steven E.; Lynne Nelson, O.; Robbins, Charles T.; Donahue, Seth W.

    2008-01-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis. PMID:18037367

  18. Circulating leptin is negatively associated with the isotopically-measured bone formation rate in pubertal adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Animal studies show that serum leptin (SL) is associated with decreased bone formation (BF) and increased bone resorption (BR) rates via its effects on the sympathetic nervous system. Pediatric data on these relationships are limited due to lack of accurate methodology for in vivo assess...

  19. The circadian modulation of leptin-controlled bone formation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mice with circadian gene Period and Cryptochrome mutations develop high bone mass early in life. Such a phenotype is accompanied by an increase in osteoblast numbers in mutant bone and cannot be corrected by leptin intracerebroventricular infusion. Thus, the molecular clock plays a key role in lepti...

  20. Regulation of bone resorption and formation by purines and pyrimidines

    E-print Network

    Burnstock, Geoffrey

    an organic collagen matrix, and three major cell types: osteoclasts, osteoblasts and osteocytes (Table 1; Fig. Some osteoblasts become incorporated in the bone matrix they secrete, differentiating into osteocytes Differentiate into osteocytes (network of strain- detecting cells) when engulfed by bone matrix; p

  1. Induction of bone formation in biphasic calcium phosphate scaffolds by bone morphogenetic protein-2 and primary osteoblasts.

    PubMed

    Strobel, L A; Rath, S N; Maier, A K; Beier, J P; Arkudas, A; Greil, P; Horch, R E; Kneser, U

    2014-03-01

    Bone tissue engineering strategies mainly depend on porous scaffold materials. In this study, novel biphasic calcium phosphate (BCP) matrices were generated by 3D-printing. High porosity was achieved by starch consolidation. This study aimed to characterise the porous BCP-scaffold properties and interactions of osteogenic cells and growth factors under in vivo conditions. Five differently treated constructs were implanted subcutaneously in syngeneic rats: plain BCP constructs (group A), constructs pre-treated with BMP-2 (group B; 1.6?µg BMP-2 per scaffold), seeded with primary osteoblasts (OB) (group C), seeded with OB and BMP-2 (group D) and constructs seeded with OB and pre-cultivated in a flow bioreactor for 6?weeks (group E). After 2, 4 and 6?weeks, specimens were explanted and subjected to histological and molecular biological analyses. Explanted scaffolds were invaded by fibrovascular tissue without significant foreign body reactions. Morphometric analysis demonstrated significantly increased bone formation in samples from group D (OB?+?BMP-2) compared to all other groups. Samples from groups B-E displayed significant mRNA expression of bone-specific genes after 6?weeks. Pre-cultivation in the flow bioreactor (group E) induced bone formation comparable with group B. In this study, differences in bone distribution between samples with BMP-2 or osteoblasts could be observed. In conclusion, combination of osteoblasts and BMP-2 synergistically enhanced bone formation in novel ceramic scaffolds. These results provide the basis for further experiments in orthotopic defect models with a focus on future applications in orthopaedic and reconstructive surgery. PMID:22740314

  2. Glycoprotein130 (Gp130)/interleukin-6 (IL-6) signalling in osteoclasts promotes bone formation in periosteal and trabecular bone.

    PubMed

    Johnson, Rachelle W; McGregor, Narelle E; Brennan, Holly J; Crimeen-Irwin, Blessing; Poulton, Ingrid J; Martin, T John; Sims, Natalie A

    2015-12-01

    Interleukin-6 (IL-6) and interleukin-11 (IL-11) receptors (IL-6R and IL-11R, respectively) are both expressed in osteoclasts and transduce signal via the glycoprotein130 (gp130) co-receptor, but the physiological role of this pathway is unclear. To determine the critical roles of gp130 signalling in the osteoclast, we generated mice using cathepsin K Cre (CtskCre) to disrupt gp130 signalling in osteoclasts. Bone marrow macrophages from CtskCre.gp130(f/f) mice generated more osteoclasts in vitro than cells from CtskCre.gp130(w/w) mice; these osteoclasts were also larger and had more nuclei than controls. While no increase in osteoclast numbers was observed in vivo, osteoclasts on trabecular bone surfaces of CtskCre.gp130(f/f) mice were more spread out than in control mice, but had no functional defect detectable by serum CTX1 levels or trabecular bone cartilage remnants. However, trabecular osteoblast number and mineralising surfaces were significantly lower in male CtskCre.gp130(f/f) mice compared to controls, and this was associated with a significantly lower trabecular bone volume at 12weeks of age. Furthermore, CtskCre.gp130(f/f) mice exhibited greatly suppressed periosteal bone formation at this age, indicated by significant reductions in both double-labelled surface and mineral apposition rate. By 26weeks of age, CtskCre.gp130(f/f) mice exhibited narrower femora, with lower periosteal and endocortical perimeters than CtskCre.gp130(w/w) controls. Since IL-6 and IL-11R global knockout mice exhibited a similar reduction in femoral width, we also assessed periosteal bone formation in those strains, and found bone forming surfaces were also reduced in male IL-6 null mice. These data suggest that IL-6/gp130 signalling in the osteoclast is not essential for normal bone resorption in vivo, but maintains both trabecular and periosteal bone formation in male mice by promoting osteoblast activity through the stimulation of osteoclast-derived "coupling factors" and "osteotransmitters", respectively. PMID:26255596

  3. Is suppression of bone formation during simulated weightlessness related to glucocorticoid levels

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E. R.; Bomalaski, M. D.; Enayati-Gordon, E.; Gonsalves, M. R.; Wronski, T. J.

    1982-01-01

    To investigate the hypothesis that suppression of bone formation in the suspended rat model was the result of increased levels of corticosterone, experiments were performed on young, growing, male rats exposed either to 4 C or suspended for two weeks. Rats suspended on the model system, designed to simulate certain aspects of spaceflight, gained weight at a rate at least equal to control animals but still showed a significant suppression of bone formation within 7 days. Cold-exposed rats gained less weight than their corresponding control group and did not demonstrate any suppression of bone formation. These findings suggest: (1) tail suspension is less stressful than previously used harness systems; (2) suspension in young, rapidly growing rats causes a significant suppression of cortical bone formation; (3) cold exposure does not alter bone formation rate in rats of a similar age and strain to those suspended in this study; and (4) suppression of bone formation provoked by unloading the rear limbs is not due solely to sustained stimulation of the pituitary-adrenal system.

  4. Effect of low gravity on calcium metabolism and bone formation (L-7)

    NASA Technical Reports Server (NTRS)

    Suda, Tatsuo

    1993-01-01

    Recently, attention has been focused on the disorders of bone and calcium metabolism during space flight. The skeletal system has evolved on the Earth under 1-g. Space flights under low gravity appear to cause substantial changes in bone and calcium homeostasis of the animals adapted to 1-g. A space experiment for the First Materials Processing Test (FMPT) was proposed to examine the effects of low gravity on calcium metabolism and bone formation using chick embryos loaded in a space shuttle. This space experiment was proposed based on the following two experimental findings. First, it has been reported that bone density decreases significantly during prolonged space flight. The data obtained from the US Skylab and the U.S.S.R. Salyut-6 cosmonauts have also documented that the degree of bone loss is related to the duration of space flight. Second, the US-Soviet joints space experiment demonstrated that the decrease in bone density under low gravity appears to be due to the decrease in bone formation rather than the increase in bone resorption. The purpose of our space experiment is, therefore, to investigate further the mechanisms of bone growth under low gravity using fertilized chick embryos.

  5. P2X7 receptors: role in bone cell formation and function.

    PubMed

    Agrawal, Ankita; Gartland, Alison

    2015-04-01

    The role of the P2X7 receptor (P2X7R) is being explored with intensive interest in the context of normal bone physiology, bone-related diseases and, to an extent, bone cancer. In this review, we cover the current understanding of P2X7R regulation of bone cell formation, function and survival. We will discuss how the P2X7R drives lineage commitment of undifferentiated bone cell progenitors, the vital role of P2X7R activation in bone mineralisation and its relatively unexplored role in osteocyte function. We also review how P2X7R activation is imperative for osteoclast formation and its role in bone resorption via orchestrating osteoclast apoptosis. Variations in the gene for the P2X7R (P2RX7) have implications for P2X7R-mediated processes and we review the relevance of these genetic variations in bone physiology. Finally, we highlight how targeting P2X7R may have therapeutic potential in bone disease and cancer. PMID:25591582

  6. Long-term anabolic effects of prostaglandin-E2 on tibial diaphyseal bone in male rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1991-01-01

    The effects of long-term prostaglandin E2 (PGE2) on tibial diaphyseal bone were studied in 7-month-old male Sprague-Dawley rats given daily subcutaneous injections of 0, 1, 3 and 6 mg PGE2/kg/day for 60, 120 and 180 days. The tibial shaft was measured by single photon absorptiometry and dynamic histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial diaphyseal bone samples. Exogenous PGE2 administration produced the following transient changes in a dose-response manner between zero and 60 days: (1) increased bone width and mineral density; (2) increased total tissue and total bone areas; (3) decreased marrow area; (4) increased periosteal and corticoendosteal lamellar bone formation; (5) activated corticoendosteal lamellar and woven trabecular bone formation; and (6) activated intracortical bone remodeling. A new steady-state of increased tibial diaphyseal bone mass and elevated bone activities were observed from day 60 onward. The elevated bone mass level attained after 60 days of PGE2 treatment was maintained at 120 and 180 days. These observations indicate that the powerful anabolic effects of PGE2 will increase both periosteal and corticoendosteal bone mass and sustain the transient increase in bone mass with continuous daily administration of PGE2.

  7. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    SciTech Connect

    Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/?CT imaging. GSK-3 inhibitors caused ?-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/?CT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats.

  8. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    PubMed

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and ?SMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that ?SMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the ?SMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. PMID:26141839

  9. Effect of Royal Jelly on new bone formation in rapid maxillary expansion in rats

    PubMed Central

    Özan, Fatih; Çörekçi, Bayram; Halicio?lu, Koray; Irgin, Celal; Yilmaz, Fahri; Hezenci, Yasin

    2015-01-01

    Background The aim of this study was to evaluate the effects of long and short term systemic usage of royal jelly on bone formation in the expanded maxillary suture in a rat model. Material and Methods Twenty eight Wistar albino rats were randomly divided into 4 equal groups: Control (C); Only Expansion (OE), Royal Jelly (RJ) group, Royal Jelly was given to rats by oral gavage only during the expansion and retention period; Royal Jelly plus Nursery (RJN) group, Royal Jelly was given to rats by oral gavage during their nursery phase of 40 days and during the retention period. After the 5 day expansion period was completed, the rats underwent 12 days of mechanical retention. All rats were sacrificed in same time. Histological examination was performed to determine the number of osteoclasts, number of osteoblasts, number of capillaries, inflammatory cell infiltration, and new bone formation. Results New bone formation, number of osteoclasts, number of osteoblasts, and the number of capillaries in the expanded maxillary sutures were higher in the RJ and RJN groups than in the other groups. Statistical analysis also demonstrated that new bone formation and the number of osteoblasts was also highest in the RJN group. Conclusions The systemic administration of Royal Jelly in conjunction with rapid maxillary expansion may increase the quality of regenerated bone. Key words:Bone formation, rapid maxillary expansion, Royal jelly. PMID:26449428

  10. Extrinsic curvature, geometric optics, and lamellar order on curved substrates

    NASA Astrophysics Data System (ADS)

    Kamien, Randall D.; Nelson, David R.; Santangelo, Christian D.; Vitelli, Vincenzo

    2009-11-01

    When thermal energies are weak, two-dimensional lamellar structures confined on a curved substrate display complex patterns arising from the competition between layer bending and compression in the presence of geometric constraints. We present broad design principles to engineer the geometry of the underlying substrate so that a desired lamellar pattern can be obtained by self-assembly. Two distinct physical effects are identified as key factors that contribute to the interaction between the shape of the underlying surface and the resulting lamellar morphology. The first is a local ordering field for the direction of each individual layer, which tends to minimize its curvature with respect to the three-dimensional embedding. The second is a nonlocal effect controlled by the intrinsic geometry of the surface that forces the normals to the (nearly incompressible) layers to lie on geodesics, leading to caustic formation as in optics. As a result, different surface morphologies with predominantly positive or negative Gaussian curvature can act as converging or diverging lenses, respectively. By combining these ingredients, as one would with different optical elements, complex lamellar morphologies can be obtained. This smectic optometry enables the manipulation of lamellar configurations for the design of materials.

  11. Extrinsic Curvature, Geometric Optics, and Lamellar Order on Curved Substrates

    E-print Network

    R. D. Kamien; D. R. Nelson; C. D. Santangelo; V. Vitelli

    2009-08-29

    When thermal energies are weak, two dimensional lamellar structures confined on a curved substrate display complex patterns arising from the competition between layer bending and compression in the presence of geometric constraints. We present broad design principles to engineer the geometry of the underlying substrate so that a desired lamellar pattern can be obtained by self-assembly. Two distinct physical effects are identified as key factors that contribute to the interaction between the shape of the underlying surface and the resulting lamellar morphology. The first is a local ordering field for the direction of each individual layer which tends to minimize its curvature with respect to the three-dimensional embedding. The second is a non-local effect controlled by the intrinsic geometry of the surface that forces the normals to the (nearly incompressible) layers to lie on geodesics, leading to caustic formation as in optics. As a result, different surface morphologies with predominantly positive or negative Gaussian curvature can act as converging or diverging lenses respectively. By combining these ingredients, as one would with different optical elements, complex lamellar morphologies can be obtained. This smectic optometry enables the manipulation of lamellar configurations for the design of novel materials.

  12. Effect of coating Straumann Bone Ceramic with Emdogain on mesenchymal stromal cell hard tissue formation.

    PubMed

    Mrozik, Krzysztof Marek; Gronthos, Stan; Menicanin, Danijela; Marino, Victor; Bartold, P Mark

    2012-06-01

    Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional molecules. In this study, we investigated the capacity of Straumann Bone Ceramic coated with Straumann Emdogain, a clinical preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs) including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts (PDLFs). MSCs were isolated and ex vivo-expanded from human bone marrow and periodontal ligament and, in culture, allowed to attach to Bone Ceramic in the presence or absence of Emdogain. Gene expression of bone-related proteins was investigated by real time RT-PCR for 72 h, and ectopic bone formation was assessed histologically in subcutaneous implants of Bone Ceramic containing MSCs with or without Emdogain in NOD/SCID mice. Alkaline phosphatase activity was also assessed in vitro, in the presence or absence of Emdogain. Collagen-I mRNA was up-regulated in both MSC populations over the 72-h time course with Emdogain. Expression of BMP-2 and the osteogenic transcription factor Cbfa-1 showed early stimulation in both MSC types after 24 h. In contrast, expression of BMP-4 was consistently down-regulated in both MSC types with Emdogain. Up-regulation of osteopontin and periostin mRNA was restricted to BMSCs, while higher levels of bone sialoprotein-II were observed in PDLFs with Emdogain. Furthermore, alkaline phosphatase activity levels were reduced in both BMSCs and PDLFs in the presence of Emdogain. Very little evidence was found for ectopic bone formation following subcutaneous implantation of MSCs with Emdogain-coated or -uncoated Bone Ceramic in NOD/SCID mice. The early up-regulation of several important bone-related genes suggests that Emdogain may have a significant stimulatory effect in the commitment of mesenchymal cells to osteogenic differentiation in vitro. While Emdogain inhibited AP activity and appeared not to induce ectopic bone formation, longer-term studies are required to determine whether it promotes the final stages of osteoblast formation and mineralization at gene and protein levels. While used in clinical applications, whether Emdogain and other commercial preparations of EMPs truly possess the capacity to induce the regeneration of bone or other components of the periodontium remains to be established. PMID:21584694

  13. Estrogen receptor ? in osteocytes regulates trabecular bone formation in female mice

    PubMed Central

    Kondoh, Shino; Inoue, Kazuki; Igarashi, Katsuhide; Sugizaki, Hiroe; Shirode-Fukuda, Yuko; Inoue, Erina; Yu, Taiyong; Takeuchi, Jun K; Kanno, Jun; Bonewald, Lynda F; Imai, Yuuki

    2014-01-01

    Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, in which estrogen signaling may intersect with the Wnt/?-catenin pathway, is essential for bone maintenance. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER? deletion mice (ER??Ocy/?Ocy) were generated by mating ER? floxed mice with Dmp1-Cre mice to determine the role of ER? in osteocytes. Trabecular bone mineral density of female, but not male ER??Ocy/?Ocy mice was significantly decreased. Bone formation parameters in ER??Ocy/?Ocy were significantly decreased while osteoclast parameters were unchanged. This suggests that ER? in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ER?, gene array analysis of Dmp1-GFP osteocytes sorted by FACS from ER??Ocy/?Ocy and control mice was performed. Gene expression microarray followed by gene ontology analyses revealed that osteocytes from ER??Ocy/?Ocy highly expressed genes categorized in ‘Secreted’ when compared to control osteocytes. Among them, expression of Mdk and Sostdc1, both of which are Wnt inhibitors, was significantly increased without alteration of expression of the mature osteocyte marker Sost or ?-catenin. Moreover, hindlimb suspension experiments showed that trabecular bone loss due to unloading was greater in ER??Ocy/?Ocy mice with no loss of cortical bone. These data suggest that ER? in osteocytes has osteoprotective functions in trabecular bone formation through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading. PMID:24333171

  14. A computational analysis of bone formation in the cranial vault in the mouse.

    PubMed

    Lee, Chanyoung; Richtsmeier, Joan T; Kraft, Reuben H

    2015-01-01

    Bones of the cranial vault are formed by the differentiation of mesenchymal cells into osteoblasts on a surface that surrounds the brain, eventually forming mineralized bone. Signaling pathways causative for cell differentiation include the actions of extracellular proteins driven by information from genes. We assume that the interaction of cells and extracellular molecules, which are associated with cell differentiation, can be modeled using Turing's reaction-diffusion model, a mathematical model for pattern formation controlled by two interacting molecules (activator and inhibitor). In this study, we hypothesize that regions of high concentration of an activator develop into primary centers of ossification, the earliest sites of cranial vault bone. In addition to the Turing model, we use another diffusion equation to model a morphogen (potentially the same as the morphogen associated with formation of ossification centers) associated with bone growth. These mathematical models were solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data showing skull bone formation in mouse at different embryonic days in mice carrying disease causing mutations and their unaffected littermates. The results show that the relative locations of the five ossification centers that form in our model occur at the same position as those identified in experimental data. As bone grows from these ossification centers, sutures form between the bones. PMID:25853124

  15. A Computational Analysis of Bone Formation in the Cranial Vault in the Mouse

    PubMed Central

    Lee, Chanyoung; Richtsmeier, Joan T.; Kraft, Reuben H.

    2015-01-01

    Bones of the cranial vault are formed by the differentiation of mesenchymal cells into osteoblasts on a surface that surrounds the brain, eventually forming mineralized bone. Signaling pathways causative for cell differentiation include the actions of extracellular proteins driven by information from genes. We assume that the interaction of cells and extracellular molecules, which are associated with cell differentiation, can be modeled using Turing’s reaction–diffusion model, a mathematical model for pattern formation controlled by two interacting molecules (activator and inhibitor). In this study, we hypothesize that regions of high concentration of an activator develop into primary centers of ossification, the earliest sites of cranial vault bone. In addition to the Turing model, we use another diffusion equation to model a morphogen (potentially the same as the morphogen associated with formation of ossification centers) associated with bone growth. These mathematical models were solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data showing skull bone formation in mouse at different embryonic days in mice carrying disease causing mutations and their unaffected littermates. The results show that the relative locations of the five ossification centers that form in our model occur at the same position as those identified in experimental data. As bone grows from these ossification centers, sutures form between the bones. PMID:25853124

  16. Formation of hollow bone-like morphology of calcium carbonate on surfactant/polymer templates

    NASA Astrophysics Data System (ADS)

    Mantilaka, M. M. M. G. P. G.; Pitawala, H. M. T. G. A.; Rajapakse, R. M. G.; Karunaratne, D. G. G. P.; Upul Wijayantha, K. G.

    2014-04-01

    Novel hollow, bone-like structures of Precipitated Calcium Carbonate (PCC) are fabricated, for the first time, starting from naturally occurring dolomite. The hollow, bone-like structures are prepared by precipitating calcium carbonate on self-assembled poly(acrylic acid)/cetyltrimethylammonium chloride (PAA/CTAC) template. Fourier Transform Infrared Spectroscopy (FT-IR), X-ray diffraction (XRD), Transmission Electron Microscopy (TEM) and Field Emission Scanning Electron Microscopic (FE-SEM) studies reveal that the bone-like structure is composed of Amorphous Calcium Carbonate (ACC) nanoparticles in the center and calcite nanoparticles at the edges. Bone-like PCC particles are in particle length of 2-3 ?m and particle width of 1 ?m. The internal hollow structures of bone-like particles are observed from TEM images. As identified by FE-SEM images, the bone-like structure has been formed through the crystal growth of initially formed ACC nanoparticles. The ACC particles are stabilized in the center while the calcite crystals have been grown from the ACC toward the edges of the structure to form a bone-like morphology. We also propose a possible mechanism for the formation of hollow bone-like PCC in this study. The fabricated hollow, bone-like PCC has potential applications in the preparation of release systems such as drugs, cosmetics and pigments.

  17. Low-Level Mechanical Vibrations can Reduce Bone Resorption and Enhance Bone Formation in the Growing Skeleton

    SciTech Connect

    Xie,L.; Jacobsen, J.; Busa, B.; Donahue, L.; Miller, L.; Rubin, C.; Judex, S.

    2006-01-01

    Short durations of extremely small magnitude, high-frequency, mechanical stimuli can promote anabolic activity in the adult skeleton. Here, it is determined if such signals can influence trabecular and cortical formative and resorptive activity in the growing skeleton, if the newly formed bone is of high quality, and if the insertion of rest periods during the loading phase would enhance the efficacy of the mechanical regimen. Eight-week-old female BALB/cByJ mice were divided into four groups, baseline control (n = 8), age-matched control (n = 10), whole-body vibration (WBV) at 45 Hz (0.3 g) for 15 min day{sup -1} (n = 10), and WBV that were interrupted every second by 10 of rest (WBV-R, n = 10). In vivo strain gaging of two additional mice indicated that the mechanical signal induced strain oscillations of approximately 10 microstrain on the periosteal surface of the proximal tibia. After 3 weeks of WBV, applied for 15 min each day, osteoclastic activity in the trabecular metaphysis and epiphysis of the tibia was 33% and 31% lower (P < 0.05) than in age-matched controls. Bone formation rates (BFR{center_dot}BS{sup -1}) on the endocortical surface of the metaphysis were 30% greater (P < 0.05) in WBV than in age-matched control mice but trabecular and middiaphyseal BFR were not significantly altered. The insertion of rest periods (WBV-R) failed to potentiate the cellular effects. Three weeks of either WBV or WBV-R did not negatively influence body mass, bone length, or chemical bone matrix properties of the tibia. These data indicate that in the growing skeleton, short daily periods of extremely small, high-frequency mechanical signals can inhibit trabecular bone resorption, site specifically attenuate the declining levels of bone formation, and maintain a high level of matrix quality. If WBV prove to be efficacious in the growing human skeleton, they may be able to provide the basis for a non-pharmacological and safe means to increase peak bone mass and, ultimately, reduce the incidence of osteoporosis or stress fractures later in life.

  18. Permian Bone Spring formation: Sandstone play in the Delaware basin. Part I - slope

    SciTech Connect

    Montgomery, S.L.

    1997-08-01

    New exploration in the Permian (Leonardian) Bone Spring formation has indicated regional potential in several sandstone sections across portions of the northern Delaware basin. Significant production has been established in the first, second, and third Bone Spring sandstones, as well as in a new reservoir interval, the Avalon sandstone, above the first Bone Spring sandstone. These sandstones were deposited as submarine-fan systems within the northern Delaware basin during periods of lowered sea level. The Bone Spring as a whole consists of alternating carbonate and siliciclastic intervals representing the downdip equivalents to thick Abo-Yeso/Wichita-Clear Fork carbonate buildups along the Leonardian shelf margin. Hydrocarbon exploration in the Bone Spring has traditionally focused on debris-flow carbonate deposits restricted to the paleoslope. Submarine-fan systems, in contrast, extend a considerable distance basinward of these deposits and have been recently proven productive as much as 40-48 km south of the carbonate trend.

  19. Geochemical and mineralogical studies of dinosaur bone from the Morrison Formation at Dinosaur Ridge

    USGS Publications Warehouse

    Modreski, P.J.

    2001-01-01

    The dinosaur bones first discovered in 1877 in the Upper Jurassic Morrison Formation at Morrison, Colorado were the first major find of dinosaur skeletons in the western U.S. and led to the recognition of four new dinosaur genera (Apatosaurus, Allosaurus, Diplodocus, and Stegosaurus). Eight articles dealing with these bones which appeared as research reports in the annual reports of the Friends of Dinosaur Ridge from 1990-1999 are condensed and summarized with some additional comments. Two of the articles are about the mineralogy and preservation of the bones; two are about the physical description of the bone occurrence; two are about the history of the site, and two are about use of novel instrumental methods (ground-penetrating radar and a directional scintillometer) to search for new bones.

  20. Analyses Using Micro-CT Scans and Tissue Staining on New Bone Formation and Bone Fusion According to the Timing of Cranioplasty via Frozen Autologous Bone Flaps in Rabbits : A Preliminary Report

    PubMed Central

    Shin, Hee Sup; Lee, Deok-Won; Koh, Jun Seok

    2015-01-01

    Objective The timing of cranioplasty and method of bone flap storage are known risk factors of non-union and resorption of bone flaps. In this animal experimental study, we evaluated the efficacy of cranioplasty using frozen autologous bone flap, and examined whether the timing of cranioplasty after craniectomy affects bone fusion and new bone formation. Methods Total 8 rabbits (male, older than 16 weeks) were divided into two groups of early cranioplasty group (EG, 4 rabbits) and delayed cranioplasty group (DG, 4 rabbits). The rabbits of each group were performed cranioplasty via frozen autologous bone flaps 4 weeks (EG) and 8 weeks (DG) after craniectomy. In order to obtain control data, the cranioplasty immediate after craniectomy were made on the contralateral cranial bone of the rabbits (control group, CG).The bone fusion and new bone formation were evaluated by micro-CT scan and histological examination 8 weeks after cranioplasty on both groups. Results In the micro-CT scans, the mean values of the volume and the surface of new bone were 50.13±7.18 mm3 and 706.23±77.26 mm2 in EG, 53.78±10.86 mm3 and 726.60±170.99 mm2 in DG, and 31.51±12.84 mm3 and 436.65±132.24 mm2 in CG. In the statistical results, significant differences were shown between EG and CG and between DG and CG (volume : p=0.028 and surface : p=0.008). The histological results confirmed new bone formation in all rabbits. Conclusion We observed new bone formation on all the frozen autologous bone flaps that was stored within 8 weeks. The timing of cranioplasty may showed no difference of degree of new bone formation. Not only the healing period after cranioplasty but the time interval from craniectomy to cranioplasty could affect the new bone formation. PMID:25932290

  1. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    PubMed Central

    Tatl?, Ali Murat; Göksu, Sema Sezgin; Arslan, Deniz; Ba?sorgun, Cumhur ?brahim; Co?kun, Hasan ?enol

    2013-01-01

    Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage. PMID:23956898

  2. [Anti-sclerostin antibody : its bone formation effect and therapeutic potential for osteoporosis].

    PubMed

    Endo, Itsuro

    2014-01-01

    In a rare accident of nature, some families have been found to have dense and strong bones due to a recessive loss of function mutation in the SOST gene that encodes for sclerostin, a protein expressed by osteocytes that downregulates osteoblastic bone formation. Knowledge of this molecule and its actions led rather quickly to the development of anti-sclerostin antibodies that lead to marked increases in bone mass in both animals and human subjects. Blocking sclerostin action with anti-sclerostin antibodies is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis. PMID:24369282

  3. Osseous metaplasia with formation of hematopoietic bone marrow in a blind, painful eye.

    PubMed

    Manusow, Joshua S; Brownstein, Seymour; Jordan, David R

    2011-01-01

    A 31-year-old woman underwent an evisceration of her blind, painful right eye with placement of an aluminum oxide orbital implant. Histopathologic assessment revealed functional hematopoietic bone marrow, confirmed by immunohistochemistry, within osseous metaplasia of the retinal pigment epithelium. This finding is exceedingly rare, with few cases reported in the English literature. This report raises numerous questions, including the association between pain and hematopoietic bone marrow formation, the potential benefits of hematopoietic bone marrow in the eye, and the molecular biologic basis for this rare phenomenon. PMID:20924302

  4. WNT7B Promotes Bone Formation in part through mTORC1

    PubMed Central

    Chen, Jianquan; Tu, Xiaolin; Esen, Emel; Joeng, Kyu Sang; Lin, Congxin; Arbeit, Jeffrey M.; Rüegg, Markus A.; Hall, Michael N.; Ma, Liang; Long, Fanxin

    2014-01-01

    WNT signaling has been implicated in both embryonic and postnatal bone formation. However, the pertinent WNT ligands and their downstream signaling mechanisms are not well understood. To investigate the osteogenic capacity of WNT7B and WNT5A, both normally expressed in the developing bone, we engineered mouse strains to express either protein in a Cre-dependent manner. Targeted induction of WNT7B, but not WNT5A, in the osteoblast lineage dramatically enhanced bone mass due to increased osteoblast number and activity; this phenotype began in the late-stage embryo and intensified postnatally. Similarly, postnatal induction of WNT7B in Runx2-lineage cells greatly stimulated bone formation. WNT7B activated mTORC1 through PI3K-AKT signaling. Genetic disruption of mTORC1 signaling by deleting Raptor in the osteoblast lineage alleviated the WNT7B-induced high-bone-mass phenotype. Thus, WNT7B promotes bone formation in part through mTORC1 activation. PMID:24497849

  5. Vascularized Bone Tissue Formation Induced by Fiber-Reinforced Scaffolds Cultured with Osteoblasts and Endothelial Cells

    PubMed Central

    Liu, Xinhui; Zhang, Guoping; Hou, Chuanyong; Wang, Hua; Yang, Yelin; Guan, Guoping; Dong, Wei; Gao, Hongyang

    2013-01-01

    The repair of the damaged bone tissue caused by damage or bone disease was still a problem. Current strategies including the use of autografts and allografts have the disadvantages, namely, diseases transmission, tissue availability and donor morbidity. Bone tissue engineering has been developed and regarded as a new way of regenerating bone tissues to repair or substitute damaged or diseased ones. The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system, the vascularization. In this paper, a new-typed hydroxyapatite/collagen composite scaffold which was reinforced by chitosan fibers and cultured with osteoblasts and endothelial cells was fabricated. General observation, histological observation, detection of the degree of vascularization, and X-ray examination had been done to learn the effect of vascularized bone repair materials on the regeneration of bone. The results show that new vessel and bone formed using implant cultured with osteoblasts and endothelial cells. Nanofiber-reinforced scaffold cultured with osteoblasts and endothelial cells can induce vascularized bone tissue formation. PMID:24369019

  6. Adsorption of dimeric surfactants in lamellar silicates

    NASA Astrophysics Data System (ADS)

    Balcerzak, Mateusz; Pietralik, Zuzanna; Domka, Ludwik; Skrzypczak, Andrzej; Kozak, Maciej

    2015-12-01

    The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay - hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1?-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d001) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH2 and CH3 groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

  7. Creep of fully lamellar near {gamma}-TiAl intermetallics

    SciTech Connect

    Beddoes, J.; Zhao, L.; Chen, W.R.; Du, X.

    1999-07-01

    The influence of the fully lamellar morphology and third phase {beta} on the creep properties of near {gamma}-TiAl intermetallics is presented. Specifically, the effect of improved microstructural control obtainable by a stepped cool, involving furnace cooling and air cooling from the {alpha} single phase, on creep resistance is demonstrated for three near {gamma}-TiAl intermetallics: binary Ti-48Al, ternary Ti-48Al-2W and Ti-47Al-2Nb-1Mn-0.5W-0.5Mo-0.2Si. The results indicate that appropriate stepped cooling can be used to reduce the lamellar interface spacing without the formation of Widmanstaetten, feathery {gamma} or {gamma}{sub M} structures, leading to longer creep life and reduced creep strain rates. A second benefit of stepped cooling is prevention of {beta} formation during cooling from the {alpha} phase, allowing controlled {beta} precipitation during aging at 950 C. Creep tests on variously aged Ti-48Al-2W indicate that {beta} precipitation along lamellar grain boundaries improves creep resistance. Development of a uniform fully lamellar structure in Ti-47Al-2Nb-1Mn-0.5W-0.5Mo-0.2Si significantly improves creep resistance. Applying the stepped cool to this alloy allows the precipitation of {beta} and silicides to be controlled during lower temperature aging.

  8. Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption.

    PubMed

    Razi, Hajar; Birkhold, Annette I; Weinkamer, Richard; Duda, Georg N; Willie, Bettina M; Checa, Sara

    2015-10-01

    Physical activity is essential to maintain skeletal mass and structure, but its effect seems to diminish with age. To test the hypothesis that bone becomes less sensitive to mechanical strain with age, we used a combined in vivo/in silico approach. We investigated how maturation and aging influence the mechanical regulation of bone formation and resorption to 2 weeks of noninvasive in vivo controlled loading in mice. Using 3D in vivo morphometrical assessment of longitudinal microcomputed tomography images, we quantified sites in the mouse tibia where bone was deposited or resorbed in response to controlled in vivo loading. We compared the (re)modeling events (formation/resorption/quiescent) to the mechanical strains induced at these sites (predicted using finite element analysis). Mice of all age groups (young, adult, and elderly) responded to loading with increased formation and decreased resorption, preferentially at high strains. Low strains were associated with no anabolic response in adult and elderly mice, whereas young animals showed a strong response. Adult animals showed a clear separation between strain ranges where formation and resorption occurred but without an intermediate quiescent "lazy zone". This strain threshold disappeared in elderly mice, as mechanically induced (re)modeling became dysregulated, apparent in an inability to inhibit resorption or initiate formation. Contrary to what is generally believed until now, aging does not shift the mechanical threshold required to initiate formation or resorption, but rather blurs its specificity. These data suggest that pharmaceutical strategies augmenting physical exercise should consider this dysfunction in the mechanical regulation of bone (re)modeling to more effectively combat age-related bone loss. © 2015 American Society for Bone and Mineral Research. PMID:25857303

  9. Effects of designed PLLA and 50:50PLGA scaffold architectures on bone formation in vivo

    PubMed Central

    Saito, Eiji; Liao, Elly E.; Hu, Wei-Wen; Krebsbach, Paul H.; Hollister, Scott J.

    2015-01-01

    Biodegradable porous scaffolds have been investigated as an alternative approach to current metal, ceramic, and polymer bone graft substitutes for lost or damaged bone tissues. Although there have been many studies investigating the effects of scaffold architecture on bone formation, many of these scaffolds were fabricated using conventional methods, such as salt leaching and phase separation, and were constructed without designed architecture. To study the effects of both designed architecture and material on bone formation, we designed and fabricated three types of porous scaffold architecture from two biodegradable materials, poly (L-lactic acid) (PLLA) and 50:50Poly (lactic-co-glycolic acid) (PLGA) using image based design and indirect solid freeform fabrication techniques, seeded them with bone morphogenic protein-7 transduced human gingival fibroblasts and implanted them subcutaneously into mice for 4 and 8 weeks. Micro-computed tomography data confirmed that the fabricated porous scaffolds replicated the designed architectures. Histological analysis revealed that the 50:50PLGA scaffolds degraded and did not maintain their architecture after 4 weeks. The PLLA scaffolds maintained their architecture at both time points and showed improved bone ingrowth which followed the internal architecture of the scaffolds. Mechanical properties of both PLLA and 50:50PLGA scaffolds decreased, but PLLA scaffolds maintained greater mechanical properties than 50:50PLGA after implantation. The increase of mineralized tissue helped to support mechanical properties of bone tissue and scaffold constructs from 4 to 8 weeks. The results indicated the importance of choice of scaffold materials and computationally designed scaffolds to control tissue formation and mechanical properties for desired bone tissue regeneration. PMID:22162220

  10. Soluble and insoluble signals and the induction of bone formation: molecular therapeutics recapitulating development

    PubMed Central

    Ripamonti, Ugo; Ferretti, C; Heliotis, M

    2006-01-01

    The osteogenic molecular signals of the transforming growth factor-? (TGF-?) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs) and uniquely in primates the TGF-? isoforms per se, pleiotropic members of the TGF-? supergene family, induce de novo endochondral bone formation as a recapitulation of embryonic development. Naturally derived BMPs/OPs and gamma-irradiated human recombinant osteogenic protein-1 (hOP-1) delivered by allogeneic and xenogeneic insoluble collagenous matrices initiate de novo bone induction in heterotopic and orthotopic sites of the primate Papio ursinus, culminating in complete calvarial regeneration by day 90 and maintaining the regenerated structures by day 365. The induction of bone by hOP-1 in P. ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF-? superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. The temporal and spatial expressions of TGF-?1 mRNA indicate a specific temporal transcriptional window during which expression of TGF-?1 is mandatory for successful and optimal osteogenesis. Highly purified naturally derived bovine BMPs/OPs and hOP-1 delivered by human collagenous bone matrices and porous hydroxyapatite, respectively, induce bone formation in mandibular defects of human patients. By using healthy body sites as bioreactors it is possible to recapitulate embryonic developments by inducing selected biomaterials combined with recombinant proteins to transform into custom-made prefabricated bone grafts for human reconstruction. The osteogenic proteins of the TGF-? superfamily, BMPs/OPs and TGF-?s, the last endowed with the striking prerogative of inducing endochondral bone formation in primates only, are helping to engineer skeletal reconstruction in molecular terms. PMID:17005018

  11. An activating Fgfr3 mutation affects trabecular bone formation via a paracrine mechanism during growth.

    PubMed

    Mugniery, Emilie; Dacquin, Romain; Marty, Caroline; Benoist-Lasselin, Catherine; de Vernejoul, Marie-Christine; Jurdic, Pierre; Munnich, Arnold; Geoffroy, Valérie; Legeai-Mallet, Laurence

    2012-06-01

    The fibroblast growth factor receptor 3 (FGFR3) plays a critical role in the regulation of endochondral ossification. Fgfr3 gain-of-function mutations cause achondroplasia, the most common form of dwarfism, and a spectrum of chondrodysplasias. Despite a significant number of studies on the role of FGFR3 in cartilage, to date, none has investigated the influence of Fgfr3-mediated effects of the growth plate on bone formation. We studied three mouse models, each expressing Fgfr3 mutation either ubiquitously (CMV-Fgfr3(Y367C/+)), in chondrocytes (Col II-Fgfr3(Y367C/+)) or in mature osteoblasts (Col I-Fgfr3(Y367C/+)). Interestingly, we demonstrated that dwarfism with a significant defect in bone formation during growth was only observed in mouse models expressing mutant Fgfr3 in the cartilage. We observed a dramatic reduction in cartilage matrix mineralization and a strong defect of primary spongiosa. Anomalies of primary spongiosa were associated with an increase in osteoclast recruitment and a defect of osteoblasts at the mineralization front. A significant decrease in bone volume, trabecular thickness and number was also observed in the trabecular bone. Interestingly, no anomalies in proliferation and differentiation of primary osteoblasts from CMV-Fgfr3(Y367C/+) mice were observed. Based on these data, we excluded a potential function of Fgfr3 directly on osteoblasts at 3 weeks of age and we obtained evidence that the disorganization of the growth plate is responsible for the anomalies of the trabecular bone during bone formation. Herein, we propose that impaired FGFR3 signaling pathways may affect trabecular bone formation via a paracrine mechanism during growth. These results redefine our understanding of endochondral ossification in FGFR3-related chondrodysplasias. PMID:22367969

  12. In vivo bone formation by progeny of human embryonic stem cells.

    PubMed

    Kuznetsov, Sergei A; Cherman, Natasha; Robey, Pamela Gehron

    2011-02-01

    The derivation of osteogenic cells from human embryonic stem cells (hESCs) or from induced pluripotent stem cells for bone regeneration would be a welcome alternative to the use of adult stem cells. In an attempt to promote hESC osteogenic differentiation, cells of the HSF-6 line were cultured in differentiating conditions in vitro for prolonged periods of time ranging from 7 to 14.5 weeks, followed by in vivo transplantation into immunocompromised mice in conjunction with hydroxyapatite/tricalcium phosphate ceramic powder. Twelve different medium compositions were tested, along with a number of other variables in culture parameters. In differentiating conditions, HSF-6-derived cells demonstrated an array of diverse phenotypes reminiscent of multiple tissues, but after a few passages, acquired a more uniform, fibroblast-like morphology. Eight to 16 weeks post-transplantation, a group of transplants revealed the formation of histologically proven bone of human origin, including broad areas of multiple intertwining trabeculae, which represents by far the most extensive in vivo bone formation by the hESC-derived cells described to date. Knockout-Dulbecco's modified Eagle's medium-based media with fetal bovine serum, dexamethasone, and ascorbate promoted more frequent bone formation, while media based on ?-modified minimum essential medium promoted teratoma formation in 12- to 20-week-old transplants. Transcription levels of pluripotency-related (octamer binding protein 4, Nanog), osteogenesis-related (collagen type I, Runx2, alkaline phosphatase, and bone sialoprotein), and chondrogenesis-related (collagen types II and X, and aggrecan) genes were not predictive of either bone or teratoma formation. The most extensive bone was formed by the strains that, following 4 passages in monolayer conditions, were cultured for 23 to 25 extra days on the surface of hydroxyapatite/tricalcium phosphate particles, suggesting that coculturing of hESC-derived cells with osteoconductive material may increase their osteogenic potential. While none of the conditions tested in this study, and elsewhere, ensured consistent bone formation by hESC-derived cells, our results may elucidate further directions toward the construction of bone on the basis of hESCs or an individual's own induced pluripotent stem cells. PMID:20590404

  13. Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

    PubMed Central

    Cheng, Tegan L; Murphy, Ciara M; Ravarian, Roya; Dehghani, Fariba; Little, David G; Schindeler, Aaron

    2015-01-01

    Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. 14C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA?>?micro-HA?>?TCP?>?BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA–adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA–adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering. PMID:26668709

  14. Nanoscale confinement controls the crystallization of calcium phosphate: relevance to bone formation.

    PubMed

    Cantaert, Bram; Beniash, Elia; Meldrum, Fiona C

    2013-10-25

    A key feature of biomineralization processes is that they take place within confined volumes, in which the local environment can have significant effects on mineral formation. Herein, we investigate the influence of confinement on the formation mechanism and structure of calcium phosphate (CaP). This is of particular relevance to the formation of dentine and bone, structures of which are based on highly mineralized collagen fibrils. CaP was precipitated within 25-300?nm diameter, cylindrical pores of track etched and anodised alumina membranes under physiological conditions, in which this system enables systematic study of the effects of the pore size in the absence of a structural match between the matrix and the growing crystals. Our results show that the main products were polycrystalline hydroxapatite (HAP) rods, together with some single crystal octacalcium phosphate (OCP) rods. Notably, we demonstrate that these were generated though an intermediate amorphous calcium phosphate (ACP) phase, and that ACP is significantly stabilised in confinement. This effect may have significance to the mineralization of bone, which can occur through a transient ACP phase. We also show that orientation of the HAP comparable, or even superior to that seen in bone can be achieved through confinement effects alone. Although this simple experimental system cannot be considered, a direct mimic of the in vivo formation of ultrathin HAP platelets within collagen fibrils, our results show that the effects of physical confinement should not be neglected when considering the mechanisms of formation of structures, such as bones and teeth. PMID:24115275

  15. The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

    NASA Technical Reports Server (NTRS)

    Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

    1985-01-01

    The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

  16. Determination of the Fate and Contribution of Ex Vivo Expanded Human Bone Marrow Stem and Progenitor Cells for Bone Formation by 2.3ColGFP

    PubMed Central

    Yin, Dezhong; Wang, Zhuo; Gao, Qinghong; Sundaresan, Renuka; Parrish, Chris; Yang, Qingfen; Krebsbach, Paul H; Lichtler, Alexander C; Rowe, David W; Hock, Janet; Liu, Peng

    2009-01-01

    Bone marrow transplantation can provide an effective cell-based strategy to enhance bone repair. However, the fate of implanted cells and the extent of their contribution to bone osteoinduction remain uncertain. To define the fate of bone marrow–derived cells and their contribution in vivo, we used a bone-specific collagen I promoter (2.3Col) driving green fluorescent protein (GFP) (2.3ColGFP) within a lentiviral vector. Prior to in vivo cell fate determination, we verified a high efficiency of lentiviral transduction in human bone marrow stromal cells (hBMSCs), without altering the proliferation or differentiation potential of these cells. We showed that the 2.3ColGFP marker responded to endogenous transcriptional regulation signals. In a mouse ossicle model, we demonstrated that the 2.3ColGFP marker is able to specifically define human bone marrow–derived stem cells that enter the osteoblast lineage in vivo. In addition, cells labeled with 2.3ColGFP with the donor origin, directly make a major contribution to bone formation. Furthermore, we also demonstrated in a calvarial defect model that a mixture of human bone marrow–derived populations, have stronger bone regenerative potential than that of hBMSCs, and an optimal dose is required for bone regeneration by the mixed populations. PMID:19603005

  17. Instability mechanisms in lamellar microstructures

    SciTech Connect

    Sharma, G.; Ramanujan, R.V.; Tiwari, G.P.

    2000-02-25

    The shape instabilities associated with a lamellar structure when exposed to elevated temperature have been analyzed. These instabilities were compared with experimental data from Ti-47Al, Ti-47Al-140 a.p.p.m. B and Ti-47Al-0.5 at.% W-140 a.p.p.m. B alloys. Instability maps, which were constructed for an isolated plate, show that the dominant mechanism controlling the coarsening of lamellae changes with time and also show that coarsening of lamellae with an initially large aspect ratio is controlled by termination migration, until the aspect ratio falls to some critical value below which cylinderization becomes the dominant mechanism. Instability maps were also constructed using the criterion of maximum mass transport rate per unit volume. Such volume instability maps show that the coarsening rate associated with a unit volume of the lamellar structure depends on the density of faults and that termination migration and boundary splitting occurs at a considerable rate as compared with other continuous coarsening mechanisms. The effect of alloying additions of B and W to the Ti-47Al alloy was to reduce the coarsening rate of the initial lamellar structure.

  18. The effect of the microenvironment created by a titanium mesh cage on subcutaneous experimental bone formation and inhibition of absorption.

    PubMed

    Tanoue, Ryuichiro; Ohta, Keisuke; Kusukawa, Jingo; Nakamura, Kei-ichiro

    2012-01-01

    We attempted to form ectopic bone under the skin of rats without adding any extrinsic bone-inducing growth factors or cytokines using bone marrow stromal cells (BMSCs), a collagen scaffold and a titanium mesh cage. We set up a space made up of a cage inserted into the subcutaneous region of rats' backs, where we could eliminate the possible influence of residual bone tissue on bone induction. We filled this space with a collagen matrix containing BMSCs. At week 8 and month 6 after implantation, the specimens were removed and observed histologically, histochemically and enzyme histochemically. As a result, bone tissue was identified in each case within the titanium cages, even though we had not used bone-inducing chemical substances. Bone generation was not found in test cases without a cage. Enhanced green fluorescence protein (EGFP) labeling of the implanted BMSCs clearly showed that these cells differentiated into osteoblasts and subsequently into osteocytes in the formed bone tissue. Host cells without EGFP labeling were also confirmed to be involved in bone formation. Six months after transplantation, the implanted cells were still present in the generated bone, and no significant resorption of the generated bone was observed. These results indicate that the physically stable spatial microenvironment created by the cage in vivo plays an important role in bone formation and inhibition of its resorption, which we refer to as the 'cage effect'. PMID:22538638

  19. Disruption of Kif3a in osteoblasts results in defective bone formation and osteopenia

    PubMed Central

    Qiu, Ni; Xiao, Zhousheng; Cao, Li; Buechel, Meagan M.; David, Valentin; Roan, Esra; Quarles, L. Darryl

    2012-01-01

    We investigated whether Kif3a in osteoblasts has a direct role in regulating postnatal bone formation. We conditionally deleted Kif3a in osteoblasts by crossing osteocalcin (Oc; also known as Bglap)–Cre with Kif3aflox/null mice. Conditional Kif3a-null mice (Kif3aOc-cKO) had a 75% reduction in Kif3a transcripts in bone and osteoblasts. Conditional deletion of Kif3a resulted in the reduction of primary cilia number by 51% and length by 27% in osteoblasts. Kif3aOc-cKO mice developed osteopenia by 6 weeks of age unlike Kif3aflox/+ control mice, as evidenced by reductions in femoral bone mineral density (22%), trabecular bone volume (42%) and cortical thickness (17%). By contrast, Oc-Cre;Kif3aflox/+ and Kif3aflox/null heterozygous mice exhibited no skeletal abnormalities. Loss of bone mass in Kif3aOc-cKO mice was associated with impaired osteoblast function in vivo, as reflected by a 54% reduction in mineral apposition rate and decreased expression of Runx2, osterix (also known as Sp7 transcription factor 7; Sp7), osteocalcin and Dmp1 compared with controls. Immortalized osteoblasts from Kif3aOc-cKO mice exhibited increased cell proliferation, impaired osteoblastic differentiation, and enhanced adipogenesis in vitro. Osteoblasts derived from Kif3aOc-cKO mice also had lower basal cytosolic calcium levels and impaired intracellular calcium responses to fluid flow shear stress. Sonic hedgehog-mediated Gli2 expression and Wnt3a-mediated ?-catenin and Axin2 expression were also attenuated in Kif3aOc-cKO bone and osteoblast cultures. These data indicate that selective deletion of Kif3a in osteoblasts disrupts primary cilia formation and/or function and impairs osteoblast-mediated bone formation through multiple pathways including intracellular calcium, hedgehog and Wnt signaling. PMID:22357948

  20. 3D analysis of bone formation around titanium implants using micro-computed tomography (?CT)

    NASA Astrophysics Data System (ADS)

    Bernhardt, Ricardo; Scharnweber, Dieter; Müller, Bert; Beckmann, Felix; Goebbels, Jürgen; Jansen, John; Schliephake, Henning; Worch, Hartmut

    2006-08-01

    The quantitative analysis of bone formation around biofunctionalised metallic implants is an important tool for the further development of implants with higher success rates. This is, nowadays, especially important in cases of additional diseases like diabetes or osteoporosis. Micro computed tomography (?CT), as non-destructive technique, offers the possibility for quantitative three-dimensional recording of bone close to the implant's surface with micrometer resolution, which is the range of the relevant bony structures. Within different animal models using cylindrical and screw-shaped Ti6Al4V implants we have compared visualization and quantitative analysis of newly formed bone by the use of synchrotron-radiation-based CT-systems in comparison with histological findings. The SR?CT experiments were performed at the beamline BW 5 (HASYLAB at DESY, Hamburg, Germany; at the BAMline (BESSY, Berlin, Germany). For the experiments, PMMA-embedded samples were prepared with diameters of about 8 mm, which contain in the center the implant surrounded by the bony tissue. To (locally) quantify the bone formation, models were developed and optimized. The comparison of the results obtained by SR?CT and histology demonstrates the advantages and disadvantages of both approaches, although the bone formation values for the different biofunctionalized implants are identical within the error bars. SR?CT allows the clear identification of fully mineralized bone around the different titanium implants. As hundreds of virtual slices were easily generated for the individual samples, the quantification and interactive bone detection led to conclusions of high precision and statistical relevance. In this way, SR?CT in combination with interactive data analysis is proven to be more significant with respect to classical histology.

  1. INSECT TRACE FOSSILS ON DINOSAUR BONES FROM THE UPPER JURASSIC MORRISON FORMATION, NORTHEASTERN WYOMING, AND THEIR USE IN VERTEBRATE TAPHONOMY

    E-print Network

    Bader, Kenneth Stephen

    2008-08-21

    ON DINOSAUR BONES FROM THE UPPER JURASSIC MORRISON FORMATION, NORTHEASTERN WYOMING, AND THEIR USE IN VERTEBRATE TAPHONOMY by ? 2008 Kenneth Stephen Bader B.S., University of Kansas, 2003 Submitted to the Department of Geology and the Faculty... of the following thesis: INSECT TRACE FOSSILS ON DINOSAUR BONES FROM THE UPPER JURASSIC MORRISON FORMATION, NORTHEASTERN WYOMING, AND THEIR USE IN VERTEBRATE TAPHONOMY Advisory Committee...

  2. Cellular and morphological aspects of fibrodysplasia ossificans progressiva. Lessons of formation, repair, and bone bioengineering.

    PubMed

    Martelli, Anderson; Santos, Arnaldo Rodrigues

    2014-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease that causes bone formation within the muscles, tendons, ligaments and connective tissues. There is no cure for this disorder and only treatment of the symptoms is available. The purpose of this study was to review the literature and describe the clinical, cellular and molecular aspects of FOP. The material used for the study was obtained by reviewing scientific articles published in various literature-indexed databases. In view of its rarity and of the lack of insightful information and the unpredictability of its course, FOP is a challenging disorder for professionals who are confronted by it. However, this rare disease raises a great deal of interest because understanding the mechanism of mature bone formation can encourage research lines related to bone regeneration and the prevention of heterotopic ossification. PMID:25482313

  3. Non-lamellar lipid liquid crystalline structures at interfaces.

    PubMed

    Chang, Debby P; Barauskas, Justas; Dabkowska, Aleksandra P; Wadsäter, Maria; Tiberg, Fredrik; Nylander, Tommy

    2015-08-01

    The self-assembly of lipids leads to the formation of a rich variety of nano-structures, not only restricted to lipid bilayers, but also encompassing non-lamellar liquid crystalline structures, such as cubic, hexagonal, and sponge phases. These non-lamellar phases have been increasingly recognized as important for living systems, both in terms of providing compartmentalization and as regulators of biological activity. Consequently, they are of great interest for their potential as delivery systems in pharmaceutical, food and cosmetic applications. The compartmentalizing nature of these phases features mono- or bicontinuous networks of both hydrophilic and hydrophobic domains. To utilize these non-lamellar liquid crystalline structures in biomedical devices for analyses and drug delivery, it is crucial to understand how they interact with and respond to different types of interfaces. Such non-lamellar interfacial layers can be used to entrap functional biomolecules that respond to lipid curvature as well as the confinement. It is also important to understand the structural changes of deposited lipid in relation to the corresponding bulk dispersions. They can be controlled by changing the lipid composition or by introducing components that can alter the curvature or by deposition on nano-structured surface, e.g. vertical nano-wire arrays. Progress in the area of liquid crystalline lipid based nanoparticles opens up new possibilities for the preparation of well-defined surface films with well-defined nano-structures. This review will focus on recent progress in the formation of non-lamellar dispersions and their interfacial properties at the solid/liquid and biologically relevant interfaces. PMID:25435157

  4. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development

    PubMed Central

    Ducy, Patricia; Starbuck, Michael; Priemel, Matthias; Shen, Jianhe; Pinero, Gerald; Geoffroy, Valerie; Amling, Michael; Karsenty, Gerard

    1999-01-01

    The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in Cbfa1-deficient mice has prevented so far the study of its function after birth. To determine if Cbfa1 plays a role during bone formation we generated transgenic mice overexpressing Cbfa1 DNA-binding domain (?Cbfa1) in differentiated osteoblasts only postnatally. ?Cbfa1 has a higher affinity for DNA than Cbfa1 itself, has no transcriptional activity on its own, and can act in a dominant-negative manner in DNA cotransfection assays. ?Cbfa1-expressing mice have a normal skeleton at birth but develop an osteopenic phenotype thereafter. Dynamic histomorphometric studies show that this phenotype is caused by a major decrease in the bone formation rate in the face of a normal number of osteoblasts thus indicating that once osteoblasts are differentiated Cbfa1 regulates their function. Molecular analyses reveal that the expression of the genes expressed in osteoblasts and encoding bone ECM proteins is nearly abolished in transgenic mice, and ex vivo assays demonstrated that ?Cbfa1-expressing osteoblasts were less active than wild-type osteoblasts. We also show that Cbfa1 regulates positively the activity of its own promoter, which has the highest affinity Cbfa1-binding sites characterized. This study demonstrates that beyond its differentiation function Cbfa1 is the first transcriptional activator of bone formation identified to date and illustrates that developmentally important genes control physiological processes postnatally. PMID:10215629

  5. Lymphangiosarcoma with bone formation of the auricle in a dog

    PubMed Central

    MINESHIGE, Takayuki; SUGAHARA, Go; OHMURO, Tamio; KAMIIE, Junichi; SHIROTA, Kinji

    2015-01-01

    A 12-year-old mixed-breed neutered female dog was referred with cutaneous tumors at the left auricle. Histologically, the cutaneous tumor located in the dermis comprised numerous clefts and cavernous channels lined by neoplastic endothelial cells with no erythrocytes. Bone tissue without direct contact with neoplastic cells was seen in the well-developed stromal connective tissue. The neoplastic endothelial cells exhibited mild to moderate atypia. Immunohistochemically, neoplastic cells were positive for vimentin and negative for cytokeratin and factor VIII-related antigen. Basement membrane around the neoplastic lumens was positive for laminin in a linear or granular pattern. Ultrastructural examination revealed discontinuous basement membrane beneath the tumor cells. Histopathological features of this case were consistent with lymphangiosarcoma, and stromal ossification was characteristic. PMID:25716121

  6. Chondrocytes-Specific Expression of Osteoprotegerin Modulates Osteoclast Formation in Metaphyseal Bone

    PubMed Central

    Wang, Baoli; Jin, Hongting; Shu, Bing; Mira, Ranim R.; Chen, Di

    2015-01-01

    Bone marrow stromal cells/osteoblasts were originally thought to be the major player in regulating osteoclast differentiation through expressing RANKL/OPG cytokines. Recent studies have established that chondrocytes also express RANKL/OPG and support osteoclast formation. Till now, the in vivo function of chondrocyte-produced OPG in osteoclast formation and postnatal bone growth has not been directly investigated. In this study, chondrocyte-specific Opg transgenic mice were generated by using type II collagen promoter. The Col2-Opg transgenic mice showed delayed formation of secondary ossification center and localized increase of bone mass in proximal metaphysis of tibiae. TRAP staining showed that osteoclast numbers were reduced in both secondary ossification center and proximal metaphysis. This finding was further confirmed by in vitro chondrocyte/spleen cell co-culture assay. In contrast, the mineral apposition rates were not changed in Col2-Opg transgenic mice. TUNEL staining revealed more apoptotic hypertrophic chondrocytes in the growth plate of Col2-Opg mice. Flow cytometry analysis showed fewer RANK-expressing cells in the marrow of Col2a1-Opg mice, suggesting the role of OPG in blocking the differentiation of early mesenchymal progenitors into RANK-expressing pre-osteoclasts. Our results demonstrated that OPG expression in chondrocyte increases bone mass in the proximal metaphysis of tibiae through negative regulation of osteoclast formation. PMID:26329493

  7. Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture

    PubMed Central

    Kazancioglu, Hakki Oguz; Aksakalli, Sertac; Ezirganli, Seref; Birlik, Muhammet; Esrefoglu, Mukaddes; Acar, Ahmet Hüseyin

    2015-01-01

    Background Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME) has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new applications have been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE) on new bone formation in rat midpalatal suture after RME. Materials and methods Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In the CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess new bone formation. Results New bone formation was significantly greater in the CAPE group than the control group (P<0.05). CAPE enhances new bone formation in midpalatal suture after RME. Conclusion These results show that CAPE may decrease the time needed for retention.

  8. Osteochondrosis Can Lead to Formation of Pseudocysts and True Cysts in the Subchondral Bone of Horses.

    PubMed

    Olstad, K; Østevik, L; Carlson, C S; Ekman, S

    2015-09-01

    Osteochondrosis arises as a result of focal failure of the blood supply to growth cartilage. The current aim was to examine the pathogenesis of pseudocysts and true cysts in subchondral bone following failure of the blood supply to the articular-epiphyseal cartilage complex in horses. Cases were recruited based on identification of lesions (n = 17) that were considered likely to progress to or to represent pseudocysts or true cysts in epiphyseal bone in histological sections and included 10 horses ranging in age from 48 days to 5 years old. Cases comprised 3 warmbloods, 3 Standardbreds, 1 Quarter horse and 1 Arabian with spontaneous lesions and 2 Fjord ponies with experimentally induced lesions. Seven lesions consisted of areas of ischemic chondronecrosis and were compatible with pseudocysts. Two lesions were located at intermediate depth in epiphyseal growth cartilage, 2 lesions were located in the ossification front, 2 lesions were located in epiphyseal bone and 1 lesion was located in the metaphyseal growth plate (physis). Ten lesions contained dilated blood vessels and were compatible with true cysts. In 2 lesions the dilated blood vessels were located within the lumina of failed cartilage canals. In the 8 remaining lesions areas of ischemic chondronecrosis were associated with granulation tissue in the subjacent bone and dilated vessels were located within this granulation tissue. Failure of the blood supply and ischemic chondronecrosis can lead to formation of pseudocysts or dilatation of blood vessels and formation of true cysts in the epiphyseal bone of horses. PMID:25428408

  9. Polypyrrole coating on poly-(lactide/glycolide)-?-tricalcium phosphate screws enhances new bone formation in rabbits.

    PubMed

    Zhao, Ming-Dong; Björninen, Miina; Cao, Lu; Wang, Hui-Ren; Pelto, Jani; Li, Xiang-Qian; Hyttinen, Jari; Jiang, Yun-Qi; Kellomäki, Minna; Miettinen, Susanna; Sándor, George K; Seppänen, Riitta; Haimi, Suvi; Dong, Jian

    2015-01-01

    Polypyrrole (PPy) has gained interest as an implant material due to its multifunctional properties and its high compatibility with several cell and tissue types. For the first time, the biocompatibility and osteointegration of PPy coating, incorporated with chondroitin sulfate (CS), were studied in vivo by implanting PPy-coated bioabsorbable bone fixation composite screws of poly-(lactide/glycolide) copolymer (PLGA) and ?-tricalcium phosphate (TCP) into New Zealand white rabbits. Uncoated bioabsorbable polymer composite screws and commercially available stainless steel cortical screws were used as reference implants. The rabbits were euthanized 12 and 26 weeks after the implantation. The systemic effects were evaluated from food and water consumption, body weight, body temperature, clinical signs, blood samples, internal organ weights, and histological examination. Local effects were studied from bone tissue and surrounding soft tissue histology. New bone formation was evaluated by micro-computed tomography, tetracycline labeling and torsion tests. Torsion tests were performed in order to capture the peak value of the torsion force during the course of the screw's loosening. The coated screws induced significantly more bone formation than the uncoated screws. In addition, none of the implants induced any systemic or local toxicity. The results suggest that PPy is biocompatible with bone tissue and is a potential coating for enhancing osteointegration in orthopedic implants. PMID:26610717

  10. Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation

    PubMed Central

    Yang, Liu; Tsang, Kwok Yeung; Tang, Hoi Ching; Chan, Danny; Cheah, Kathryn S. E.

    2014-01-01

    According to current dogma, chondrocytes and osteoblasts are considered independent lineages derived from a common osteochondroprogenitor. In endochondral bone formation, chondrocytes undergo a series of differentiation steps to form the growth plate, and it generally is accepted that death is the ultimate fate of terminally differentiated hypertrophic chondrocytes (HCs). Osteoblasts, accompanying vascular invasion, lay down endochondral bone to replace cartilage. However, whether an HC can become an osteoblast and contribute to the full osteogenic lineage has been the subject of a century-long debate. Here we use a cell-specific tamoxifen-inducible genetic recombination approach to track the fate of murine HCs and show that they can survive the cartilage-to-bone transition and become osteogenic cells in fetal and postnatal endochondral bones and persist into adulthood. This discovery of a chondrocyte-to-osteoblast lineage continuum revises concepts of the ontogeny of osteoblasts, with implications for the control of bone homeostasis and the interpretation of the underlying pathological bases of bone disorders. PMID:25092332

  11. Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation

    SciTech Connect

    Kimura, Hiroaki; Akiyama, Haruhiko . E-mail: hakiyama@kuhp.kyoto-u.ac.jp; Nakamura, Takashi; Crombrugghe, Benoit de

    2007-05-18

    We identified a cDNA encoding mouse Tenascin-W (TN-W) upregulated by bone morphogenetic protein (Bmp)2 in ATDC5 osteo-chondroprogenitors. In adult mice, TN-W was markedly expressed in bone. In mouse embryos, during endochondral bone formation TN-W was localized in perichondrium/periosteum, but not in trabecular and cortical bones. During bone fracture repair, cells in the newly formed perichondrium/periosteum surrounding the cartilaginous callus expressed TN-W. Furthermore, TN-W was detectable in perichondrium/periosteum of Runx2-null and Osterix-null embryos, indicating that TN-W is expressed in preosteoblasts. In CFU-F and -O cells, TN-W had no effect on initiation of osteogenesis of bone marrow cells, and in MC3T3-E1 osteoblastic cells TN-W inhibited cell proliferation and Col1a1 expression. In addition, TN-W suppressed canonical Wnt signaling which stimulates osteoblastic differentiation. Our results indicate that TN-W is a novel marker of preosteoblasts in early stage of osteogenesis, and that TN-W inhibits cell proliferation and differentiation of preosteoblasts mediated by canonical Wnt signaling.

  12. Assessment of bone formation and bone resorption in osteoporosis: a comparison between tetracycline-based iliac histomorphometry and whole body /sup 85/Sr kinetics

    SciTech Connect

    Reeve, J.; Arlot, M.E.; Chavassieux, P.M.; Edouard, C.; Green, J.R.; Hesp, R.; Tellez, M.; Meunier, P.J.

    1987-12-01

    Bone formation and resorption have been measured in patients with idiopathic osteoporosis by histomorphometry of 7.5-mm trephine biopsies and in the whole body by 85Sr radiotracer methodology and calcium balances. The studies were synchronized and most were preceded by double in vivo tetracycline labeling. Correlations between histological and kinetic bone formation indices were better when better when based on the extent of double tetracycline labels than on measurements of osteoid by visible light microscopy. Correction of the kinetic data for long-term exchange, using 5 months' serial whole body counting of retained 85Sr, improved the fit of the kinetic to the histological data. A statistical analysis of the measurement uncertainties showed that the residual scatter in the best correlations (between exchange-corrected bone formation rates and double-labeled osteoid surface indices) could be attributed to measurement imprecision alone. The exchange-corrected resorption rate correlated fairly well with iliac trabecular resorption surfaces, and using a volume referent rather than a surface referent for the histological index improved the statistical fit when patients with therapeutically accelerated bone turnover were included. A much better correlation was obtained by including osteoid volume acting as an independent predictor of bone resorption in a bivariate regression with a resorption surface index. The residual errors could then be accounted for by known measurement uncertainties. Whereas osteoid taking a double label closely predicted the kinetic rate of bone formation, further analysis suggested that osteoid that took no label or a single label was more closely related to bone resorption, presumably as a secondary result of the coupling of bone formation to bone resorption.

  13. Fabrication and Characterization of Biomimetic Collagen-Apatite Scaffolds with Tunable Structures for Bone Tissue Engineering

    PubMed Central

    Xia, Zengmin; Yu, Xiaohua; Jiang, Xi; Brody, Harold D; Rowe, David W; Wei, Mei

    2013-01-01

    The objective of the current study is to prepare a biomimetic collagen-apatite (Col-Ap) scaffold for improved bone repair and regeneration. A novel bottom-up approach has been developed, which combines a biomimetic self-assembly method with a controllable freeze casting technology. In this study, the mineralized collagen fibers were generated using a simple one-step co-precipitation method which involved collagen self-assembly and in situ apatite precipitation in a collagen-containing modified simulated body fluid (m-SBF). The precipitates were subjected to controllable freeze casting, forming scaffolds with either an isotropic equiaxed structure or a unidirectional lamellar structure. These scaffolds were comprised of collagen fibers and poorly crystalline bone-like carbonated apatite nanoparticles. The mineral content in the scaffold could be tailored in a range 0–54 wt% by simply adjusting the collagen content in the m-SBF. Further, the mechanisms of the formation of both the equiaxed and the lamellar scaffolds were investigated, and freezing regimes for equiaxed and lamellar solidification were established. Finally, bone forming capability of such prepared scaffolds was evaluated in vivo in a mouse calvarial defect model. It was confirmed that the scaffolds well support new bone formation. PMID:23567944

  14. Development of silk-based scaffolds for tissue engineering of bone from human adipose derived stem cells

    PubMed Central

    Correia, Cristina; Bhumiratana, Sarindr; Yan, Le-Ping; Oliveira, Ana L.; Gimble, Jeffrey M.; Rockwood, Danielle; Kaplan, David L.; Sousa, Rui A.; Reis, Rui L.; Vunjak-Novakovic, Gordana

    2012-01-01

    Silk fibroin is a potent alternative to other biodegradable biopolymers for bone tissue engineering (TE), because of its tunable architecture and mechanical properties, and demonstrated ability to support bone formation, in vitro and in vivo. In this study, we investigated a range of silk scaffolds for bone TE using human adipose-derived stem cells (hASC), an attractive cell source for engineering autologous bone grafts. Our goal was to understand the effects of scaffold architecture and biomechanics and use this information to optimize silk scaffolds for bone TE applications. Silk scaffolds were fabricated using different solvents (aqueous vs. hexafluoro-2-propanol - HFIP), pore sizes (250–500?m vs. 500–1000?m) and structures (lamellar vs. spherical pores). Four types of silk scaffolds combining the properties of interest were systematically compared with respect to bone tissue outcomes with decellularized trabecular bone (DCB) included as a “gold standard”. The scaffolds were seeded with hASC and cultured for 7 weeks in osteogenic media. Bone formation was evaluated by cell proliferation and differentiation, matrix production, calcification and mechanical properties. We observed that 400–600?m porous HFIP-derived silk fibroin scaffold demonstrated the best bone tissue formation outcomes as evidenced by increased bone protein production (osteopontin, collagen type I, bone sialoprotein), enhanced calcium deposition and total bone volume. On a direct comparison basis, alkaline phosphatase activity (AP) at week 2, and new calcium deposition at week 7 were comparable to the cells cultured in DCB. Yet, among the aqueous-based structures, the lamellar architecture induced increased AP activity and demonstrated higher equilibrium modulus than the spherical-pore scaffolds. Based on the collected data, we propose a conceptual model describing the effects of silk scaffold design on bone tissue formation. PMID:22421311

  15. Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

    PubMed

    Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

    2016-01-01

    Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-?1 and TGF-? receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. PMID:25899717

  16. Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts

    PubMed Central

    Keller, Johannes; Catala-Lehnen, Philip; Huebner, Antje K.; Jeschke, Anke; Heckt, Timo; Lueth, Anja; Krause, Matthias; Koehne, Till; Albers, Joachim; Schulze, Jochen; Schilling, Sarah; Haberland, Michael; Denninger, Hannah; Neven, Mona; Hermans-Borgmeyer, Irm; Streichert, Thomas; Breer, Stefan; Barvencik, Florian; Levkau, Bodo; Rathkolb, Birgit; Wolf, Eckhard; Calzada-Wack, Julia; Neff, Frauke; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrab?; Klutmann, Susanne; Tsourdi, Elena; Hofbauer, Lorenz C.; Kleuser, Burkhard; Chun, Jerold; Schinke, Thorsten; Amling, Michael

    2014-01-01

    The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signaling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P3. Finally, pharmacologic treatment with the non-selective S1P receptor agonist FTY720 causes increased bone formation in wildtype, but not in S1P3-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo, and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts. PMID:25333900

  17. Effects of epidermal growth factor on bone formation and resorption in vivo

    SciTech Connect

    Marie, P.J.; Hott, M.; Perheentupa, J. )

    1990-02-01

    The effects of mouse epidermal growth factor (EGF) on bone formation and resorption were examined in male mice. EGF administration (2-200 ng.g-1.day-1 ip for 7 days) induced a dose-dependent rise in plasma EGF levels that remained within physiological range. Histomorphometric analysis of caudal vertebrae showed that EGF (20 and 200 ng.g-1.day-1) reduced the endosteal matrix and mineral appositional rates after 5 days of treatment as measured by double (3H)proline labeling and double tetracycline labeling, respectively. This effect was transitory and was not observed after 7 days of EGF administration. EGF administered for 7 days induced a dose-dependent increase in the periosteal osteoblastic and tetracycline double-labeled surfaces. At high dosage (200 ng.g-1.day-1) EGF administration increased the osteoclastic surface and the number of acid phosphatase-stained osteoclasts, although plasma calcium remained normal. The results show that EGF administration at physiological doses induces distinct effects on endosteal and periosteal bone formation and that the effects are dependent on EGF dosage and duration of treatment. This study indicates that EGF at physiological dosage stimulates periosteal bone formation and increases endosteal bone resorption in the growing mouse.

  18. Insulin-like growth factor-1 receptor in mature osteoblasts is required for periosteal bone formation induced by reloading

    NASA Astrophysics Data System (ADS)

    Kubota, Takuo; Elalieh, Hashem Z.; Saless, Neema; Fong, Chak; Wang, Yongmei; Babey, Muriel; Cheng, Zhiqiang; Bikle, Daniel D.

    2013-11-01

    Skeletal loading and unloading has a pronounced impact on bone remodeling, a process also regulated by insulin-like growth factor-1 (IGF-1) signaling. Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while reloading after unloading restores responsiveness to IGF-1. However, a direct study of the importance of IGF-1 signaling in the skeletal response to mechanical loading remains to be tested. In this study, we assessed the skeletal response of osteoblast-specific Igf-1 receptor deficient (Igf-1r-/-) mice to unloading and reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16 days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal and endosteal bone formation at baseline. Periosteal and endosteal bone formation decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal bone formation with reloading was completely inhibited in Igf-1r-/- mice, although reloading-induced endosteal bone formation was not hampered. These changes in bone formation resulted in the abolishment of the expected increase in total cross-sectional area with reloading in Igf-1r-/- mice compared to the control mice. These results suggest that the Igf-1r in mature osteoblasts has a critical role in periosteal bone formation in the skeletal response to mechanical loading.

  19. Oxidized lipid depresses canine growth, immune function, and bone formation.

    PubMed

    Turek, John J; Watkins, Bruce A; Schoenlein, Ingrid A; Allen, Kenneth G D; Hayek, Michael G; Aldrich, C Gregory

    2003-01-01

    Dietary oxidized lipids can increase oxidative stress and potentially contribute to a variety of disease syndromes. This research describes the first use of a canine model to assess the effects of dietary oxidized lipids on growth, antioxidant status, and some immune functions. Three groups of eight, two-month old coon-hound puppies were pair fed diets for 16 weeks. The control diet contained <50 ppm aldehydes, and two additional diets contained thermally oxidized lipids targeted to contain 100 ppm aldehydes (medium-oxidation) and 500 ppm aldehydes (high-oxidation). Dogs fed the high-oxidation diet weighed less than those from the medium-oxidation (P < 0.05) and control groups (P < 0.001) at the end of the study. Oxidized lipids reduced serum vitamin E levels, total body fat content, and bone appositional rate. At different time points of the study, peripheral blood neutrophils and monocytes from dogs fed the HO diet had reduced oxidative burst capacity and produced less superoxide and hydrogen peroxide when stimulated with phorbol esters compared to the control group. Lymphocyte blastogenesis in response to concanavalin A was suppressed by dietary oxidized lipid. This study indicates that dietary oxidized lipids negatively affect the growth, antioxidant status, and some immune functions of dogs. Importantly, some effects are evident at 100 ppm aldehydes in the diet, which is a moderate level of oxidation. The rapid growth and weight gain of the dog during the first 6 months of life may also provide a better model for assessing the risks of dietary oxidized lipid in children and adolescents than previously used rodent models. PMID:12559474

  20. Inkjet-Based Biopatterning of Bone Morphogenetic Protein-2 to Spatially Control Calvarial Bone Formation

    E-print Network

    Weiss, Lee E.

    of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns. Introduction Spatial patterning of cell of persistent patterns of a broad array of growth factors and their modifying molecules, leading to functional

  1. Biomodification of PCL Scaffolds with Matrigel, HA, and SR1 Enhances De Novo Ectopic Bone Marrow Formation Induced by rhBMP-2.

    PubMed

    Bao, Wenjing; Gao, Mei; Cheng, Yanyan; Lee, Hyun Jae; Zhang, Qinghao; Hemingway, Susan; Luo, Zhibo; Krol, Andrzej; Yang, Guanlin; An, Jing

    2015-01-01

    The de novo formation of ectopic bone marrow was induced using 1.2-mm-thin polycaprolactone (PCL) scaffolds biomodified with several different biomaterials. In vivo investigations of de novo bone and bone marrow formation indicated that subcutaneous implantation of PCL scaffolds coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) plus Matrigel, hydroxyapatite (HA), or StemRegenin 1 (SR1) improved formation of bone and hematopoietic bone marrow as determined by microcomputed tomography, and histological and hematopoietic characterizations. Our study provides evidence that thin PCL scaffolds biomodified with Matrigel, HA, and SR1 mimic the environments of real bone and bone marrow, thereby enhancing the de novo ectopic bone marrow formation induced by rhBMP-2. This ectopic bone marrow model will serve as a unique and essential tool for basic research and for clinical applications of postnatal tissue engineering and organ regeneration. PMID:26309805

  2. Biomodification of PCL Scaffolds with Matrigel, HA, and SR1 Enhances De Novo Ectopic Bone Marrow Formation Induced by rhBMP-2

    PubMed Central

    Bao, Wenjing; Gao, Mei; Cheng, Yanyan; Lee, Hyun Jae; Zhang, Qinghao; Hemingway, Susan; Luo, Zhibo; Krol, Andrzej; Yang, Guanlin; An, Jing

    2015-01-01

    Abstract The de novo formation of ectopic bone marrow was induced using 1.2-mm-thin polycaprolactone (PCL) scaffolds biomodified with several different biomaterials. In vivo investigations of de novo bone and bone marrow formation indicated that subcutaneous implantation of PCL scaffolds coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) plus Matrigel, hydroxyapatite (HA), or StemRegenin 1 (SR1) improved formation of bone and hematopoietic bone marrow as determined by microcomputed tomography, and histological and hematopoietic characterizations. Our study provides evidence that thin PCL scaffolds biomodified with Matrigel, HA, and SR1 mimic the environments of real bone and bone marrow, thereby enhancing the de novo ectopic bone marrow formation induced by rhBMP-2. This ectopic bone marrow model will serve as a unique and essential tool for basic research and for clinical applications of postnatal tissue engineering and organ regeneration. PMID:26309805

  3. Malignant fibrous histiocytoma of soft tissue with metaplastic bone and cartilage formation

    SciTech Connect

    Dorfman, H.D.; Bhagavan, B.S.

    1982-05-01

    The presence of bone and cartilage in some cases of malignant fibrous histiocytoma of the soft tissue as a microscopic finding has been reported previously but little note has been taken of the radiologic manifestations of these tumor elements. A series of five such cases with sufficient metaplastic osseous and cartilaginous elements to produce roentgenographic evidence of their presence is reported here. An additional two cases showed only histologic evidence of bone or cartilage formation. The reactive ossification tends to be peripheral in location, involving the pseudocapsule of the sarcoma or its fibrous septa. In three there was a zoning pattern with peripheral or polar orientation, strongly suggesting the diagnosis of myositis ossificans. The latter was the diagnosis considered radiologically in four of the five cases. Malignant fibrous histiocytoma with reactive bone and cartilage must be considered in the differential diagnosis of soft tissue masses with calcific densities, particularly when these occur in tumors of the extremities.

  4. In Vivo Ectopic Bone Formation by Devitalized Mineralized Stem Cell Carriers Produced Under Mineralizing Culture Condition

    PubMed Central

    Chai, Yoke Chin; Geris, Liesbet; Bolander, Johanna; Pyka, Grzegorz; Van Bael, Simon; Luyten, Frank P.

    2014-01-01

    Abstract Functionalization of tissue engineering scaffolds with in vitro–generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem cells in vitro. However, the bone-forming capacity of these constructs (seeded with or without cells) is so far not apparent. In this study, we aimed at developing a mineralizing culture condition to biofunctionalize three-dimensional (3D) porous scaffolds with highly mineralized ECM in order to produce devitalized, osteoinductive mineralized carriers for human periosteal-derived progenitors (hPDCs). For this, three medium formulations [i.e., growth medium only (BM1), with ascorbic acid (BM2), and with ascorbic acid and dexamethasone (BM3)] supplemented with calcium (Ca2+) and phosphate (PO43?) ions simultaneously as mineralizing source were investigated. The results showed that, besides the significant impacts on enhancing cell proliferation (the highest in BM3 condition), the formulated mineralizing media differentially regulated the osteochondro-related gene markers in a medium-dependent manner (e.g., significant upregulation of BMP2, bone sialoprotein, osteocalcin, and Wnt5a in BM2 condition). This has resulted in distinguished cell populations that were identifiable by specific gene signatures as demonstrated by the principle component analysis. Through devitalization, mineralized carriers with apatite crystal structures unique to each medium condition (by X-ray diffraction and SEM analysis) were obtained. Quantitatively, BM3 condition produced carriers with the highest mineral and collagen contents as well as human-specific VEGF proteins, followed by BM2 and BM1 conditions. Encouragingly, all mineralized carriers (after reseeded with hPDCs) induced bone formation after 8 weeks of subcutaneous implantation in nude mice models, with BM2-carriers inducing the highest bone volume, and the lowest in the BM3 condition (as quantitated by nano-computed tomography [nano-CT]). Histological analysis revealed different bone formation patterns, either bone ossicles containing bone marrow surrounding the scaffold struts (in BM2) or bone apposition directly on the struts' surface (in BM1 and BM3). In conclusion, we have presented experimental data on the feasibility to produce devitalized osteoinductive mineralized carriers by functionalizing 3D porous scaffolds with an in vitro cell-made mineralized matrix under the mineralizing culture conditions. PMID:25469312

  5. In vivo ectopic bone formation by devitalized mineralized stem cell carriers produced under mineralizing culture condition.

    PubMed

    Chai, Yoke Chin; Geris, Liesbet; Bolander, Johanna; Pyka, Grzegorz; Van Bael, Simon; Luyten, Frank P; Schrooten, Jan

    2014-12-01

    Functionalization of tissue engineering scaffolds with in vitro-generated bone-like extracellular matrix (ECM) represents an effective biomimetic approach to promote osteogenic differentiation of stem cells in vitro. However, the bone-forming capacity of these constructs (seeded with or without cells) is so far not apparent. In this study, we aimed at developing a mineralizing culture condition to biofunctionalize three-dimensional (3D) porous scaffolds with highly mineralized ECM in order to produce devitalized, osteoinductive mineralized carriers for human periosteal-derived progenitors (hPDCs). For this, three medium formulations [i.e., growth medium only (BM1), with ascorbic acid (BM2), and with ascorbic acid and dexamethasone (BM3)] supplemented with calcium (Ca(2+)) and phosphate (PO4 (3-)) ions simultaneously as mineralizing source were investigated. The results showed that, besides the significant impacts on enhancing cell proliferation (the highest in BM3 condition), the formulated mineralizing media differentially regulated the osteochondro-related gene markers in a medium-dependent manner (e.g., significant upregulation of BMP2, bone sialoprotein, osteocalcin, and Wnt5a in BM2 condition). This has resulted in distinguished cell populations that were identifiable by specific gene signatures as demonstrated by the principle component analysis. Through devitalization, mineralized carriers with apatite crystal structures unique to each medium condition (by X-ray diffraction and SEM analysis) were obtained. Quantitatively, BM3 condition produced carriers with the highest mineral and collagen contents as well as human-specific VEGF proteins, followed by BM2 and BM1 conditions. Encouragingly, all mineralized carriers (after reseeded with hPDCs) induced bone formation after 8 weeks of subcutaneous implantation in nude mice models, with BM2-carriers inducing the highest bone volume, and the lowest in the BM3 condition (as quantitated by nano-computed tomography [nano-CT]). Histological analysis revealed different bone formation patterns, either bone ossicles containing bone marrow surrounding the scaffold struts (in BM2) or bone apposition directly on the struts' surface (in BM1 and BM3). In conclusion, we have presented experimental data on the feasibility to produce devitalized osteoinductive mineralized carriers by functionalizing 3D porous scaffolds with an in vitro cell-made mineralized matrix under the mineralizing culture conditions. PMID:25469312

  6. Follistatin-like 3 is a mediator of exercise-driven bone formation and strengthening.

    PubMed

    Nam, J; Perera, P; Gordon, R; Jeong, Y H; Blazek, A D; Kim, D G; Tee, B C; Sun, Z; Eubank, T D; Zhao, Y; Lablebecioglu, B; Liu, S; Litsky, A; Weisleder, N L; Lee, B S; Butterfield, T; Schneyer, A L; Agarwal, S

    2015-09-01

    Exercise is vital for maintaining bone strength and architecture. Follistatin-like 3 (FSTL3), a member of follistatin family, is a mechanosensitive protein upregulated in response to exercise and is involved in regulating musculoskeletal health. Here, we investigated the potential role of FSTL3 in exercise-driven bone remodeling. Exercise-dependent regulation of bone structure and functions was compared in mice with global Fstl3 gene deletion (Fstl3-/-) and their age-matched Fstl3+/+ littermates. Mice were exercised by low-intensity treadmill walking. The mechanical properties and mineralization were determined by ?CT, three-point bending test and sequential incorporation of calcein and alizarin complexone. ELISA, Western-blot analysis and qRT-PCR were used to analyze the regulation of FSTL3 and associated molecules in the serum specimens and tissues. Daily exercise significantly increased circulating FSTL3 levels in mice, rats and humans. Compared to age-matched littermates, Fstl3-/- mice exhibited significantly lower fracture tolerance, having greater stiffness, but lower strain at fracture and yield energy. Furthermore, increased levels of circulating FSTL3 in young mice paralleled greater strain at fracture compared to the lower levels of FSTL3 in older mice. More significantly, Fstl3-/- mice exhibited loss of mechanosensitivity and irresponsiveness to exercise-dependent bone formation as compared to their Fstl3+/+ littermates. In addition, FSTL3 gene deletion resulted in loss of exercise-dependent sclerostin regulation in osteocytes and osteoblasts, as compared to Fstl3+/+ osteocytes and osteoblasts, in vivo and in vitro. The data identify FSTL3 as a critical mediator of exercise-dependent bone formation and strengthening and point to its potential role in bone health and in musculoskeletal diseases. PMID:25937185

  7. Cherubism Gene Sh3bp2 is Important for Optimal Bone Formation, Osteoblast Differentiation and Function

    PubMed Central

    Mukherjee, Padma M.; Wang, Chiachien J.; Chen, I-Ping; Jafarov, Toghrul; Olsen, Bjorn R.; Ueki, Yasuyoshi; Reichenberger, Ernst J.

    2012-01-01

    Introduction Cherubism is a human genetic disorder that causes bilateral symmetrical enlargement of the maxilla and mandible in children. It is caused by mutations in SH3BP2. The exact pathogenesis of the disorder is an area of active research. Sh3bp2 knock-in mice were developed by introducing a Pro416Arg mutation (Pro418Arg in humans) in the mouse genome. The osteoclast phenotype of this mouse model was recently described. Methods We examined the bone phenotype of the cherubism mouse model, the role of Sh3bp2 during bone formation, osteoblast differentiation and osteoblast function. Results We observed delays in early postnatal development of homozygous Sh3bp2KI/KI mice. Sh3bp2KI/KI mice exhibit increased growth plate thickness and significantly decreased trabecular bone thickness and reduced bone mineral density. Histomorphometric and ?-CT analyses reveal bone loss in cranial and appendicular skeleton. Sh3bp2KI/KI mice also exhibit a significant decrease in osteoid formation that indicates a defect in osteoblast function. Calvarial osteoblast cell cultures exhibit a decrease in alkaline phosphatase expression and mineralization suggesting reduced differentiation potential. Gene expression of osteoblast differentiation markers like collagen type-I, alkaline phosphatase and osteocalcin are decreased in osteoblast cultures from Sh3bp2KI/KI mice. Conclusions These data suggest that Sh3bp2 function regulates bone homeostasis not only through osteoclast-specific effects but also through effects on osteoblast differentiation and function. PMID:20691350

  8. Effect of paleosol formation on rare earth element signatures in fossil bone

    NASA Astrophysics Data System (ADS)

    Metzger, Christine A.; Terry, Dennis O., Jr.; Grandstaff, David E.

    2004-06-01

    The rare earth element (REE) content of fossil bones was analyzed and compared with the degree of ancient pedogenic development and depositional environments from several locations in the Orellan Scenic Member of the Oligocene Brule Formation in Badlands National Park, South Dakota. Paleosols ranged from weakly developed Entisols to more strongly developed Inceptisols, all typical of fluvial environments and possible paleocatena variation. Paleosols were alkaline and well drained. Sediments with sparse soil features from an oxbow lake system suggest that conditions were too waterlogged and sedimentation rates too rapid for significant pedogenesis. The variance of REE signatures in fossil bones from the paleosol sites was significantly greater than that of fossils from minimally altered sediments of the former oxbow lake. Positive Ce anomalies were associated with low U concentrations and indicate paleoredox conditions. Greater degrees of pedogenesis, regardless of the horizon in which the bone was found, systematically correlated with increased heavy REE enrichment in fossil bones. The fossil-bone REE signatures from the different paleosols and depositional environments were significantly different and distinguishable.

  9. TGF-?/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation

    PubMed Central

    Rahman, Md Shaifur; Akhtar, Naznin; Jamil, Hossen Mohammad; Banik, Rajat Suvra; Asaduzzaman, Sikder M

    2015-01-01

    Transforming growth factor-beta (TGF-?)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-?/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-? (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-?/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-?/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and ?-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-?/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics. PMID:26273537

  10. Zfp521 antagonizes Runx2, delays osteoblast differentiation in vitro, and promotes bone formation in vivo.

    PubMed

    Wu, Meilin; Hesse, Eric; Morvan, Frederic; Zhang, Jian-Ping; Correa, Diego; Rowe, Glenn C; Kiviranta, Riku; Neff, Lynn; Philbrick, William M; Horne, William C; Baron, Roland

    2009-04-01

    Zfp521, a 30 C2H2 Kruppel-like zinc finger protein, is expressed at high levels at the periphery of early mesenchymal condensations prefiguring skeletal elements and in all developing bones in the perichondrium and periosteum, in osteoblast precursors and osteocytes, and in chondroblast precursors and growth plate prehypertrophic chondrocytes. Zfp521 expression in cultured mesenchymal cells is decreased by BMP-2 and increased by PTHrP, which promote and antagonize osteoblast differentiation, respectively. In vitro, Zfp521 overexpression reduces the expression of several downstream osteoblast marker genes and antagonizes osteoblast differentiation. Zfp521 binds Runx2 and represses its transcriptional activity, and Runx2 dose-dependently rescues Zfp521's inhibition of osteoblast differentiation. In contrast, osteocalcin promoter-targeted overexpression of Zfp521 in osteoblasts in vivo results in increased bone formation and bone mass. We propose that Zfp521 regulates the rate of osteoblast differentiation and bone formation during development and in the mature skeleton, in part by antagonizing Runx2. PMID:19095088

  11. Effects of Low-Intensity Pulsed Ultrasound on New Trabecular Bone during Bone–Tendon Junction Healing in a Rabbit Model: A Synchrotron Radiation Micro-CT Study

    PubMed Central

    Lu, Hongbin; Zheng, Cheng; Wang, Zhanwen; Chen, Can; Chen, Huabin; Hu, Jianzhong

    2015-01-01

    This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone–tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone–tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone–tendon junction injury model at the patella–patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week) and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point). The patella–patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone–tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promot bone formation and remodeling of new trabecular bone during the bone–tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate the microarchitecture of new bone in bone–tendon junction. PMID:25874957

  12. Removing the bone brake.

    PubMed

    Schett, Georg; Bozec, Aline

    2014-09-01

    Osteoporosis results from an imbalance between bone resorption and bone formation. While bone resorption inhibitors are widely used to treat osteoporosis, stimulating bone formation is more challenging. Recently, McClung et al. (2014) found that neutralization of sclerostin, a potent inhibitor of bone formation, effectively increased bone mass in postmenopausal women. PMID:25185946

  13. Changes in markers of bone formation and resorption in a bed rest model of weightlessness

    NASA Technical Reports Server (NTRS)

    Lueken, S. A.; Arnaud, S. B.; Taylor, A. K.; Baylink, D. J.

    1993-01-01

    To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

  14. Increased Resistance during Jump Exercise Does Not Enhance Cortical Bone Formation

    PubMed Central

    Boudreaux, Ramon D.; Swift, Joshua M.; Gasier, Heath G.; Wiggs, Michael P.; Hogan, Harry A.; Fluckey, James D.; Bloomfield, Susan A.

    2014-01-01

    PURPOSE This study sought to elucidate the effects of a low- and high-load jump resistance exercise (RE) training protocol on cortical bone of the tibia and femur mid-diaphyses. METHODS Sprague-Dawley rats (male, 6-mos-old) were randomly assigned to high-load RE (HRE; n = 16), low-load RE (LRE; n = 15) or cage control (CC; n = 11) groups. Animals in the HRE and LRE groups performed 15 sessions of jump RE for 5 weeks. Load in the HRE group was progressively increased from 80g added to a weighted vest (50 repetitions) to 410g (16 repetitions). The LRE rats completed the same protocol as the HRE group (same number of repetitions) with only a 30g vest applied. RESULTS Low- and high-load jump RE resulted in 6–11% higher cortical bone mineral content (BMC) and cortical bone area compared to controls as determined by in vivo pQCT measurements. In the femur, however, only LRE demonstrated improvements in cortical volumetric bone mineral density (vBMD; +11%) and cross-sectional moment of inertia (CSMI; +20%) versus CC group. Three-point bending to failure revealed a marked increase in tibial max force (25–29%), stiffness (19–22%), and energy to max force (35–55%), and a reduction in elastic modulus (?11–14%) in both LRE and HRE compared to controls. Dynamic histomorphometry assessed at the tibia mid-diaphysis determined that both LRE and HRE resulted in 20–30% higher periosteal mineralizing surface versus CC group. Mineral apposition rate (MAR) and bone formation rate (BFR) were significantly greater in LRE animals (27%, 39%) than in the HRE group. CONCLUSION These data demonstrate that jump training with minimal loading is equally, and sometimes more, effective at augmenting cortical bone integrity compared to overload training in skeletally mature rats. PMID:24743108

  15. Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium

    PubMed Central

    Rakian, Audrey; Yang, Wu-Chen; Gluhak-Heinrich, Jelica; Cui, Yong; Harris, Marie A; Villarreal, Demitri; Feng, Jerry Q; MacDougall, Mary; Harris, Stephen E

    2013-01-01

    Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey's fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp7+ (Osterix+) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and ?-SMA+ cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOSp7-Cre-EGFP. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOSp7-Cre-EGFP. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation. PMID:23807640

  16. Spinal entheseal new bone formation: the early changes of spinal diffuse idiopathic skeletal hyperostosis.

    PubMed

    Fornasier, V L; Littlejohn, G; Urowitz, M B; Keystone, E C; Smythe, H A

    1983-12-01

    Diffuse idiopathic skeletal hyperostosis is characterized by new bone growth at the point of insertion of ligaments and tendons to bone. We examined retrospectively the anatomical morphologic changes discernible at the insertion of spinal longitudinal ligamentous fibrous tissue to vertebral bodies. The earliest evidence of bone formation was in the "waist" of the vertebral body away from the intervertebral disc area. New bone arose along the insertion of the fibrous tissue to the anterior cortical surface of the vertebral body and progressed along the fibres at an angle to the cortical surface distinct from it until the advanced stages. With disc degeneration the 2 processes were distinct and separate. Degenerative disc disease occurred at the margin of the endplate of the vertebral body with associated changes in the disc itself. Entheseal ossification occurred remote from the margin of the intervertebral disc and remained distinct from the subjacent vertebral body as it followed the ligamentous tissue; fusion with the cortical surface of the subjacent vertebral body was only seen in the most advanced cases of disseminated idiopathic systemic hyperostosis. PMID:6420561

  17. Radiation-blocking shields to localize periarticular radiation precisely for prevention of heterotopic bone formation around uncemented total hip arthroplasties

    SciTech Connect

    Jasty, M.; Schutzer, S.; Tepper, J.; Willett, C.; Stracher, M.A.; Harris, W.H. )

    1990-08-01

    Sixteen patients (18 hips) were treated with localized radiation therapy limited to periarticular regions surrounding the femoral neck by shielding the prosthesis and the adjacent regions to prevent heterotopic bone formation around the uncemented prosthesis. All hips received 1500 rads. Eight of these hips were irradiated after excising severe heterotopic bone, five because they developed extensive heterotopic ossification in the opposite hip, and five others because they were considered to be at high risk for developing heterotopic ossification. Only two of the 18 hips developed a small amount of heterotopic bone after localized periarticular radiation. All wounds healed primarily. No progressive radiolucencies developed at the bone-prosthesis interface. There was only one trochanteric nonunion of six trochanteric osteotomies. Localized periarticular radiation therapy with precision shielding of the prosthetic components and adjacent skeletal structures is an effective means to prevent heterotopic bone formation around cementless total hip arthroplasties. It also has the advantage of not adversely affecting the healing of the trochanteric osteotomy.

  18. Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women

    SciTech Connect

    Thomsen, K.; Riis, B.; Christiansen, C.

    1986-12-01

    The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of /sup 99m/technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss.

  19. Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.

    PubMed

    Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

    2014-10-01

    Eldecalcitol (ELD), a 2?-hydroxypropyloxy derivative of 1?,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05?g/kg) or ALF (0.2 or 0.4?g/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05?g/kg group were comparable to those of the ALF 0.2?g/kg group. ELD 0.05?g/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (p<0.001) and the ALF 0.2?g/kg group (p<0.05) evaluated by 3-point bending test. The cortical area of the mid-femur in the ELD 0.05?g/kg group but not the ALF 0.2?g/kg group was significantly higher than those of the vehicle control group (p<0.001). Bone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05?g/kg) was greater than that by ALF (0.2?g/kg). In contrast, in the femoral periosteal surface, ELD 0.05?g/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (p<0.05, p<0.01, respectively), whereas ALF 0.2?g/kg did not alter these parameters. These results indicate that ELD improved the biomechanical properties of femoral cortical bone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. PMID:24189542

  20. Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo

    PubMed Central

    Sutha, Ken; Schwartz, Zvi; Wang, Yun; Hyzy, Sharon; Boyan, Barbara D.; McDevitt, Todd C.

    2015-01-01

    The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material (EBM) was compared to DBM in a standard in vivo ectopic osteoinduction assay in nude mice. EBM derived from EBs differentiated for 10 days with osteogenic media (+?-glycerophosphate) exhibited similar osteoinductivity to active DBM (osteoinduction score?=?2.50?±?0.27 vs. 2.75?±?0.16) based on histological scoring, and exceeded inactive DBM (1.13?±?0.13, p?formation of new bone, ossicles, and marrow spaces, similar to active DBM. The potent osteoinductivity of EBM demonstrates that morphogenic factors expressed by ESCs undergoing osteogenic differentiation yield a novel devitalized material capable of stimulating de novo bone formation in vivo. PMID:25961152

  1. Kartogenin induces cartilage-like tissue formation in tendon–bone junction

    PubMed Central

    Zhang, Jianying; Wang, James H-C

    2014-01-01

    Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

  2. Mesenchymal Stem Cells Systemically Injected into Femoral Marrow of Dogs Home to Mandibular Defects to Enhance New Bone Formation

    PubMed Central

    Liu, Xian; Liao, Xuejuan; Luo, En; Chen, Wenchuan; Xu, Hockin H.K.

    2014-01-01

    Musculoskeletal diseases cost the U.S. $849 billion annually. To date, there has been no proof that remote long bone mesenchymal stem cells (BMSC) can home to craniofacial defects for bone regeneration. There has been no report that systemic BMSC injection can increase new bone formation in large animals. The objectives of this study were to use a sex-mismatched canine model for systemic BMSC injection and homing to mandibular defects and to investigate appendicular BMSC migration to craniofacial defects to increase new bone formation. Male beagle dog BMSC were injected into the femoral marrow cavity of female dogs upon which mandibular defects were created. The dogs were sacrificed at 6 weeks. Cells with Y chromosome markers were detected in defects of female dogs with systemic male BMSC injection, indicating the homing of the transplanted BMSC from femoral marrow to the mandibular defect. New bone formation in dogs with systemic BMSC injection was 20–40% higher than control without BMSC injection (p<0.05). Mineralized new bone percentage was increased by 20–40% due to systemic BMSC injection (p<0.05). In conclusion, this study proved that (1) allogeneic BMSC injected into long bone marrow are capable of homing to both appendicular and craniofacial bone in large animals and (2) systemically injected BMSC can significantly increase new bone formation in dog's mandibular defects. These results may help advance the understanding of stem cell homing and present a therapy to enhance bone repair, which may have a wide applicability to the regenerative medicine field. PMID:24125551

  3. A novel therapeutic approach with Caviunin-based isoflavonoid that en routes bone marrow cells to bone formation via BMP2/Wnt-?-catenin signaling

    PubMed Central

    Kushwaha, P; Khedgikar, V; Gautam, J; Dixit, P; Chillara, R; Verma, A; Thakur, R; Mishra, D P; Singh, D; Maurya, R; Chattopadhyay, N; Mishra, P R; Trivedi, R

    2014-01-01

    Recently, we reported that extract of Dalbergia sissoo made from leaves and pods have antiresorptive and bone-forming effects. The positive skeletal effect attributed because of active molecules present in the extract of Dalbergia sissoo. Caviunin 7-O-[?-D-apiofuranosyl-(1-6)-?-D-glucopyranoside] (CAFG), a novel isoflavonoid show higher percentage present in the extract. Here, we show the osteogenic potential of CAFG as an alternative for anabolic therapy for the treatment of osteoporosis by stimulating bone morphogenetic protein 2 (BMP2) and Wnt/?-catenin mechanism. CAFG supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur and decreased bone turnover markers better than genistein. Oral administration of CAFG to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased the expression of osteogenic genes in femur and show new bone formation without uterine hyperplasia. CAFG increased mRNA expression of osteoprotegerin in bone and inhibited osteoclast activation by inhibiting the expression of skeletal osteoclastogenic genes. CAFG is also an effective accelerant for chondrogenesis and has stimulatory effect on the repair of cortical bone after drill-hole injury at the tissue, cell and gene level in mouse femur. At cellular levels, CAFG stimulated osteoblast proliferation, survival and differentiation. Signal transduction inhibitors in osteoblast demonstrated involvement of p-38 mitogen-activated protein kinase pathway stimulated by BMP2 to initiate Wnt/?-catenin signaling to reduce phosphorylation of GSK3-? and subsequent nuclear accumulation of ?-catenin. Osteogenic effects were abrogated by Dkk1, Wnt-receptor blocker and FH535, inhibitor of TCF-complex by reduction in ?-catenin levels. CAFG modulated MSC responsiveness to BMP2, which promoted osteoblast differentiation via Wnt/?-catenin mechanism. CAFG at 1?mg/kg/day dose in ovariectomy mice (human dose ?0.081?mg/kg) led to enhanced bone formation, reduced bone resorption and bone turnover better than well-known phytoestrogen genistein. Owing to CAFG's inherent properties for bone, it could be positioned as a potential drug, food supplement, for postmenopausal osteoporosis and fracture repair. PMID:25232676

  4. An Unusual Traumatic Lamellar Laceration of Cornea

    PubMed Central

    Karkhanis, Amar; Shitole, Satish C

    2015-01-01

    Lamellar laceration of the cornea may occur following ocular trauma. The management of lamellar laceration will depend on whether the lacerated corneal flaps are displaced or undisplaced. We hereby report an unusual case of large traumatic lamellar corneal laceration in right eye in a 14-year-old girl presenting with diminution of vision. Slit lamp biomicroscopic examination showed partial thickness corneal flap of 11.5mm X 7mm from 11o’clock to 6 o’clock position with 3 mm superonasal displacement associated with stromal folds and shifting of inferior limbus and conjunctiva. Surgery was the appropriate option which included visualization of inferior limbus by incising conjunctiva, repositioning of displaced corneal flap and securing it with sutures. Immediate examination and proper surgical management of lamellar corneal injuries results in good visual outcome and prevention of complications like fibrous ingrowth and infection. PMID:26266144

  5. Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-?B Activation, and I?B? Degradation

    PubMed Central

    Qin, Shengnan; Ang, Estabelle; Dai, Libing; Yang, Xiaohong; Ye, Dongping; Chen, Honghui; Zhou, Lin; Yang, Mingli; Teguh, Dian; Tan, Renxiang; Xu, Jun; Tickner, Jennifer; Pavlos, Nathan J.; Xu, Jiake

    2015-01-01

    Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-?B and I?B? degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis. PMID:26556352

  6. Humanized Culture of Periosteal Progenitors in Allogeneic Serum Enhances Osteogenic Differentiation and In Vivo Bone Formation

    PubMed Central

    Owen, Helen C.; Tam, Wai Long; Solie, Lien; Van Cromphaut, Sophie J.; Van den Berghe, Greet; Luyten, Frank P.

    2014-01-01

    The translation of stem cell-based regenerative solutions from the laboratory to the clinic is often hindered by the culture conditions used to expand cell populations. Although fetal bovine serum (FBS) is widely used, regulatory bodies and safety concerns encourage alternative, xeno-free culturing practices. In an attempt to apply this approach to a bone-forming combination product of human periosteal progenitors (human periosteum derived cells) on a clinically used calcium phosphate carrier, FBS was substituted for human allogeneic serum (hAS) during cell expansion. It was found that cell proliferation was increased in hAS along with an apparent commitment to the osteogenic lineage, indicated by enhanced Runx2 expression, as well as alkaline phosphatase activity and matrix mineralization. Following analysis of signaling pathways, it was found that interferon-mediated signaling was downregulated, whereas JAK-STAT signaling was upregulated. STAT3 phosphorylation was enhanced in hAS-cultured human periosteum derived cells, inhibition of which ablated the proliferative effect of hAS. Furthermore, following in vivo implantation of hAS-cultured cells on NuOss scaffolds, enhanced bone formation was observed compared with FBS (71% increase, p < .001). Interestingly, the de novo-formed bone appeared to have a higher ratio of immature regions to mature regions, indicating that after 8 weeks implantation, tissue-formation processes were continuing. Integration of the implant with the environment appeared to be altered, with a decrease in calcium phosphate grain size and surface area, indicative of accelerated resorption. This study highlights the advantages of using humanized culture conditions for the expansion of human periosteal progenitors intended for bone regeneration. PMID:24375540

  7. Deletion of beta catenin in hypertrophic growth plate chondrocytes impairs trabecular bone formation.

    PubMed

    Golovchenko, Svitlana; Hattori, Takako; Hartmann, Christine; Gebhardt, Matthias; Gebhard, Sonja; Hess, Andreas; Pausch, Friederike; Schlund, Britta; von der Mark, Klaus

    2013-07-01

    In order to elucidate the role of ?-catenin in hypertrophic cartilage zone of the growth plate, we deleted the ?-catenin gene ctnnb1?specifically from hypertrophic chondrocytes by mating ctnnb1(fl/fl) mice with BAC-Col10a1-Cre-deleter mice. Surprisingly, this resulted in a significant reduction of subchondral trabecular bone formation in BACCol10Cre; ctnnb1(?/?) (referred to as Cat-ko) mice, although Cre expression was restricted to hypertrophic chondrocytes. The size of the Col10a1 positive hypertrophic zone was normal, but qRT-PCR revealed reduced expression of Mmp13, and Vegfa in Cat-ko hypertrophic chondrocytes, indicating impaired terminal differentiation. Immunohistological and in situ hybridization analysis revealed the substantial deficiency of collagen I positive mature osteoblasts, but equal levels of osterix-positive cells in the subchondral bone marrow space of Cat-ko mice, indicating that the supply of osteoblast precursor cells was not reduced. The fact that in Cat-ko mice subchondral trabeculae were lacking including their calcified cartilage core indicated a strongly enhanced osteoclast activity. In fact, TRAP staining as well as in situ hybridization analysis of Mmp9 expression revealed denser occupation of the cartilage erosion zone with enlarged osteoclasts as compared to the control growth plate, suggesting increased RANKL or reduced osteoprotegerin (Opg) activity in this zone. This notion was confirmed by qRT-PCR analysis of mRNA extracted from cultured hypertrophic chondrocytes or from whole epiphyses, showing increased Rankl mRNA levels in Cat-ko as compared to control chondrocytes, whereas changes in OPG levels were not significant. These results indicate that ?-catenin levels in hypertrophic chondrocytes play a key role in regulating osteoclast activity and trabecular bone formation at the cartilage-bone interface by controlling RANKL expression in hypertrophic chondrocytes. PMID:23567158

  8. Silorane resin supports proliferation, differentiation, and mineralization of MLO-A5 bone cells in vitro and bone formation in vivo

    PubMed Central

    Eick, J. David; Barragan-Adjemian, Cielo; Rosser, Jennifer; Melander, Jennifer R.; Dusevich, Vladimir; Weiler, Rachel A.; Miller, Bradley D.; Kilway, Kathleen V.; Dallas, Mark R.; Bi, Lianxing; Nalvarte, Elisabet L.; Bonewald, Lynda F.

    2015-01-01

    Methyl methacrylate used in bone cements has drawbacks of toxicity, high exotherm, and considerable shrinkage. A new resin, based on silorane/oxirane chemistry, has been shown to have little toxicity, low exotherm, and low shrinkage. We hypothesized that silorane-based resins may also be useful as components of bone cements as well as other bone applications and began testing on bone cell function in vitro and in vivo. MLO-A5, late osteoblast cells, were exposed to polymerized silorane (SilMix) resin (and a standard polymerized bisGMA/TEGDMA methacrylate (BT) resin and compared to culture wells without resins as control. A significant cytotoxic effect was observed with the BT resin resulting in no cell growth, whereas in contrast, SilMix resin had no toxic effects on MLO-A5 cell proliferation, differentiation, nor mineralization. The cells cultured with SilMix produced increasing amounts of alkaline phosphatase (1.8-fold) compared to control cultures. Compared to control cultures, an actual enhancement of mineralization was observed in the silorane resin-containing cultures at days 10 and 11 as determined by von Kossa (1.8–2.0 fold increase) and Alizarin red staining (1.8-fold increase). A normal bone calcium/phosphate atomic ratio was observed by elemental analysis along with normal collagen formation. When used in vivo to stabilize osteotomies, no inflammatory response was observed, and the bone continued to heal. In conclusion, the silorane resin, SilMix, was shown to not only be non cytototoxic, but actually supported bone cell function. Therefore, this resin has significant potential for the development of a nontoxic bone cement or bone stabilizer. PMID:22278990

  9. Silorane resin supports proliferation, differentiation, and mineralization of MLO-A5 bone cells in vitro and bone formation in vivo.

    PubMed

    Eick, J David; Barragan-Adjemian, Cielo; Rosser, Jennifer; Melander, Jennifer R; Dusevich, Vladimir; Weiler, Rachel A; Miller, Bradley D; Kilway, Kathleen V; Dallas, Mark R; Bi, Lianxing; Nalvarte, Elisabet L; Bonewald, Lynda F

    2012-04-01

    Methyl methacrylate used in bone cements has drawbacks of toxicity, high exotherm, and considerable shrinkage. A new resin, based on silorane/oxirane chemistry, has been shown to have little toxicity, low exotherm, and low shrinkage. We hypothesized that silorane-based resins may also be useful as components of bone cements as well as other bone applications and began testing on bone cell function in vitro and in vivo. MLO-A5, late osteoblast cells, were exposed to polymerized silorane (SilMix) resin (and a standard polymerized bisGMA/TEGDMA methacrylate (BT) resin and compared to culture wells without resins as control. A significant cytotoxic effect was observed with the BT resin resulting in no cell growth, whereas in contrast, SilMix resin had no toxic effects on MLO-A5 cell proliferation, differentiation, nor mineralization. The cells cultured with SilMix produced increasing amounts of alkaline phosphatase (1.8-fold) compared to control cultures. Compared to control cultures, an actual enhancement of mineralization was observed in the silorane resin-containing cultures at days 10 and 11 as determined by von Kossa (1.8-2.0 fold increase) and Alizarin red staining (1.8-fold increase). A normal bone calcium/phosphate atomic ratio was observed by elemental analysis along with normal collagen formation. When used in vivo to stabilize osteotomies, no inflammatory response was observed, and the bone continued to heal. In conclusion, the silorane resin, SilMix, was shown to not only be non cytototoxic, but actually supported bone cell function. Therefore, this resin has significant potential for the development of a nontoxic bone cement or bone stabilizer. PMID:22278990

  10. Investigation on stability of directionally solidified CBr4 C2Cl6 lamellar eutectic by using multiphase field simulation

    NASA Astrophysics Data System (ADS)

    Zhu, Yao-Chan; Wang, Jin-Cheng; Yang, Gen-Cang; Zhao, Da-Wen

    2007-03-01

    With the multiphase field method, the stability of lamellar basic state is investigated during the directional solidification of eutectic alloy CBr4-C2Cl6. A great number of lamellar patterns observed in experiments are simulated, and a stability diagram for lamellar pattern selections is presented. The simulated growth behaviours of these patterns are found to be qualitatively consistent with Karma et al's numerical calculations and experimental results. The formation of the primary instability is attributed to the destabilization of solute boundary layer.

  11. The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Wronski, T. J.; GLOBUS. R.; Levens, M. J.; Morey-Holton, E.

    1983-01-01

    Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus (P sub i), 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D (24,25(OH)2D and 1,25-dihydroxyvitamin D (1,25(OH)2D. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P 0.01), a 32% decrease in bone surface lined with osteoblasts (P .05), no change in bone surface lined with osteoclasts and a decrease in circulating (1,25(OH)2D. No significant changes in the serum concentrations of P sub i, 25-OH-D or 24,25(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control and serum Ca and 1,25(OH)2D returned to control values. Maintenance of a constant serum 1,25(OH)2D concentration by chronic infusion of 1,25(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation which in turn produces a transitory hypercalcemia.

  12. Prednisolone alone, or in combination with estrogen or dietary calcium deficiency or immobilization, inhibits bone formation but does not induce bone loss in mature rats.

    PubMed

    Shen, V; Birchman, R; Liang, X G; Wu, D D; Lindsay, R; Dempster, D W

    1997-10-01

    Glucocorticoid use has long been recognized as a risk factor for bone loss, resulting in an increased fracture incidence in humans. However, steroid-treated patients often present with other complications that predispose to bone loss, such as immobilization, and little is known about the interaction of these other risk factors for bone loss and glucocorticoids. In the present study, mature female rats were treated with prednisolone (Pred) or vehicle, in combination with ovariectomy (ovx), dietary calcium deficiency (LoCa), or right hind limb immobilization (IM). After 4 weeks of treatment, the rats were killed and the right tibia and tibiofibular junction were collected for quantitative histomorphometric analysis and the right femur was collected for bone mineral density (BMD) and mechanical strength determinations. As expected, ovx, LoCa, and IM decreased BMD in the distal femur and cancellous bone volume (CnBV/TV) in the proximal tibia. All Pred-treated groups responded with increases of BMD and CnBV/TV, when compared to their respective non-Pred treated groups. Mechanical strength testing of the cancellous bone of the distal femur reflected the changes in BMD and CnBV/TV. No differences in trabecular plate thickness were noted in any of the treatment groups. The Pred group showed a significant reduction in longitudinal growth rate, as well as bone formation rate (BFR/BS), in the proximal tibia when compared with their respective control groups, the latter indicated by a decrease in both mineralizing surface and mineral apposition rate. Most notably, osteoclast surface and urinary free pyridinoline, a bone resorption marker, increased significantly with each of the three risk factors. Pred treatment inhibited these increases but it did not exert significant reductions when used by itself. At the tibiofibular junction, there were no measurable changes in either total bone or cortical bone area. Endocortical BFR/BS were increased by ovx or LoCa but each was lowered by Pred treatment. Periosteal BFR/BS were increased by ovx and IM, and Pred exerted significant inhibition by itself and in combination with other risk factors. We conclude, therefore, that unlike the effects observed in humans treated with glucocorticoid, treatment of rats with prednisolone not only does not result in bone loss but may exert a protective effect on the skeleton through the inhibition of bone resorption. PMID:9315338

  13. Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice.

    PubMed Central

    Kitazawa, R; Kimble, R B; Vannice, J L; Kung, V T; Pacifici, R

    1994-01-01

    To investigate the contribution of IL-1, IL-6, and TNF to the increased osteoclastogenesis induced by estrogen deficiency, ovariectomized (ovx) mice were treated with either IL-1 receptor antagonist (IL-1ra), a competitive inhibitor of IL-1, TNF binding protein (TNFbp), an inhibitor of TNF, or the anti-IL-6 antibody (Ab) 20F3 for the first 2 wk after surgery. ovx increased the bone marrow cells secretion of IL-1 and TNF, but not IL-6, and the formation of TRAP-positive osteoclast-like multinucleated cells (MNCs) in bone marrow cultures treated with 1,25(OH)2D3. The increase in MNC formation induced by ovx was prevented by in vivo treatment with either 17 beta estradiol, IL-1ra, TNFbp, or anti-IL-6 Ab. However, the percent change in MNC formation induced by the anti-IL-6 Ab was similar in ovx and sham-operated animals, whereas IL-1ra and TNFbp were effective only in ovx mice. MNC formation was also decreased by in vitro treatment of bone marrow cultures with IL-1ra and TNFbp, but not with anti-IL-6 Ab. Ovx also increased bone resorption in vivo and in vitro, as assessed by the urinary excretion of pyridinoline cross links and the formation of resorption pits, respectively. IL-1ra, TNFbp and estrogen decreased bone resorption in vivo and in vitro whereas the anti-IL-6 Ab inhibited bone resorption in vitro but not in vivo. In conclusion, these data indicate that IL-1 and TNF play a direct role in mediating the effects of ovx on osteoclastogenesis and bone resorption. The data also suggest that IL-6 is not essential for increasing bone resorption in the early postovariectomy period. Images PMID:7989596

  14. Ethanolic extract of Actaea racemosa (black cohosh) potentiates bone nodule formation in MC3T3-E1 preosteoblast cells.

    PubMed

    Chan, B Y; Lau, K S; Jiang, B; Kennelly, E J; Kronenberg, F; Kung, A W C

    2008-09-01

    Aceaea racemosa (formerly Cimicifuga racemosa, black cohosh, AR) extracts have been widely used as an alternative to hormonal replacement therapy for menopausal symptoms. Recent evidences suggest AR extracts are also effective in protecting against postmenopausal bone loss. To determine whether AR has any direct anabolic effect on osteoblasts, we investigated the ethanolic extract of AR on bone nodule formation in mouse MC3T3-E1 preosteoblast cells. AR did not stimulate osteoblast proliferation. Rather, at high doses of 1000 ng/mL for 48 h, AR suppressed (7.2+/-0.9% vs. control) osteoblast proliferation. At 500 ng/mL, a significant increase in bone nodule formation was seen with Von Kossa staining. Using quantitative PCR analysis, AR was shown to enhance the gene expression of runx2 and osteocalcin. Co-treatment with ICI 182,780, the selective estrogen receptor antagonist, abolished the stimulatory effect of AR on runx2 and osteocalcin gene induction, as well as on bone nodule formation in MC3T3-E1 cells. This is a first report of the direct effect of AR on enhancement of bone nodule formation in osteoblasts, and this action was mediated via an estrogen receptor-dependent mechanism. The results provide a scientific rationale at the molecular level for the claim that AR can offer effective prevention of postmenopausal bone loss. PMID:18555764

  15. Loss of Prostaglandin E2-induced Extra Cortical Bone after its Withdrawal in Rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1992-01-01

    The object of this study was to determine the fate of PGE2-induced new cortical bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3 and 6 mg PGE2/kg/day for 60 days and then withdrawn for 60 and 120 days (on/off treatment). Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). In a previous report we showed that after 60, 120 and 180 days of daily PGE2 (on)treatment, a new steady state was achieved marked by increased total bone area (+ 16%, +25% and + 34% with 1, 3 and 6 mg PGE2/kg/day) when compared to age-matched controls. The continuous PGE2 treatment stimulated periosteal and endocortical lamellar bone formation, activated endocortical woven trabecular bone formation and intracortical bone resorption. These responses increased cortical bone mass since the bone formation exceeded bone resorption. The current study showed that after withdrawal of PGE2 for 60 and 120 days, the extra endocortical bone, which was induced by the first 60-days treatment, was resorbed, but the new subperiosteal bone persisted resulting in a tibial shaft with larger cross sectional and marrow areas. Despite that, there was still the same amount of bone mass in these shafts as in age-related controls. A new steady state was achieved after 60 days of withdrawal, in which the bone mass and bone formation activity approximated that of age-related controls. It was concluded that maintaining the extra PGE2-induced cortical bone mass depends on continuous daily administration of PGE2.

  16. Loss of Prostaglandin E2-induced Extra Cortical Bone After its Withdrawal in Rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1992-01-01

    The object of this study was to determine the fate of PGE2-(Prostaglandin E2) induced new cortical bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3 and 6 mg PGE2/kg/day for 60 days and then withdrawn for 60 and 120 days (on/off treatment). Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). In a previous report we showed that after 60, 120 and 180 days of daily PGE2 (on)treatment, a new steady state was achieved marked by increased total bone area (+16%, +25% and +34% with 1, 3 and 6 mg PGE2/kg/day) when compared to age-matched controls. The continuous PGE2 treatment stimulated periosteal and endocortical lamellar bone formation, activated endocortical woven trabecular bone formation and intracortical bone resorption. These responses increased cortical bone mass since the bone formation exceeded bone resorption. The current study showed that after withdrawal of PGE2 for 60 and 120 days, the extra endocortical bone, which was induced by the first 60-days treatment, was resorbed, but the new subperiosteal bone persisted resulting in a tibial shaft with larger cross sectional and marrow areas. Despite that, there was still the same amount of bone mass in these shafts as in age-related controls. A new steady state was achieved after 60 days of withdrawal, in which the bone mass and bone formation activity approximated that of age-related controls. It was concluded that maintaining the extra PGE2-induced cortical bone mass depends on continuous daily administration of PGE2.

  17. Using poly(lactic-co-glycolic acid) microspheres to encapsulate plasmid of bone morphogenetic protein 2/polyethylenimine nanoparticles to promote bone formation in vitro and in vivo

    PubMed Central

    Qiao, Chunyan; Zhang, Kai; Jin, Han; Miao, Leiying; Shi, Ce; Liu, Xia; Yuan, Anliang; Liu, Jinzhong; Li, Daowei; Zheng, Changyu; Zhang, Guirong; Li, Xiangwei; Yang, Bai; Sun, Hongchen

    2013-01-01

    Repair of large bone defects is a major challenge, requiring sustained stimulation to continually promote bone formation locally. Bone morphogenetic protein 2 (BMP-2) plays an important role in bone development. In an attempt to overcome this difficulty of bone repair, we created a delivery system to slowly release human BMP-2 cDNA plasmid locally, efficiently transfecting local target cells and secreting functional human BMP-2 protein. For transfection, we used polyethylenimine (PEI) to create pBMP-2/PEI nanoparticles, and to ensure slow release we used poly(lactic-co-glycolic acid) (PLGA) to create microsphere encapsulated pBMP-2/PEI nanoparticles, PLGA@pBMP-2/PEI. We demonstrated that pBMP-2/PEI nanoparticles could slowly release from the PLGA@pBMP-2/PEI microspheres for a long period of time. The 3–15 ?m diameter of the PLGA@pBMP-2/PEI further supported this slow release ability of the PLGA@pBMP-2/PEI. In vitro transfection assays demonstrated that pBMP-2/PEI released from PLGA@pBMP-2/PEI could efficiently transfect MC3T3-E1 cells, causing MC3T3-E1 cells to secrete human BMP-2 protein, increase calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7 and I type collagen (COLL I), and finally induce MC3T3-E1 cell differentiation. Importantly, in vivo data from micro-computed tomography (micro-CT) and histological staining demonstrated that the human BMP-2 released from PLGA@pBMP-2/PEI had a long-term effect locally and efficiently promoted bone formation in the bone defect area compared to control animals. All our data suggest that our PLGA-nanoparticle delivery system efficiently and functionally delivers the human BMP-2 cDNA and has potential clinical application in the future after further modification. PMID:23990717

  18. Sustained Modeling-Based Bone Formation During Adulthood in Cynomolgus Monkeys May Contribute to Continuous BMD Gains With Denosumab.

    PubMed

    Ominsky, Michael S; Libanati, Cesar; Niu, Qing-Tian; Boyce, Rogely W; Kostenuik, Paul J; Wagman, Rachel B; Baron, Roland; Dempster, David W

    2015-07-01

    Denosumab (DMAb) administration to postmenopausal women with osteoporosis is associated with continued bone mineral density (BMD) increases and low fracture incidence through 8 years, despite persistently reduced bone turnover markers and limited fluorochrome labeling in iliac crest bone biopsies. BMD increases were hypothesized to result from additional accrual of bone matrix via modeling-based bone formation-a hypothesis that was tested by examining fluorochrome labeling patterns in sections from ovariectomized (OVX) cynomolgus monkeys (cynos) treated with DMAb for 16 months. Mature OVX or Sham cynos were treated monthly with vehicle for 16 months, whereas other OVX cynos received monthly 25 or 50?mg/kg DMAb. DMAb groups exhibited very low serum bone resorption and formation biomarkers and near-absent fluorochrome labeling in proximal femur cancellous bone. Despite these reductions, femoral neck dual-energy X-ray absorptiometry (DXA) BMD continued to rise in DMAb-treated cynos, from a 4.6% increase at month 6 to 9.8% above baseline at month 16. Further examination of cortical bone in the proximal femur demonstrated consistent and prominent labeling on the superior endocortex and the inferior periosteal surface, typically containing multiple superimposed labels from month 6 to 16 over smooth cement lines, consistent with continuous modeling-based bone formation. These findings were evident in all groups. Quantitative analysis at another modeling site, the ninth rib, demonstrated that DMAb did not alter the surface extent of modeling-based labels, or the cortical area bound by them, relative to OVX controls, while significantly reducing remodeling-based bone formation and eroded surface. This conservation of modeling-based formation occurred concomitantly with increased femoral neck strength and, when coupled with a reduction in remodeling-based bone loss, is likely to contribute to increases in bone mass with DMAb treatment. Thus, this study provides preclinical evidence for a potential mechanism that could contribute to the clinical observations of continued BMD increases and low fracture rates with long-term DMAb administration. PMID:25684625

  19. Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation.

    PubMed

    Honda, Yoshitomo; Tanaka, Tomonari; Tokuda, Tomoko; Kashiwagi, Takahiro; Kaida, Koji; Hieda, Ayato; Umezaki, Yasuyuki; Hashimoto, Yoshiya; Imai, Koichi; Matsumoto, Naoyuki; Baba, Shunsuke; Shimizutani, Kimishige

    2015-01-01

    Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy. PMID:26110386

  20. Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation

    PubMed Central

    Honda, Yoshitomo; Tanaka, Tomonari; Tokuda, Tomoko; Kashiwagi, Takahiro; Kaida, Koji; Hieda, Ayato; Umezaki, Yasuyuki; Hashimoto, Yoshiya; Imai, Koichi; Matsumoto, Naoyuki; Baba, Shunsuke; Shimizutani, Kimishige

    2015-01-01

    Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel) prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-morpholinium chloride (DMT-MM) gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells) within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy. PMID:26110386

  1. Dual Delivery of EPO and BMP2 from a Novel Modular Poly-?-Caprolactone Construct to Increase the Bone Formation in Prefabricated Bone Flaps.

    PubMed

    Patel, Janki Jayesh; Modes, Jane E; Flanagan, Colleen L; Krebsbach, Paul H; Edwards, Sean P; Hollister, Scott J

    2015-09-01

    Poly-?-caprolactone (PCL) is a biocompatible polymer that has mechanical properties suitable for bone tissue engineering; however, it must be integrated with biologics to stimulate bone formation. Bone morphogenetic protein-2 (BMP2) delivered from PCL produces bone when implanted subcutaneously, and erythropoietin (EPO) works synergistically with BMP2. In this study, EPO and BMP2 are adsorbed separately on two 3D-printed PCL scaffold modules that are assembled for codelivery on a single scaffold structure. This assembled modular PCL scaffold with dual BMP2 and EPO delivery was shown to increase bone growth in an ectopic location when compared with BMP2 delivery along a replicate scaffold structure. EPO (200?IU/mL) and BMP2 (65??g/mL) were adsorbed onto the outer and inner portions of a modular scaffold, respectively. Protein binding and release studies were first quantified. Subsequently, EPO+BMP2 and BMP2 scaffolds were implanted subcutaneously in mice for 4 and 8 weeks, and the regenerated bone was analyzed with microcomputed tomography and histology; 8.6±1.4??g BMP2 (22%) and 140±29?IU EPO (69.8%) bound to the scaffold and <1% BMP2 and 83% EPO was released in 7 days. Increased endothelial cell proliferation on EPO-adsorbed PCL discs indicated protein bioactivity. At 4 and 8 weeks, dual BMP2 and EPO delivery regenerated more bone (5.1±1.1 and 5.5±1.6?mm(3)) than BMP2 alone (3.8±1.1 and 4.3±1.7?mm(3)). BMP2 and EPO scaffolds had more ingrowth (1.4%±0.6%) in the outer module when compared with BMP2 (0.8%±0.3%) at 4 weeks. Dual delivery produced more dense cellular marrow, while BMP2 had more fatty marrow. Dual EPO and BMP2 delivery is a potential method to regenerate bone faster for prefabricated flaps. PMID:25809081

  2. Relative bone mass decreased in mice fed high dietary fat despite an increase in body mass and bone formation markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Osteoporosis and obesity are interrelated health disorders. Osteoblasts and adipocytes are derived from common mesenchymal stem cells and age-related osteoporosis is associated with increased bone marrow adipogenesis. To determine whether bone mass and osteoblast number and activity are affected by ...

  3. Low-level laser therapy improves bone formation: stereology findings for osteoporosis in rat model.

    PubMed

    Scalize, Priscilla Hakime; de Sousa, Luiz Gustavo; Regalo, Simone Cecílio Hallak; Semprini, Marisa; Pitol, Dimitrius Leonardo; da Silva, Giselle Aparecida; de Almeida Coelho, Jéssica; Coppi, Antônio Augusto; Laad, Aliny A B Lobo; Prado, Karina Fittipaldi Bombonato; Siessere, Selma

    2015-07-01

    Low-level laser therapy (LLLT) benefits bone metabolism, but its use needs to be standardized. We evaluated the effects of LLLT on bone defects in calvaria of ovariectomized rats. Stereology was used to calculate tissue repair volume (V tr ), density of trabecular bone volume (Vv t ), total volume of newly formed trabecular bone (Vtot), and the area occupied by collagen fibers (A C ). Fifty-four Wistar rats were submitted to bilateral ovariectomy, and bone defects were created in calvaria after 150 days. The animals were divided into nine groups (n?=?6), and 24 h after defects, the treatment started with a 780-nm low-intensity GaAlAs laser: G1, G2, and G3 received 3 sessions of 0, 20, and 30 J/cm(2) respectively; G4, G5, and G6 received 6 sessions of 0, 20, and 30 J/cm(2), respectively; and G7, G8, and G9 received 12 sessions of 0, 20, and 30 J/cm(2), respectively. A normal distribution was found for all of the data. The test used to verify the normality was the Kolmogorov-Smirnov (KS, p?>?0.05). The one-way ANOVA followed by Tukey's post hoc test was used for data processing. A difference of p?bone formation in the groups that received 20 and 30 J/cm(2) when compared to control groups, but over time, the dose of 30 J/cm(2) showed better stereological parameters when compared to 20 J/cm(2). PMID:26037661

  4. Heat and Radiofrequency Plasma Glow Discharge Pretreatment of a Titanium Alloy Promote Bone Formation and Osseointegration

    PubMed Central

    MacDonald, Daniel E.; Rapuano, Bruce E.; Vyas, Parth; Lane, Joseph M.; Meyers, Kathleen; Wright, Timothy

    2013-01-01

    Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600°C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1 nM) or left uncoated and surgically implanted into the rat femoral medullary cavity. Animals were euthanized 3 or 6 weeks later, and femurs were removed for analysis. The number of trabeculae in contact with the implant surface, surface contact between trabeculae and the implant, and the length and area of bone attached to the implant were measured by histomorphometry. Implant shear strength was measured by a pull-out test. Both pretreatments and fibronectin enhanced the number of trabeculae bonding with the implant and trabeculae-to-implant surface contact, with greater effects of fibronectin observed with pretreated compared to untreated implants. RFGD pretreatment modestly increased implant shear strength, which was highly correlated (r2 = 0.87 – 0.99) with measures of trabecular bonding for untreated and RFGD-pretreated implants. In contrast, heat pretreatment increased shear strength 3 to 5-fold for both uncoated and fibronectin-coated implants at 3 and 6 weeks, suggesting a more rapid increase in implant-femur bonding compared to the other groups. In summary, our findings suggest that the heat and RFGD pretreatments can promote the osseointegration of a titanium alloy implant material. PMID:23649564

  5. Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone formation and implant fixation in sheep.

    PubMed

    Ding, Ming; Andreasen, Christina M; Dencker, Mads L; Jensen, Anders E; Theilgaard, Naseem; Overgaard, Søren

    2015-04-01

    Cylindrical critical size defects were created at the distal femoral condyles bilaterally of eight female adult sheep. Titanium implants with 2-mm concentric gaps were inserted and the gaps were filled with one of the four materials: allograft; a synthetic 15-amino acid cell-binding peptide coated hydroxyapatite (ABM/P-15); hydroxyapatite + ?tricalciumphosphate+ Poly-Lactic-Acid (HA/?TCP-PDLLA); or ABM/P-15+HA/?TCP-PDLLA. After nine weeks, bone-implant blocks were harvested and sectioned for micro-CT scanning, push-out test, and histomorphometry. Significant bone formation and implant fixation could be observed in all four groups. Interestingly, the microarchitecture of the ABM/P-15 group was significantly different from the control group. Tissue volume fraction and thickness were significantly greater in the ABM/P-15 group than in the allograft group. Bone formation and bone ingrowth to porous titanium implant were not significantly different among the four groups. The ABM/P-15 group had similar shear mechanical properties on implant fixation as the allograft group. Adding HA/?TCP-PDLLA to ABM/P-15 did not significantly change these parameters. This study revealed that ABM/P-15 had significantly bone formation in concentric gap, and its enhancements on bone formation and implant fixation were at least as good as allograft. It is suggested that ABM/P-15 might be a good alternative biomaterial for bone implant fixation in this well-validated critical-size defect gap model in sheep. Nevertheless, future clinical researches should focus on prospective, randomized, controlled trials in order to fully elucidate whether ABM/P-15 could be a feasible candidate for bone substitute material in orthopedic practices. PMID:25045068

  6. Multiwalled carbon nanotubes enhance electrochemical properties of titanium to determine in situ bone formation

    NASA Astrophysics Data System (ADS)

    Sirivisoot, Sirinrath; Webster, Thomas J.

    2008-07-01

    Multiwalled carbon nanotubes (MWCNTs) enhance osteoblast (bone-forming cell) calcium deposition compared to currently implanted materials (such as titanium). In this study, MWCNTs were grown out of nanopores anodized on titanium (MWCNT-Ti). The electrochemical responses of MWCNT-Ti were investigated in an attempt to ascertain if MWCNT-Ti can serve as novel in situ sensors of bone formation. For this purpose, MWCNT-Ti was subjected to a ferri/ferrocyanide redox couple and its electrochemical behavior measured. Cyclic voltammograms (CVs) showed an enhanced redox potential for the MWCNT-Ti. These redox signals were superior to that obtained with bare unmodified Ti, which did not sense either oxidation or reduction peaks in the CVs. A further objective of this study was to investigate the redox reactions of MWCNT-Ti in a solution of extracellular components secreted by osteoblasts in vitro. It was found that MWCNT-Ti exhibited well-defined and persistent CVs, similar to the ferri/ferrocyanide redox reaction. The higher electrodic performance and electrocatalytic activity of the MWCNT-Ti compared to the bare titanium observed in this study were likely due to the fact that MWCNTs enhanced direct electron transfer and facilitated double-layer effects, leading to a strong redox signal. Thus these results encourage the further study and modification of MWCNT-Ti to sense new bone growth in situ next to orthopedic implants and perhaps monitor other events (such as infection and/or harmful scar tissue formation) to improve the current clinical diagnosis of orthopedic implants.

  7. Evaluating apatite formation and osteogenic activity of electrospun composites for bone tissue engineering.

    PubMed

    Patlolla, Ajitha; Arinzeh, Treena Livingston

    2014-05-01

    Significant interest has been in examining calcium phosphate ceramics, specifically ?-tricalcium phosphate (?-TCP) (Ca3 (PO4)2 ) and synthetic hydroxyapatite (HA) (Ca10 (PO4)6 (OH)2 ), in composites and more recently, in fibrous composites formed using the electrospinning technique for bone tissue engineering applications. Calcium phosphate ceramics are sought because they can be bone bioactive, which means an apatite forms on their surface that facilitates bonding to bone tissue, and are osteoconductive. However, studies examining the bioactivity of electrospun composites containing calcium phosphates and their corresponding osteogenic activity have been limited. In this study, electrospun composites consisting of (20/80) HA/TCP nanoceramics and poly (?-caprolactone) (PCL) were fabricated. Solvent and solvent combinations were evaluated to form scaffolds with a maximum concentration and dispersion of ceramic and pore sizes large enough for cell infiltration and tissue growth. PCL was dissolved in either methylene chloride (Composite-MC) or a combination of methylene chloride (80%) and dimethylformamide (20%; Composite-MC?+?DMF). Composites were evaluated in vitro for degradation, apatite formation, and osteogenic differentiation of human mesenchymal stem cells (MSCs) with an emphasis on temporal gene expression of osteogenic markers and the pluripotent gene Sox-2. Apatite formation and the osteogenic differentiation was the greatest for Composite-MC as determined by gene expression, protein production and biochemical markers, even without the presence of osteoinductive factors in the media, in comparison to Composite-MC?+?DMF and unfilled PCL mats. Sox-2 levels also reduced over time. The results of this study demonstrate that the solvent or solvent combination used in preparing the electrospun composite mats plays a critical role in determining their bioactivity which may, in turn, affect cell behavior. PMID:24264603

  8. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation.

    PubMed

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T; Darnell, Max C; Desai, Rajiv M; Madl, Christopher M; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E; Duda, Georg N; Mooney, David J

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel's elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel's elasticity regulated bone regeneration, with optimal bone formation at 60?kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ. PMID:26366848

  9. Evolution of density fluctuations to lamellar crystals in linear polyethylene

    SciTech Connect

    Akpalu, Y.A.; Amis, E.J.

    1999-11-01

    Structure formation during the isothermal crystallization of a linear polyethylene (M{sub w}=32&hthinsp;100 g/mol, M{sub w}/M{sub n}=1.1) has been monitored by simultaneous real time small-angle x-ray scattering (SAXS) and wide angle x-ray scattering (WAXS) with synchrotron radiation. Changes in the crystalline and amorphous scattering in WAXS occur simultaneously with the changes observed in the SAXS intensity profile, suggesting that the resulting scattering is a consequence of forming crystals. At the early stage of crystal growth, the SAXS intensity at q{lt}0.02&hthinsp;{Angstrom}{sup {minus}1} increases while that at higher wave vectors remains constant. Meanwhile, the apparent crystallinity from WAXS increases to about 10{percent} before two peaks in the SAXS intensity profile can be resolved. As lamellar stacks develop, the period corresponding to the first SAXS peak, L{sub 1}, decreases initially. After reaching a minimum, L{sub 1} further increases with crystallization time. On the other hand, the period corresponding to the second SAXS peak increases with crystallization time. At late times, the rate of increase is very slow. Changes in the crystallinity obtained from WAXS and the total scattering power from SAXS were evaluated and compared with a model for the crystallizing system which accounts for changes in the fraction of lamellar aggregates. The relative importance of two secondary crystallization processes, namely the formation of new lamellar stacks and increase in the crystallinity within lamellae, were evaluated during and after primary crystallization. {copyright} {ital 1999 American Institute of Physics.}

  10. Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

    PubMed Central

    2013-01-01

    Background Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods One gram each of either a porous beta-tricalcium phosphate (?-TCP) or an hydroxyapatite/silicon dioxide (HA/SiO2)-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting. PMID:23286366

  11. Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Sakhaee, K.; Breslau, N. A.; Gottschalk, F.; Pak, C. Y.

    1992-01-01

    We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24-hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/- 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/- 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS).

  12. Ultrafiltration of equine digital lamellar tissue.

    PubMed

    Underwood, Claire; Collins, Simon N; van Eps, Andrew W; Allavena, Rachel E; Medina-Torres, Carlos E; Pollitt, Christopher C

    2014-11-01

    There are no experimentally validated pharmacological means of preventing laminitis; however, locally acting pharmaceutical agents with the potential to prevent laminitis have been identified. Demonstrating therapeutic drug concentrations in lamellar tissue is essential for evaluating the efficacy of these agents. The aim of this study was to develop an experimental technique for repeatedly sampling lamellar interstitial fluid. A technique for placing ultrafiltration probes was developed in vitro using 15 cadaver limbs. Subsequently, lamellar ultrafiltration probes were placed in one forelimb in six living horses. Interstitial fluid was collected continuously from the probes as ultrafiltrate for 4 (n?=?4) or 14?days (n?=?2). The rate of ultrafiltrate collection was calculated every 12?h. Biochemical analyses were performed on ultrafiltrate collected on night 1 (12-24?h post-implantation) and night 4 (84-96?h post-implantation). Sections surrounding the probe and control tissue from the contralateral limb were harvested, stained with H&E and Masson's trichrome and scored based on the tissue response to the probe. Ultrafiltration probes were placed in the lamellar tissue in all six horses. Ultrafiltrate was collected from these probes at 55 (30-63)??L/h (median [interquartile range]). Fluid production decreased significantly with time from night 3 onwards (P??0.05). The technique was well tolerated. This study demonstrates that ultrafiltration can be used to sample equine digital lamellar interstitial fluid, and has potential for measuring lamellar drug levels. PMID:25439438

  13. Slow dynamics of a colloidal lamellar phase

    E-print Network

    Doru Constantin; Patrick Davidson; Éric Freyssingeas; Anders Madsen

    2015-04-06

    We used x-ray photon correlation spectroscopy to study the dynamics in the lamellar phase of a platelet suspension as a function of the particle concentration. We measured the collective diffusion coefficient along the director of the phase, over length scales down to the interparticle distance, and quantified the hydrodynamic interaction between the particles. This interaction sets in with increasing concentration and can be described qualitatively by a simplified model. No change in the microscopic structure or dynamics is observed at the transition between the fluid and the gel-like lamellar phases.

  14. Microstructure and Texture Evolution during Friction Stir Processing of Fully Lamellar Ti-6Al-4V

    NASA Astrophysics Data System (ADS)

    Pilchak, A. L.; Williams, J. C.

    2011-03-01

    Friction stir processing (FSP) was used to locally refine a thin surface layer of the coarse, fully lamellar microstructure of investment-cast Ti-6Al-4V. Depending on the peak temperature reached in the stir zone during processing relative to the ? transus, three distinct classes of microstructures were observed. Using accepted wrought product terminology, they are equiaxed, bimodal, and lamellar, except for the case of FSP, the length scale of each was smaller by at least an order of magnitude compared to typical wrought material. The evolution of an initially strain-free fully lamellar microstructure to each of these three refined conditions was characterized with scanning electron microscopy, transmission electron microscopy and electron backscatter diffraction. The fundamental mechanisms underlying grain refinement during FSP, including both the morphological changes and the formation of high-angle grain boundaries, were discussed.

  15. Ameloblastin expression and putative autoregulation in mesenchymal cells suggest a role in early bone formation and repair

    PubMed Central

    Tamburstuen, Margareth V.; Reseland, Janne E.; Spahr, Axel; Brookes, Steven J.; Kvalheim, Gunnar; Slaby, Ivan; Snead, Malcolm L.; Lyngstadaas, S. Petter

    2015-01-01

    Ameloblastin is mainly known as a dental enamel protein, synthesized and secreted into developing enamel matrix by the enamel-forming ameloblasts. The function of ameloblastin in tooth development remains unclear, but it has been suggested to be involved in processes varying from regulating crystal growth to activity as a growth factor or partaking in cell signaling. Recent studies suggest that some enamel matrix proteins also might have important functions outside enamel formation. In this context ameloblastin has recently been reported to induce dentin and bone repair, as well as being present in the early bone and cartilage extracellular matrices during embryogenesis. However, what cells express ameloblastin in these tissues still remain unclear. Thus, the expression of ameloblastin was examined in cultured primary mesenchymal cells and in vivo during healing of bone defects in a “proof of concept” animal study. The real time RT-PCR analysis revealed human ameloblastin (AMBN) mRNA expression in human mesenchymal stem cells and primary osteoblasts and chondrocytes. Expression of AMBN mRNA was also confirmed in human CD34 positive cells and osteoclasts. Western and dot blot analysis of cell lysates and medium confirmed the expression and secretion of ameloblastin from mesenchymal stem cells, primary human osteoblasts and chondrocytes. Expression of ameloblastin was also detected in newly formed bone in experimental bone defects in adult rats. Together these findings suggest a role of this protein in early bone formation and repair. PMID:20854943

  16. Spectroscopic investigation on formation and growth of mineralized nanohydroxyapatite for bone tissue engineering applications

    NASA Astrophysics Data System (ADS)

    Gopi, D.; Nithiya, S.; Shinyjoy, E.; Kavitha, L.

    Synthetic calcium hydroxyapatite (HAP,Ca10(PO4)6(OH)2) is a well-known bioceramic material used in orthopaedic and dental applications because of its excellent biocompatibility and bone-bonding ability. Substitution of trace elements, such as Sr, Mg and Zn ions into the structure of calcium phosphates is the subject of widespread investigation. In this paper, we have reported the synthesis of Sr, Mg and Zn co-substituted nanohydroxyapatite by soft solution freezing method. The effect of pH on the morphology of bioceramic nanomaterial was also discussed. The in vitro bioactivity of the as-synthesized bioceramic nanomaterial was determined by soaking it in SBF for various days. The as-synthesized bioceramic nanomaterial was characterized by Fourier transform infrared spectroscopy, X- ray diffraction analysis, Scanning electron microscopy and Energy dispersive X-ray analysis and Transmission electron microscopic techniques respectively. The results obtained in our study have revealed that pH 10 was identified to induce the formation of mineralized nanohydroxyapatite. It is observed that the synthesis of bioceramic nanomaterial not only support the growth of apatite layer on its surface but also accelerate the growth which is evident from the in vitro studies. Therefore, mineralized nanohydroxyapatite is a potential candidate in bone tissue engineering.

  17. Calcium Plasma Implanted Titanium Surface with Hierarchical Microstructure for Improving the Bone Formation.

    PubMed

    Cheng, Mengqi; Qiao, Yuqin; Wang, Qi; Jin, Guodong; Qin, Hui; Zhao, Yaochao; Peng, Xiaochun; Zhang, Xianlong; Liu, Xuanyong

    2015-06-17

    Introducing hierarchical microstructure and bioactive trace elements simultaneously onto the surface of titanium implant is a very effective way to improve the osseointegration between bone and implant. In this work, hierarchical topography was prepared on Ti surface via acid etching and sandblasting (SLA) to form micropits and microcavities then underwent Ca plasma immersion ion implantation (Ca-PIII) process. The surface wettability and roughness did not change obviously before and after Ca-PIII process. The in vitro evaluations including cell adhesion, activity, alkaline phosphatase (ALP), osteogenic genes (Runx2, OSX, ALP, BSP, Col1a1, OPN, and OC), and protein (BSP, Col1a1, OPN, and OC) expressions revealed that the introduction of Ca ions onto the surface of SLA-treated Ti can promote greater osteoblasts adhesion, spread and proliferation, which in return further accelerated the maturation and mineralization of osteoblasts. More importantly, in vivo evaluations including Micro-CT evaluation, histological observations, push-out test, sequential fluorescent labeling and histological observations verified that Ca-SLA-treated Ti implants could efficiently promote new bone formation in early times. These promising results suggest that Ca-SLA-treated Ti has the potential for future application in orthopedic field. PMID:26020570

  18. Myristoleic acid inhibits osteoclast formation and bone resorption by suppressing the RANKL activation of Src and Pyk2.

    PubMed

    Kwon, Jun-Oh; Jin, Won Jong; Kim, Bongjun; Kim, Hong-Hee; Lee, Zang Hee

    2015-12-01

    Cytoskeletal changes in osteoclasts such as formation of actin ring is required for bone-resorbing activity. The tyrosine kinase Src is a key player in massive cytoskeletal change of osteoclasts, thereby in bone destruction. In order for Src to be activated, trafficking to the inner plasma membrane via myristoylation is of importance. A previous study reported that myristoleic acid derived from myristic acid, inhibited N-myristoyl-transferase, an essential enzyme for myristoylation process. This prompted us to investigate whether myristoleic acid could affect osteoclastogenesis. Indeed, we observed that myristoleic acid inhibited RANKL-induced osteoclast formation in vitro, especially, at later stages of differentiation. Myristoleic acid attenuated the tyrosine phosphorylation of c-Src and Pyk2, which associates with Src, by RANKL. When myristoleic acid was co-administered with soluble RANKL into mice, RANKL-induced bone loss was substantially prevented. Bone dissection clearly revealed that the number of multinucleated osteoclasts was significantly diminished by myristoleic acid. On the other hand, myristoleic acid treatment had little or no influence on early osteoclast differentiation markers, such as c-Fos and NFATc1, and proteins related to cytoskeletal rearrangement, including DC-STAMP, integrin ?v and integrin ?3 in vitro. Taken together, our data suggest that myristoleic acid is capable of blocking the formation of large multinucleated osteoclasts and bone resorption likely through suppressing activation of Src and Pyk2. PMID:26528796

  19. Dentine matrix protein 1 (DMP-1) is a marker of bone formation and mineralisation in soft tissue tumours.

    PubMed

    Inagaki, Y; Kashima, T G; Hookway, E S; Tanaka, Y; Hassan, A B; Oppermann, U; Athanasou, N A

    2015-04-01

    Dentine matrix protein 1 (DMP-1) is a non-collagenous matrix protein found in dentine and bone. It is highly expressed by osteocytes and has been identified in primary benign and malignant osteogenic bone tumours. Bone formation and matrix mineralisation are seen in a variety of benign and malignant soft tissue tumours and tumour-like lesions, and in this study, we analysed immunohistochemically the DMP-1 expression in a wide range of soft tissue lesions (n?=?254) in order to assess whether DMP-1 expression is useful in the histological diagnosis of soft tissue tumours. Matrix staining of DMP-1 was seen in all cases of myositis ossificans, fibro-osseous tumour of the digits, extraskeletal soft tissue osteosarcoma and in most cases of ossifying fibromyxoid tumour. DMP-1 was also noted in dense collagenous connective tissue of mineralising soft tissue lesions such as tumoural calcinosis, dermatomyositis and calcific tendinitis. DMP-1 was expressed in areas of focal ossification and calcification in synovial sarcoma and other soft tissue tumours. With few exceptions, DMP-1 was not expressed in other benign and malignant soft tissue tumours. Our findings indicate that DMP-1 is a matrix marker of bone formation and mineralisation in soft tissue tumours. DMP-1 expression should be particularly useful in distinguishing extraskeletal osteosarcoma and ossifying fibromyxoid tumour from other sarcomas and in identifying areas of osteoid/bone formation and mineralisation in soft tissue tumours. PMID:25630512

  20. The reaction of the dura to bone morphogenetic protein (BMP) in repair of skull defects.

    PubMed Central

    Takagi, K; Urist, M R

    1982-01-01

    Trephine defects in the adult rat skull 0.8 cm in diameter, which do not spontaneously heal, were filled with a bovine bone morphogenetic protein (BMP) fraction. The defects healed not only by bony ingrowth from the trephine rim, but also by proliferation of pervascular mesenchymal-type cells (pericytes) of the dura mater. Under the influence of BMP, dural pericytes differentiated into chondroid and woven bone. Between three and four weeks postimplantation, sinusoids formed and the woven bone remodelled into lamellar bone. Concurrently, blood-borne bone marrow cells colonized the bone deposits, and the diploe were restored. Demonstrating that it is soluble in interstitial fluid, and diffusible across a nucleopore membrane (which isolated the bony margins of the skull), BMP induced new bone formation in the underlying dura and complete repair of the defect. The response of the dura to the BMP fraction produced more new bone than the response to allogeneic bone matrix. The BMP-induced repair was dose dependent; the quantity of new bone was proportional to the dose of the implanted BMP. Images Fig. 1a. Fig. 1b. Fig. 1c. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 8. Fig. 9. PMID:7092346

  1. JMJD3 promotes chondrocyte proliferation and hypertrophy during endochondral bone formation in mice

    PubMed Central

    Zhang, Feng; Xu, Longyong; Xu, Longxia; Xu, Qing; Li, Dangsheng; Yang, Yingzi; Karsenty, Gerard; Chen, Charlie Degui

    2015-01-01

    JMJD3 (KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. However, the function of JMJD3 in vivo is not well understood. Here we show that JMJD3 is highly expressed in cells of the chondrocyte lineage, especially in prehypertrophic and hypertrophic chondrocytes, during endochondral ossification. Homozygous deletion of Jmjd3 results in severely decreased proliferation and delayed hypertrophy of chondrocytes, and thereby marked retardation of endochondral ossification in mice. Genetically, JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes. Biochemically, JMJD3 associates with and enhances RUNX2 activity by derepression of Runx2 and Ihh transcription through its H3K27me3 demethylase activity. These results demonstrate that JMJD3 is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation. PMID:25587042

  2. Single-Dose Local Simvastatin Injection Improves Implant Fixation via Increased Angiogenesis and Bone Formation in an Ovariectomized Rat Model

    PubMed Central

    Tan, Jie; Yang, Ning; Fu, Xin; Cui, Yueyi; Guo, Qi; Ma, Teng; Yin, Xiaoxue; Leng, Huijie; Song, Chunli

    2015-01-01

    Background Statins have been reported to promote bone formation. However, taken orally, their bioavailability is low to the bones. Implant therapies require a local repair response, topical application of osteoinductive agents, or biomaterials that promote implant fixation. Material/Methods The present study evaluated the effect of a single local injection of simvastatin on screw fixation in an ovariectomized rat model of osteoporosis. Results Dual-energy X-ray absorptiometry, micro-computed tomography, histology, and biomechanical tests revealed that 5 and 10 mg simvastatin significantly improved bone mineral density by 18.2% and 22.4%, respectively (P<0.05); increased bone volume fraction by 51.0% and 57.9%, trabecular thickness by 16.4% and 18.9%, trabeculae number by 112.0% and 107.1%, and percentage of osseointegration by 115.7% and 126.3%; and decreased trabeculae separation by 34.1% and 36.6%, respectively (all P<0.01). Bone mineral apposition rate was significantly increased (P<0.01). Furthermore, implant fixation was significantly increased (P<0.05), and bone morphogenetic protein 2 (BMP2) expression was markedly increased. Local injection of a single dose of simvastatin also promoted angiogenesis. Vessel number, volume, thickness, surface area, and vascular volume per tissue volume were significantly increased (all P<0.01). Vascular endothelial growth factor (VEGF), VEGF receptor-2, von Willebrand factor, and platelet endothelial cell adhesion molecule-1 expression were enhanced. Conclusions A single local injection of simvastatin significantly increased bone formation, promoted osseointegration, and enhanced implant fixation in ovariectomized rats. The underlying mechanism appears to involve enhanced BMP2 expression and angiogenesis in the target bone. PMID:25982481

  3. Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone

    PubMed Central

    Xiong, Jinhu; Piemontese, Marilina; Onal, Melda; Campbell, Josh; Goellner, Joseph J.; Dusevich, Vladimir; Bonewald, Lynda; Manolagas, Stavros C.; O’Brien, Charles A.

    2015-01-01

    The cytokine receptor activator of nuclear factor kappa B ligand (RANKL), encoded by the Tnfsf11 gene, is essential for osteoclastogenesis and previous studies have shown that deletion of the Tnfsf11 gene using a Dmp1-Cre transgene reduces osteoclast formation in cancellous bone by more than 70%. However, the Dmp1-Cre transgene used in those studies leads to recombination in osteocytes, osteoblasts, and lining cells making it unclear whether one or more of these cell types produce the RANKL required for osteoclast formation in cancellous bone. Because osteoblasts, osteocytes, and lining cells have distinct locations and functions, distinguishing which of these cell types are sources of RANKL is essential for understanding the orchestration of bone remodeling. To distinguish between these possibilities, we have now created transgenic mice expressing the Cre recombinase under the control of regulatory elements of the Sost gene, which is expressed in osteocytes but not osteoblasts or lining cells in murine bone. Activity of the Sost-Cre transgene in osteocytes, but not osteoblast or lining cells, was confirmed by crossing Sost-Cre transgenic mice with tdTomato and R26R Cre-reporter mice, which express tdTomato fluorescent protein or LacZ, respectively, only in cells expressing the Cre recombinase or their descendants. Deletion of the Tnfsf11 gene in Sost-Cre mice led to a threefold decrease in osteoclast number in cancellous bone and increased cancellous bone mass, mimicking the skeletal phenotype of mice in which the Tnfsf11 gene was deleted using the Dmp1-Cre transgene. These results demonstrate that osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling cancellous bone. PMID:26393791

  4. Chromatin modifiers and histone modifications in bone formation, regeneration, and therapeutic intervention for bone-related disease.

    PubMed

    Gordon, Jonathan A R; Stein, Janet L; Westendorf, Jennifer J; van Wijnen, Andre J

    2015-12-01

    Post-translational modifications of chromatin such as DNA methylation and different types of histone acetylation, methylation and phosphorylation are well-appreciated epigenetic mechanisms that confer information to progeny cells during lineage commitment. These distinct epigenetic modifications have defined roles in bone, development, tissue regeneration, cell commitment and differentiation, as well as disease etiologies. In this review, we discuss the role of these chromatin modifications and the enzymes regulating these marks (methyltransferases, demethylases, acetyltransferases, and deacetylases) in progenitor cells, osteoblasts and bone-related cells. In addition, the clinical relevance of deregulated histone modifications and enzymes as well as current and potential therapeutic interventions targeting chromatin modifiers are addressed. PMID:25836763

  5. LAMELLAR MAGNETISM ASSOCIATED WITH NANOSCALE EXSOLUTION

    E-print Network

    Dunin-Borkowski, Rafal E.

    LAMELLAR MAGNETISM ASSOCIATED WITH NANOSCALE EXSOLUTION IN THE ILMENITE-HEMATITE SOLID SOLUTION-hematite (FeTiO3-Fe2O3) solid solution is one of the most important magnetic phases in nature. Unusual magnetic, magnetic ordering, and exsolution. This presentation describes how this interaction leads to the phenomenon

  6. Lamellar macular hole after intravitreal ocriplasmin injection.

    PubMed

    Chod, Ross Bronson; Goodrich, Clifford; Saxena, Sandeep; Akduman, Levent

    2015-01-01

    Intravitreal ocriplasmin was recently approved by the Food and Drug Administration to achieve medical vitreolysis in the setting of vitreomacular adhesion (VMA). We report a case of a 76-year-old woman who developed a lamellar macular hole following treatment with intravitreal ocriplasmin injection for VMA. A pathophysiological mechanism to explain this previously unreported complication of ocriplasmin injection is proposed. PMID:25576512

  7. trans-10,cis-12 conjugated linoleic acid promotes bone formation by inhibiting adipogenesis by peroxisome proliferator activated receptor-? dependent mechanisms and by directly enhancing osteoblastogenesis from bone marrow mesenchymal stem cells

    PubMed Central

    Kim, Jonggun; Park, Yooheon; Lee, Seong-Ho; Park, Yeonhwa

    2012-01-01

    Bone undergoes continuous remodeling of osteoblastic bone formation and osteoclastic bone resorption to maintain proper bone mass. It is also reported that bone marrow adiposity has a reciprocal role in osteoblasts due to their same origin from mesenchymal stem cells. In addition, one of the key mediators of adipogenesis, peroxisome-proliferator activated receptor-? (PPAR?), plays a significant role in osteoblastogenesis in bone marrow mesenchymal stem cells. One dietary component that is known to have significant impact on adiposity and bone mass is conjugated linoleic acid (CLA). However, the link between controlling adiposity to improving bone mass by CLA has not been studied intensively. Thus the purpose of this study is to determine the role of CLA on bone marrow adiposity and bone formation using murine mesenchymal stem cells. The results confirmed that the trans-10,cis-12 CLA, but not the cis-9,trans-11 CLA isomer, significantly inhibited adipogenesis and promoted osteoblastogenesis from mesenchymal stem cells. The inhibition of adipogenesis by the trans-10,cis-12 CLA was mediated by PPAR?, however, the trans-10,cis-12 CLA had direct effect on osteoblastogenesis which was independent to PPAR? in this model. The trans-10,cis-12 CLA also had significant effects on osteoclastogenesis inhibitory factor (OCIF), which suggests potential influence of CLA on osteoclastogenesis. Overall the results suggest that the trans-10,cis-12, but not the cis-9,trans-11 CLA isomer, has positive impact on bone health by both PPAR? mediated and independent mechanisms in mesenchymal stem cells. PMID:22832076

  8. Morphometric study of the equine navicular bone: variations with breeds and types of horse and influence of exercise

    PubMed Central

    GABRIEL, ANNICK; JOLLY, SANDRA; DETILLEUX, JOHANN; DESSY-DOIZE, CÉCILE; COLLIN, BERNARD; REGINSTER, JEAN-YVES

    1998-01-01

    Navicular bones from the 4 limbs of 95 horses, classified in 9 categories, were studied. The anatomical bases were established for the morphometry of the navicular bone and its variations according to the category of horse, after corrections were made for front or rear limb, sex, weight, size and age. In ponies, navicular bone measurements were smallest for light ponies and regularly increased with body size, but in horses, navicular bone dimensions were smallest for the athletic halfbred, intermediate for draft horse, thoroughbreds and sedentary halfbreds and largest for heavy halfbreds. The athletic halfbred thus showed reduced bone dimensions when compared with other horse types. Navicular bones from 61 horses were studied histomorphometrically. Light horses and ponies possessed larger amounts of cancellous bone and less cortical bone. Draft horses and heavy ponies showed marked thickening of cortical bone with minimum intracortical porosity, and a decrease in marrow spaces associated with more trabecular bone. Two distinct zones were observed for the flexor surface cortex: an external zone composed mainly of poorly remodelled lamellar bone, disposed in a distoproximal oblique direction, and an internal zone composed mainly of secondary bone, with a lateromedial direction for haversian canals. Flexor cortex external zone tended to be smaller for heavy ponies than for the light ponies. It was the opposite for horses, with the largest amount of external zone registered for draft horses. In athletic horses, we observed an increase in the amount of cortical bone at the expense of cancellous bone which could be the result of reduced resorption and increased formation at the corticoendosteal junction. Cancellous bone was reduced for the athletic horses but the number of trabeculae and their specific surfaces were larger. Increased bone formation and reduced resorption could also account for these differences. PMID:10029187

  9. Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

    PubMed Central

    Dumas, Jerald E.; Prieto, Edna M.; Zienkiewicz, Katarzyna J.; Guda, Teja; Wenke, Joseph C.; Bible, Jesse; Holt, Ginger E.

    2014-01-01

    There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

  10. Hybrid use of combined and sequential delivery of growth factors and ultrasound stimulation in porous multilayer composite scaffolds to promote both vascularization and bone formation in bone tissue engineering.

    PubMed

    Yan, Haoran; Liu, Xia; Zhu, Minghua; Luo, Guilin; Sun, Tao; Peng, Qiang; Zeng, Yi; Chen, Taijun; Wang, Yingying; Liu, Keliang; Feng, Bo; Weng, Jie; Wang, Jianxin

    2016-01-01

    In this study, a multilayer coating technology would be adopted to prepare a porous composite scaffold and the growth factor release and ultrasound techniques were introduced into bone tissue engineering to finally solve the problems of vascularization and bone formation in the scaffold whilst the designed multilayer composite with gradient degradation characteristics in the space was used to match the new bone growth process better. The results of animal experiments showed that the use of low intensity pulsed ultrasound (LIPUS) combined with growth factors demonstrated excellent capabilities and advantages in both vascularization and new bone formation in bone tissue engineering. The degradation of the used scaffold materials could match new bone formation very well. The results also showed that only RGD-promoted cell adhesion was insufficient to satisfy the needs of new bone formation while growth factors and LIPUS stimulation were the key factors in new bone formation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 195-208, 2016. PMID:26282063

  11. Muramyl Dipeptide Enhances Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption through Increased RANKL Expression in Stromal Cells

    PubMed Central

    Ishida, Masahiko; Kimura, Keisuke; Sugisawa, Haruki; Aonuma, Tomo; Takada, Haruhiko; Takano-Yamamoto, Teruko

    2015-01-01

    Lipopolysaccharide (LPS) is bacterial cell wall component capable of inducing osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we investigated the effect of MDP in LPS-induced osteoclast formation and bone resorption. LPS was administered with or without MDP into the supracalvariae of mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate-resistant acid phosphatase (TRAP), the ratio of the bone destruction area, the level of tartrate-resistant acid phosphatase form 5b (TRACP 5b), and C-terminal telopeptides fragments of type I collagen as a marker of bone resorption in mice administrated both LPS and MDP were higher than those in mice administrated LPS or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor activator of NF-?B ligand (RANKL) expression and Toll-like receptor 4 (TLR4) expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced mitogen-activated protein kinase (MAPK) signaling, including ERK, p38, and JNK, in stromal cells. These results suggest that MDP might play an important role in pathological bone resorption in bacterial infection diseases. PMID:26000311

  12. In vitro osteogenic differentiation of human mesenchymal stem cells and in vivo bone formation in composite nanofiber meshes.

    PubMed

    Ko, Eun Kyoung; Jeong, Sung In; Rim, Nae Gyune; Lee, Young Moo; Shin, Heungsoo; Lee, Bu-Kyu

    2008-12-01

    Tissue engineering has become an alternative method to traditional surgical treatments for the repair of bone defects, and an appropriate scaffold supporting bone formation is a key element in this approach. In the present study, nanofibrous organic and inorganic composite scaffolds containing nano-sized demineralized bone powders (DBPs) with biodegradable poly(L-lactide) (PLA) were developed using an electrospinning process for engineering bone. To assess their biocompatibility, in vitro osteogenic differentiation of human mandible-derived mesenchymal stem cells (hMSCs) cultured on PLA or PLA/DBP composite nanofiber scaffolds were examined. The mineralization of hMSCs cultured with osteogenic supplements on the PLA/DBP nanofiber scaffolds was remarkably greater than on the PLA nanofiber scaffold during the first 14 days of culture but reached the same level after 21 days. The in vivo osteoconductive effect of PLA/DBP nanofibrous scaffolds was further investigated using rats with critical-sized skull defects. Micro-computerized tomography revealed that a greater amount of newly formed bone extended across the defect area in PLA/DBP scaffolds than in the nonimplant and PLA scaffolds 12 weeks after implantation and that the defect size was almost 90% smaller. Therefore, PLA/DBP composite nanofiber scaffolds may serve as a favorable matrix for the regeneration of bone tissue. PMID:18788980

  13. Processing and mechanical behavior of lamellar structured degradable magnesium-hydroxyapatite implants.

    PubMed

    Ratna Sunil, B; Ganapathy, C; Sampath Kumar, T S; Chakkingal, Uday

    2014-12-01

    Multilayered (laminated) composites exhibit tunable mechanical behavior compared to bulk materials due to the presence of more interfaces and therefore magnesium based composites are gaining wide popularity as biodegradable materials targeted for temporary implant applications. The objective of the present work is to fabricate magnesium based lamellar metal matrix composites (MMCs) for degradable implant applications. Nano-hydroxyapatite (HA) powder was selected as the secondary phase and lamellar structured magnesium-nano-hydroxyapatite (Mg-HA) composites of 8, 10 and 15wt% HA were fabricated by ball milling and spark plasma sintering. It was found that HA particles were coated on the Mg flakes after 20h of ball milling carried out using tungsten carbide (WC) as the milling media. Spark plasma sintering of the milled powders resulted in the formation of lamellar structure of Mg with the presence of HA and magnesium oxide (MgO) at the inter-lamellar sites of the composites. Phase analysis of the milled powder by an X-ray diffraction (XRD) method confirms the presence of HA and MgO along with Mg after sintering. Corrosion behavior of the composites investigated by potentiodynamic polarization tests shows a reduction in the inter-lamellar corrosion with increase in HA content and the best corrosion resistance is found for the Mg-10% HA composite. This composite also exhibits maximum Vickers hardness. Young?s modulus and fracture toughness measured by nano-indentation method were higher for the Mg-8% HA composite. The results thus suggest that lamellar structured Mg composites with 8% and 10% HA show promise for temporary degradable orthopedic implant applications because of their improved corrosion resistance and superior mechanical properties. PMID:25241282

  14. [Frontier in bone biology].

    PubMed

    Takeda, Shu

    2015-10-01

    Bone is an active organ in which bone mass is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption, i.e., coupling of bone formation and bone resorption. Recent advances in molecular bone biology uncovered the molecular mechanism of the coupling. A fundamental role of osteocyte in the maintenance of bone mass and whole body metabolism has also been revealed recently. Moreover, neurons and neuropeptides have been shown to be intimately involved in bone homeostasis though inter-organ network, in addition to "traditional" regulators of bone metabolism such as soluble factors and cytokines PMID:26529922

  15. Effects of lamellar thickness on misfit dislocation introduction and mechanical properties of ?/?2 nano-lamellar TiAl alloys

    NASA Astrophysics Data System (ADS)

    Maruyama, K.; Tabata, A.; Toriyama, Y.; Suzuki, M.; Yoshimi, K.

    2010-07-01

    Stress-strain behavior of lamellar Ti-38Al-3Zr and -3Nb alloys with average lamellar thickness ranging from 10 to 1000 nm were studied at room temperature. Their yield stresses decrease from a high value of coherent lamellar structures to a low value after introducing misfit dislocations onto lamellar boundaries. Their strain hardening rates increase with decreasing lamellar thickness, and then drop to a low level when the misfit dislocations become absent. There is critical thickness of ? lamellae for introduction of misfit dislocations. The thickness decreases with increasing lattice misfit between the constituent phases.

  16. Why Rest Stimulates Bone Formation: A Hypothesis Based on Complex Adaptive Phenomenon

    PubMed Central

    Gross, Ted S.; Poliachik, Sandra L.; Ausk, Brandon J.; Sanford, David A.; Becker, Blair A.; Srinivasan, Sundar

    2006-01-01

    Moderate exercise is an ineffective strategy to build bone mass. The authors present data demonstrating that allowing bone to rest between each load cycle transforms low- and moderate-magnitude mechanical loading into a signal that potently induces bone accretion. They hypothesize that the osteogenic nature of rest-inserted loading arises by enabling osteocytes to communicate as a small world network. PMID:14748543

  17. Autologous serum improves bone formation in a primary stable silica-embedded nanohydroxyapatite bone substitute in combination with mesenchymal stem cells and rhBMP-2 in the sheep model

    PubMed Central

    Boos, Anja M; Weigand, Annika; Deschler, Gloria; Gerber, Thomas; Arkudas, Andreas; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2014-01-01

    New therapeutic strategies are required for critical size bone defects, because the gold standard of transplanting autologous bone from an unharmed area of the body often leads to several severe side effects and disadvantages for the patient. For years, tissue engineering approaches have been seeking a stable, axially vascularized transplantable bone replacement suitable for transplantation into the recipient bed with pre-existing insufficient conditions. For this reason, the arteriovenous loop model was developed and various bone substitutes have been vascularized. However, it has not been possible thus far to engineer a primary stable and axially vascularized transplantable bone substitute. For that purpose, a primary stable silica-embedded nanohydroxyapatite (HA) bone substitute in combination with blood, bone marrow, expanded, or directly retransplanted mesenchymal stem cells, recombinant human bone morphogenetic protein 2 (rhBMP-2), and different carrier materials (fibrin, cell culture medium, autologous serum) was tested subcutaneously for 4 or 12 weeks in the sheep model. Autologous serum lead to an early matrix change during degradation of the bone substitute and formation of new bone tissue. The best results were achieved in the group combining mesenchymal stem cells expanded with 60 ?g/mL rhBMP-2 in autologous serum. Better ingrowth of fibrovascular tissue could be detected in the autologous serum group compared with the control (fibrin). Osteoclastic activity indicating an active bone remodeling process was observed after 4 weeks, particularly in the group with autologous serum and after 12 weeks in every experimental group. This study clearly demonstrates the positive effects of autologous serum in combination with mesenchymal stem cells and rhBMP-2 on bone formation in a primary stable silica-embedded nano-HA bone grafting material in the sheep model. In further experiments, the results will be transferred to the sheep arteriovenous loop model in order to engineer an axially vascularized primary stable bone replacement in clinically relevant size for free transplantation. PMID:25429218

  18. Use of postoperative irradiation for the prevention of heterotopic bone formation after total hip replacement

    SciTech Connect

    Sylvester, J.E.; Greenberg, P.; Selch, M.T.; Thomas, B.J.; Amstutz, H.

    1988-03-01

    Formation of heterotopic bone (HTB) following total hip replacement may partially or completely ankylose the joint space, causing pain and/or limiting the range of motion. Patients at high risk for formation of HTB postoperatively include those with previous HTB formation, heterotopic osteoarthritis, and active rheumatoid spondylitis. Patients in these high risk groups have a 63-69% incidence of post-operative HTB formation, usually seen radiographically by 2 months post-operation. From 1980-1986 twenty-nine hips in 28 consecutively treated patients were irradiated post-operatively at the UCLA Center for the Health Sciences. The indication for irradiation was documented HTB formation previously in 26 of the 27 hips presented below. From 1980-1982 patients received 20 Gray (Gy) in 2 Gy fractions; from 1982-1986 the dose was reduced to 10 Gy in 2 Gy fractions. Twenty-seven hips in 26 patients completed therapy and were available for evaluation, with a minimum of 2 month follow-up, and a median follow-up of 12 months. Three of 27 hips developed significant HTB (Brooker grade III or IV) post-operatively, whereas 5 of 27 hips developed minor, nonsymptomatic HTB (Brooker grade I). When irradiation was begun by postoperative day 4, 0 of 17 hips formed significant HTB. If irradiation began after post-operative day 4, 3 of 10 hips formed significant HTB (Brooker grade III or IV). These 3 hips received doses of 10 Gy in one hip and 20 Gy in the other 2 hips. There were no differences in the incidence or severity of side effects in the 10 Gy vs. the 20 Gy treatment groups. Eighteen hips received 10 Gy, 8 hips 20 Gy and, 1 hip 12 Gy. In conclusion, 10 Gy in 5 fractions appears as effective as 20 Gy in 10 fractions at preventing post-operative formation of HTB. For optimal results, treatment should begin as early as possible prior to post-operative day 4.

  19. The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    PubMed Central

    Ripamonti, U; Richter, P W; Nilen, R W N; Renton, L

    2008-01-01

    Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p-tricalcium phosphate (HA/?-TCP) biomimetic matrices. HA/?-TCP biomimetic matrices in a pre-sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post-sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-?(TGF-?) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/?-TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self-assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF-? superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response. PMID:18363843

  20. Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds

    NASA Technical Reports Server (NTRS)

    Ishaug, S. L.; Crane, G. M.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    Bone formation was investigated in vitro by culturing stromal osteoblasts in three-dimensional (3-D), biodegradable poly(DL-lactic-co-glycolic acid) foams. Three polymer foam pore sizes, ranging from 150-300, 300-500, and 500-710 microns, and two different cell seeding densities, 6.83 x 10(5) cells/cm2 and 22.1 x 10(5) cells/cm2, were examined over a 56-day culture period. The polymer foams supported the proliferation of seeded osteoblasts as well as their differentiated function, as demonstrated by high alkaline phosphatase activity and deposition of a mineralized matrix by the cells. Cell number, alkaline phosphatase activity, and mineral deposition increased significantly over time for all the polymer foams. Osteoblast foam constructs created by seeding 6.83 x 10(5) cells/cm2 on foams with 300-500 microns pores resulted in a cell density of 4.63 x 10(5) cells/cm2 after 1 day in culture; they had alkaline phosphatase activities of 4.28 x 10(-7) and 2.91 x 10(-6) mumol/cell/min on Days 7 and 28, respectively; and they had a cell density that increased to 18.7 x 10(5) cells/cm2 by Day 56. For the same constructs, the mineralized matrix reached a maximum penetration depth of 240 microns from the top surface of the foam and a value of 0.083 mm for mineralized tissue volume per unit of cross sectional area. Seeding density was an important parameter for the constructs, but pore size over the range tested did not affect cell proliferation or function. This study suggests the feasibility of using poly(alpha-hydroxy ester) foams as scaffolding materials for the transplantation of autogenous osteoblasts to regenerate bone tissue.

  1. Collagen immobilization of multi-layered BCP-ZrO2 bone substitutes to enhance bone formation

    NASA Astrophysics Data System (ADS)

    Linh, Nguyen Thuy Ba; Jang, Dong-Woo; Lee, Byong-Taek

    2015-08-01

    A porous microstructure of multi-layered BCP-ZrO2 bone substitutes was fabricated using the sponge replica method in which the highly interconnected structure was immobilized with collagen via ethyl(dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide crosslinking. Their struts are combined with a three-layered BCP/BCP-ZrO2/ZrO2 microstructure. Collagen fibers were firmly attached to the strut surface of the BCP-ZrO2 scaffolds. With control of the three-layered microstructure and collagen immobilization, the compressive strength of the scaffolds increased significantly to 6.8 MPa compared to that of the monolithic BCP scaffolds (1.3 MPa). An in vitro study using MTT, confocal observation, and real-time polymer chain reaction analysis demonstrated that the proliferation and differentiation of the pre-osteoblast-like MC3T3-E1 cells was improved due to the collagen incorporation. Remarkable enhancement of bone regeneration was observed without any immunological reaction in the femurs of rabbits during 1 and 5 months of implantation. Furthermore, the interfaces between new bone and the scaffold struts bonded directly without any gaps.

  2. Freezing and melting water in lamellar structures.

    PubMed

    Gleeson, J T; Erramilli, S; Gruner, S M

    1994-08-01

    The manner in which ice forms in lamellar suspensions of dielaidoylphosphatidylethanolamine, dielaidoylphosphatidylcholine, and dioleoylphosphatidylcholine in water depends strongly on the water fraction. For weight fractions between 15 and 9%, the freezing and melting temperatures are significantly depressed below 0 degree C. The ice exhibits a continuous melting transition spanning as much as 20 degrees C. When the water weight fraction is below 9%, ice never forms at temperatures as low as -40 degrees C. We show that when water contained in a lamellar lipid suspension freezes, the ice is not found between the bilayers; it exists as pools of crystalline ice in equilibrium with the bound water associated with the polar lipid headgroups. We have used this effect, together with the known chemical potential of ice, to measure hydration forces between lipid bilayers. We find exponentially decaying hydration repulsion when the bilayers are less than about 7 A apart. For larger separations, we find significant deviations from single exponential decay. PMID:7948683

  3. Optimal lamellar arrangement in fish gills

    PubMed Central

    Park, Keunhwan; Kim, Wonjung; Kim, Ho-Young

    2014-01-01

    Fish respire through gills, which have evolved to extract aqueous oxygen. Fish gills consist of filaments with well-ordered lamellar structures, which play a role in maximizing oxygen diffusion. It is interesting that when we anatomically observe the gills of various fish species, gill interlamellar distances (d) vary little among them, despite large variations in body mass (Mb). Noting that the small channels formed by densely packed lamellae cause significant viscous resistance to water flow, we construct and test a model of oxygen transfer rate as a function of the lamellar dimensions and pumping pressure, which allows us to predict the optimal interlamellar distance that maximizes the oxygen transfer rate in the gill. Comparing our theory with biological data supports the hypothesis that fish gills have evolved to form the optimal interlamellar distances for maximizing oxygen transfer. This explains the weak scaling dependence of d on Mb: d ? Mb1/6. PMID:24847065

  4. Development of intraosseous infusion of the distal phalanx to access the foot lamellar circulation in the standing, conscious horse.

    PubMed

    Nourian, Ali R; Mills, Paul C; Pollitt, Christopher C

    2010-03-01

    Intraosseous (i.o.) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 microL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood samples were collected at regular intervals and analysed for gentamicin concentrations. Gentamicin was present in lamellar tissue at much higher concentrations than peripheral serum. The mean concentration of gentamicin was 24.4, 20.5 and 4.4 microg/mL in extracellular fluid (ECF) and 0.28, 0.5 and 0.32 microg/mL in serum samples collected 60, 120 and 150 min after IOIDP was started, respectively. A clinically safe and efficacious i.o. drug delivery to the hoof lamellar tissue of standing, conscious horse was developed. PMID:19540781

  5. Changing techniques and indications for lamellar keratoplasty.

    PubMed

    Facskó, A; Nagy, A; Balázs, K; Berta, A

    1997-01-01

    In recent decades, the number of lamellar keratoplasties (LKs) being performed worldwide has been gradually decreasing. However, new technical procedures have been developed and microsurgeons must consider modified indications for lamellar grafting. In the period 1946-1995, in the Department of Ophthalmology University Medical School of Debrecen, Hungary 3889 consecutive keratoplasties were performed of which 608 were LKs. In the period 1946-1960 special surgical material (biosutures) was used without operating microscopes and the leading indication for LK was corneal scar (leukomas). Between 1961 and 1979 with the development of microsurgical procedures (10/0 nylon sutures, operating microscope), the LK technique became more advanced. In the period 1979-1995 precision lamellar grafting could be performed with the widely available improved modern techniques. Changing indications for LK were noted in the second period and this tendency has subsequently continued. Currently the main indications for LK are "immediate" keratoplasty after chemical burns, and sclerokeratoplasty against recurrent pterygia. Their observations lead the authors to conclude that the possible reasons for the changing indications of LK are the new technical procedures, the increasing knowledge, the better immunological tests and the improved postoperative therapy. PMID:9408295

  6. Effects of strontium ranelate on bone formation in the mid-palatal suture after rapid maxillary expansion

    PubMed Central

    Zhao, Shuya; Wang, Xuxia; Li, Na; Chen, Yun; Su, Yuran; Zhang, Jun

    2015-01-01

    Background The aim of this experimental study was to investigate the effects of strontium ranelate on bone regeneration in the mid-palatal suture in response to rapid maxillary expansion (RME). Methods Thirty-six male 6-week-old Wistar rats were randomly divided into three groups, ie, an expansion only (EO) group, an expansion plus strontium ranelate (SE) group, and a control group. An orthodontic appliance was set between the right and left upper molars of rats with an initial expansive force of 0.98 N. Rats in the SE group were administered strontium ranelate (600 mg/kg body weight) and then euthanized in batches on days 4, 7, and 10. Morphological changes in the mid-palatal suture were investigated using micro-computed tomography and hematoxylin and eosin staining after RME. Bone morphogenetic protein-2 expression in the suture was also examined to evaluate bone formation in the mid-palatal suture. Image-Pro Plus software was then used to determine the mean optical density of the immunohistochemical images. Analysis of variance was used for statistical evaluation at the P<0.05 level. Results With expansive force, the mid-palatal suture was expanded, but there was no statistically significant difference (P>0.05) between the SE and EO groups. The bone volume of the suture decreased after RME, but was higher in the SE group than in the EO group on days 7 and 10. Further, expression of bone morphogenetic protein-2 in the SE group was higher than in the other two groups (P<0.05). Conclusion Strontium ranelate may hasten new bone formation in the expanded mid-palatal suture, which may be therapeutically beneficial in prevention of relapse and shortening the retention period after RME. PMID:26056433

  7. Combining bone morphogenetic proteins-2 and -6 has additive effects on osteoblastic differentiation in vitro and accelerates bone formation in vivo.

    PubMed

    Visser, Rick; Bodnarova, Kristina; Arrabal, Pilar M; Cifuentes, Manuel; Becerra, Jose

    2016-01-01

    While only two members of the bone morphogenetic protein subfamily (BMP-2 and -7) are approved to be used in combination with collagen type I in orthopaedic surgery, other BMPs are known to also be highly osteoinductive. Although all the osteogenic BMPs signal through Smad-1/-5/-8 phosphorylation, they show different preferences for the available BMP receptors. In this work we studied the effect of combining two osteogenic BMPs (-2 and -6), which belong to different groups within the subfamily and have different affinities to the existing BMP receptors. Both the growth and in vitro differentiation of MC3T3-E1 mouse preosteoblasts and rat bone marrow-derived mesenchymal stem cells (MSCs) were studied, as well as in vivo ectopic bone formation when the BMPs were intramuscularly implanted in rats with collagen type I sponges as carriers. The results show that these two growth factors have additive effects on the osteoblastic differentiation of cells in vitro and that their combination might be helpful to accelerate in vivo osteogenesis while reducing the amount of each individual BMP used. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 178-185, 2016. PMID:26238281

  8. The real response of bone to exercise

    PubMed Central

    Boyde, Alan

    2003-01-01

    This review presents findings made in studies of large mammalian bones, especially from racehorse training experiments (2–8 years old, third metacarpal, tarsal) and human autopsy orthopaedic femoral implant retrievals and other human biopsy and autopsy cases. Samples were cleaned to analyse mineralized matrix in three dimensions, or poly methyl-methacrylate embedded and micromilled to delete topography and study the superficial c. 0.5-µm two-dimensional section using quantitative backscattered electron imaging. With experimental implant studies in rabbits, observations were also made in vivo using confocal microscopy. Cracks in both calcified cartilage and bone may be removed by infilling with calcified matrix. This may be a general repair mechanism for calcified connective tissue crack repair. The fraction of the organ volume occupied by any form of bone tissue in equine distal third metacarpal extremities was increased in the more exercised groups by bone deposited within former marrow adipocytic space. Where deposited upon prior lamellar bone surfaces, this occurred without the intervention of prior resorption and without the formation of a hypermineralized cement line. Exercise inhibited osteoclastic resorption at external anatomical growth modelling sites where it normally occurs. Addition is not coupled to time-wasting resorption: both internally and externally, it occurs both by layering on existing cancellous surfaces and by creation of new immature scaffold, with de novo incorporation of a rich, capillary blood vessel supply. The real response within bone organs subjected to mechanical overload exercise within normal physiological limits is to make more, and to lose less, bone. PMID:12924818

  9. The real response of bone to exercise.

    PubMed

    Boyde, Alan

    2003-08-01

    This review presents findings made in studies of large mammalian bones, especially from racehorse training experiments (2-8 years old, third metacarpal, tarsal) and human autopsy orthopaedic femoral implant retrievals and other human biopsy and autopsy cases. Samples were cleaned to analyse mineralized matrix in three dimensions, or poly methyl-methacrylate embedded and micromilled to delete topography and study the superficial c. 0.5-microm two-dimensional section using quantitative backscattered electron imaging. With experimental implant studies in rabbits, observations were also made in vivo using confocal microscopy. Cracks in both calcified cartilage and bone may be removed by infilling with calcified matrix. This may be a general repair mechanism for calcified connective tissue crack repair. The fraction of the organ volume occupied by any form of bone tissue in equine distal third metacarpal extremities was increased in the more exercised groups by bone deposited within former marrow adipocytic space. Where deposited upon prior lamellar bone surfaces, this occurred without the intervention of prior resorption and without the formation of a hypermineralized cement line. Exercise inhibited osteoclastic resorption at external anatomical growth modelling sites where it normally occurs. Addition is not coupled to time-wasting resorption: both internally and externally, it occurs both by layering on existing cancellous surfaces and by creation of new immature scaffold, with de novo incorporation of a rich, capillary blood vessel supply. The real response within bone organs subjected to mechanical overload exercise within normal physiological limits is to make more, and to lose less, bone. PMID:12924818

  10. Incorporation of raloxifene-impregnated allograft around orthopedic titanium implants impairs early fixation but improves new bone formation

    PubMed Central

    Hermansen, Lars L; Sørensen, Mette; Barckman, Jeppe; Bechtold, Joan E; Søballe, Kjeld; Baas, Jørgen

    2015-01-01

    Background The anti-osteoporotic drug raloxifene reduces the risk of vertebral fractures by increasing bone mass density. We investigated whether raloxifene offers any benefits in augmenting early fixation of orthopedic implants in the setting of impaction bone grafting. Methods 24 non-weight-bearing grafted gap implants were inserted bilaterally into the tibia of 12 dogs. The 2.5-mm peri-implant gap was filled with either raloxifene-impregnated or untreated bone allograft. Implants were harvested after 28 days. Implant fixation was assessed by mechanical testing and histomorphometric evaluation. Results Raloxifene-treated allograft reduced early implant fixation compared to untreated allograft, as measured by inferior maximum shear strength (p < 0.001) and apparent shear stiffness (p = 0.001). We found that the raloxifene group had more newly formed bone in the gap around the implant (p = 0.02), but also less allograft (p = 0.03). Interpretation The accelerated allograft resorption in the raloxifene group explained the impaired early fixation, despite its stimulation of new bone formation. Our results with local and possible high-dose treatment are not consistent with current theory regarding the mechanism of how systemic raloxifene administration counteracts the decrease in BMD in postmenopausal women. Instead of being solely anti-resorptive as generally held, our results indicate a possible anabolic side of raloxifene. PMID:25175661

  11. Total extract of Korean red ginseng facilitates human bone marrow hematopoietic colony formation in vitro

    PubMed Central

    Kim, Sang-Gyung; Bae, Sung Hwa; Kim, Seong-Mo; Lee, Ji-Hye; Kim, Min Ji; Jang, Hae-Bong

    2014-01-01

    Background The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. Methods Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 µg/mL, 100 µg/mL) or Ginsenoside Rg1 (100 µg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. Results The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6×107 and 1.3-48×107 and 8.9×104 and 1.8-80×104, respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. Conclusion Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage. PMID:25325037

  12. Total Body Irradiation Is Permissive for Mesenchymal Stem Cell-Mediated New Bone Formation Following Local Transplantation

    PubMed Central

    Herberg, Samuel; Kondrikova, Galina; Hussein, Khaled A.; Periyasamy-Thandavan, Sudharsan; Johnson, Maribeth H.; Elsalanty, Mohammed E.; Shi, Xingming; Hamrick, Mark W.; Isales, Carlos M.

    2014-01-01

    Skeletal injury is a major clinical challenge accentuated by the decrease of bone marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease. Numerous experimental and clinical studies have revealed that BMSCs hold great promise for regenerative therapies due to their direct osteogenic potential and indirect trophic/paracrine actions. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in modulating the host response to the injury. Common problems with BMSC therapy include poor cell engraftment, which can be addressed by total body irradiation (TBI) prior to transplantation. In this study, we tested the hypothesis that direct tibial transplantation of BMSCs drives endogenous bone formation in a dose-dependent manner, which is enhanced by TBI, and investigated the potential role of SDF-1 in facilitating these events. We found that TBI is permissive for transplanted BMSCs to engraft and contribute to new bone formation. Bone marrow (BM) interstitial fluid analysis revealed no differences of SDF-1 splice variants in irradiated animals compared to controls, despite the increased mRNA and protein levels expressed in whole BM cells. This correlated with increased dipeptidyl peptidase IV activity and the failure to induce chemotaxis of BMSCs in vitro. We found increased mRNA expression levels of the major SDF-1-cleaving proteases in whole BM cells from irradiated animals suggesting distinct spatial differences within the BM in which SDF-1 may play different autocrine and paracrine signaling roles beyond the immediate cell surface microenvironment. PMID:24914464

  13. Total body irradiation is permissive for mesenchymal stem cell-mediated new bone formation following local transplantation.

    PubMed

    Herberg, Samuel; Kondrikova, Galina; Hussein, Khaled A; Periyasamy-Thandavan, Sudharsan; Johnson, Maribeth H; Elsalanty, Mohammed E; Shi, Xingming; Hamrick, Mark W; Isales, Carlos M; Hill, William D

    2014-12-01

    Skeletal injury is a major clinical challenge accentuated by the decrease of bone marrow-derived mesenchymal stem/stromal cells (BMSCs) with age or disease. Numerous experimental and clinical studies have revealed that BMSCs hold great promise for regenerative therapies due to their direct osteogenic potential and indirect trophic/paracrine actions. Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1) is involved in modulating the host response to the injury. Common problems with BMSC therapy include poor cell engraftment, which can be addressed by total body irradiation (TBI) prior to transplantation. In this study, we tested the hypothesis that direct tibial transplantation of BMSCs drives endogenous bone formation in a dose-dependent manner, which is enhanced by TBI, and investigated the potential role of SDF-1 in facilitating these events. We found that TBI is permissive for transplanted BMSCs to engraft and contribute to new bone formation. Bone marrow (BM) interstitial fluid analysis revealed no differences of SDF-1 splice variants in irradiated animals compared to controls, despite the increased mRNA and protein levels expressed in whole BM cells. This correlated with increased dipeptidyl peptidase IV activity and the failure to induce chemotaxis of BMSCs in vitro. We found increased mRNA expression levels of the major SDF-1-cleaving proteases in whole BM cells from irradiated animals suggesting distinct spatial differences within the BM in which SDF-1 may play different autocrine and paracrine signaling roles beyond the immediate cell surface microenvironment. PMID:24914464

  14. ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

    PubMed Central

    2012-01-01

    Introduction Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases. Methods To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic breast tumors. Results ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo. Finally, conditioned media from breast cancer cells with reduced ABCC5 expression failed to induce in vitro osteoclastogenesis to the same extent as conditioned media from breast cancer cells expressing ABCC5. Conclusions Our data suggest that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for efficient osteoclast-mediated bone resorption. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis. PMID:23174366

  15. Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery

    NASA Technical Reports Server (NTRS)

    Ishaug-Riley, S. L.; Crane, G. M.; Gurlek, A.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

  16. Bare Bones Pattern Formation: A Core Regulatory Network in Varying Geometries Reproduces Major

    E-print Network

    Zhang, Yong-Tao

    propensity to form limb-like skeletal structures. The bare bones framework can accommodate ancillary gene parameter values, those of experimentally manipulated, genetically aberrant and evolutionary early forms

  17. A histomorphometric study of the effect of doxycycline and erythromycin on bone formation in dental alveolar socket of rat

    PubMed Central

    Shahabooei, Mohammad; Razavi, Sayed Mohammad; Minaiyan, Mohsen; Birang, Reza; Behfarnia, Parichehr; Yaghini, Jaber; Naghsh, Narges; Ghalayani, Parichehr; Hajisadeghi, Samira

    2015-01-01

    Background: The aim of the present study was to evaluate whether subantimicrobial doses of doxycycline (DOX) and erythromycin (EM) used for the treatment of peri-implant osteolysis due to their anti-osteoclastogenesis can interfere with the osseous wound healing process in rat alveolar socket. Materials and Methods: Forty-five male Wistar rats had their first maxillary right molar extracted and were divided into three groups. DOX and EM at the doses of 5 mg/kg/day orally (p.o.) and 2 mg/kg/day intraperitoneally (i.p.) were administered respectively to two separate groups for 7 days after operation. In the control group the animals received normal saline (5 ml/kg). Five rats were sacrificed at 7, 14 and 21 days post-extraction in each study group. A histomorphometric analysis was used to evaluate new bone formation inside the alveolar socket. Significant level was set at 0.05. Results: The findings showed that the percentage of new bone formation (NBF) enhanced significantly on days 7 and 14. There was no significant difference in the NBF between DOX and EM groups. Conclusion: Short-term treatment with both DOX and EM enhanced new bone formation without any advances in favor of each drug. PMID:25878996

  18. P38 MAPK / beta-catenin canonical wnt signaling mediated bone formation effects of blueberries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Appropriate nutrition is one of the critical factors that influences bone development. We studied the effects of dietary blueberry supplementation on bone growth in weanling rats. Weanling male and female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder for 14 a...

  19. Culture medium of bone marrow-derived human mesenchymal stem cells effects lymphatic endothelial cells and tumor lymph vessel formation

    PubMed Central

    ZHAN, JIE; LI, YAHONG; YU, JING; ZHAO, YUANYAUN; CAO, WENMING; MA, JIE; SUN, XIAOXIAN; SUN, LI; QIAN, HUI; ZHU, WEI; XU, WENRONG

    2015-01-01

    Human bone marrow mesenchymal stem cells (hBM-MSCs) favor tumor growth and metastasis in vivo and in vitro. Neovascularization is involved in several pathological conditions, including tumor growth and metastasis. Previous studies have demonstrated that human bone marrow MSC-derived conditioned medium (hBM-MSC-CM) can promote tumor growth by inducing the expression of vascular epidermal growth factor (VEGF) in tumor cells. However, the effect of BM-MSCs on tumor lymph vessel formation has yet to be elucidated. In the present study, the effect of BM-MSCs on processes involved in lymph vessel formation, including tube formation, migration and proliferation, was investigated in human-derived lymphatic endothelial cells (HDLECs). It was identified that hBM-MSC-CM promoted the tube formation and migration of HDLECs. In addition, tumor cells were revealed to participate in lymph vessel formation. In the present study, the SGC-7901, HGC-27 and GFP-MCF-7 cell lines were treated with hBM-MSC-CM. The results demonstrated that the expression of the lymph-associated markers, prospero homeobox protein 1 and VEGF receptor-3, were increased in the SGC-7901 and HGC-27 cell lines, but not in the GFP-MCF-7 cells. The tube formation assay demonstrated that the HGC-27 cells treated with hBM-MSC-CM for 20 days underwent tube formation. These findings indicate that hBM-MSC-CM can promote tube formation in HDLECs and HGC-27 cells, which may be associated with lymph vessel formation during tumor growth and metastasis. PMID:25663886

  20. Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold

    PubMed Central

    Lv, Y. M.; Yu, Q. S.

    2015-01-01

    Objectives The major problem with repair of an articular cartilage injury is the extensive difference in the structure and function of regenerated, compared with normal cartilage. Our work investigates the feasibility of repairing articular osteochondral defects in the canine knee joint using a composite lamellar scaffold of nano-ß-tricalcium phosphate (ß-TCP)/collagen (col) I and II with bone marrow stromal stem cells (BMSCs) and assesses its biological compatibility. Methods The bone–cartilage scaffold was prepared as a laminated composite, using hydroxyapatite nanoparticles (nano-HAP)/collagen I/copolymer of polylactic acid–hydroxyacetic acid as the bony scaffold, and sodium hyaluronate/poly(lactic-co-glycolic acid) as the cartilaginous scaffold. Ten-to 12-month-old hybrid canines were randomly divided into an experimental group and a control group. BMSCs were obtained from the iliac crest of each animal, and only those of the third generation were used in experiments. An articular osteochondral defect was created in the right knee of dogs in both groups. Those in the experimental group were treated by implanting the composites consisting of the lamellar scaffold of ß-TCP/col I/col II/BMSCs. Those in the control group were left untreated. Results After 12 weeks of implantation, defects in the experimental group were filled with white semi-translucent tissue, protruding slightly over the peripheral cartilage surface. After 24 weeks, the defect space in the experimental group was filled with new cartilage tissues, finely integrated into surrounding normal cartilage. The lamellar scaffold of ß-TCP/col I/col II was gradually degraded and absorbed, while new cartilage tissue formed. In the control group, the defects were not repaired. Conclusion This method can be used as a suitable scaffold material for the tissue-engineered repair of articular cartilage defects. Cite this article: Bone Joint Res 2015;4:56–64 PMID:25837672

  1. Bone formation around rhBMP-2-coated implants in rabbit sinuses with or without absorbable collagen sponge grafting

    PubMed Central

    2015-01-01

    Purpose The purpose of this study was to evaluate bone formation around recombinant human bone morphogenetic protein (rhBMP-2)-coated implants placed with or without absorbable collagen sponge (ACS) in rabbit maxillary sinuses. Methods The Schneiderian membrane was elevated and an implant was placed in 24 sinuses in 12 rabbits. The space created beneath the elevated membrane was filled with either blood (n=6) or ACS (n=6). In the rabbits in which this space was filled with blood, rhBMP-2-coated and non-coated implants were alternately placed on different sides. The resulting groups were referred to as the BC and BN groups, respectively. The AC and AN groups were produced in ACS-grafted rabbits in the same manner. Radiographic and histomorphometric analyses were performed after eight weeks of healing. Results In micro-computed tomography analysis, the total augmented volume and new bone volume were significantly greater in the ACS-grafted sinuses than in the blood-filled sinuses (P<0.05). The histometric analysis showed that the areas of new bone and bone-to-implant contact were significantly larger in the AC group than in the AN group (P<0.05). In contrast, none of the parameters differed significantly between the BC and BN groups. Conclusions The results of this pilot study indicate that the insertion of ACS after elevating the Schneiderian membrane, simultaneously with implant placement, can significantly increase the volume of the augmentation. However, in the present study, the rhBMP-2 coating exhibited limited effectiveness in enhancing the quantity and quality of regenerated bone.

  2. Study of in Vitro and in Vivo Bone Formation in Composite Cryogels and the Influence of Electrical Stimulation

    PubMed Central

    Mishra, Ruchi; Raina, Deepak Bushan; Pelkonen, Mea; Lidgren, Lars; Tägil, Magnus; Kumar, Ashok

    2015-01-01

    This work studies osteoinduction and bone conduction in polyvinyl alcohol-tetraethylorthosilicate-alginate-calcium oxide (PTAC) biocomposite cryogels along with the synergistic effect of electrical stimulation. In vitro osteoinduction of C2C12 myoblast towards osteogenic lineage is demonstrated through alkaline phosphatase assay, scanning electron microscopy and energy dispersive X-ray spectroscopy. These results were followed by in vivo implantation studies of PTAC biocomposite cryogel scaffolds in the bone conduction chamber model depicting bone formation after 24 days based on immunohistological staining for osteogenic markers, i.e., collagen type I (Col I), osteocalcin (OCN), osteopontin (OPN) and bone sialoprotein (BSP). Further, osteogenic differentiation of murine mesenchymal stem cells was studied with and without electrical stimulation. The q-PCR analysis shows that the electrically stimulated cryogels exhibit ~ 6 folds higher collagen type I and ~ 10 folds higher osteopontin mRNA level, in comparison to the unstimulated cryogels. Thus, PTAC biocomposite cryogels present osteoinductive and osteoconductive properties during in vitro and in vivo studies and support osteogenic differentiation of mesenchymal stem cells under the influence of electrical stimulation. PMID:26535027

  3. Commercial Honeybush (Cyclopia spp.) Tea Extract Inhibits Osteoclast Formation and Bone Resorption in RAW264.7 Murine Macrophages—An in vitro Study

    PubMed Central

    Visagie, Amcois; Kasonga, Abe; Deepak, Vishwa; Moosa, Shaakirah; Marais, Sumari; Kruger, Marlena C.; Coetzee, Magdalena

    2015-01-01

    Honeybush tea, a sweet tasting caffeine-free tea that is indigenous to South Africa, is rich in bioactive compounds that may have beneficial health effects. Bone remodeling is a physiological process that involves the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. When resorption exceeds formation, bone remodeling can be disrupted resulting in bone diseases such as osteoporosis. Osteoclasts are multinucleated cells derived from hematopoietic precursors of monocytic lineage. These precursors fuse and differentiate into mature osteoclasts in the presence of receptor activator of NF-kB ligand (RANKL), produced by osteoblasts. In this study, the in vitro effects of an aqueous extract of fermented honeybush tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macrophages. We found that commercial honeybush tea extract inhibited osteoclast formation and TRAP activity which was accompanied by reduced bone resorption and disruption of characteristic cytoskeletal elements of mature osteoclasts without cytotoxicity. Furthermore, honeybush tea extract decreased expression of key osteoclast specific genes, matrix metalloproteinase-9 (MMP-9), tartrate resistant acid phosphatase (TRAP) and cathepsin K. This study demonstrates for the first time that honeybush tea may have potential anti-osteoclastogenic effects and therefore should be further explored for its beneficial effects on bone. PMID:26516894

  4. Inhibition of dioxin effects on bone formation in vitro by a newly described aryl hydrocarbon receptor antagonist, resveratrol.

    PubMed

    Singh, S U; Casper, R F; Fritz, P C; Sukhu, B; Ganss, B; Girard, B; Savouret, J F; Tenenbaum, H C

    2000-10-01

    Aryl hydrocarbon receptor (AhR) ligands are environmental contaminants found in cigarette smoke and other sources of air pollution. The prototypical compound is TCDD (2,3,7, 8-tetrachlorodibenzo-p-dioxin), also known as dioxin. There is an increasing body of knowledge linking cigarette smoking to osteoporosis and periodontal disease, but the direct effects of smoke-associated aryl hydrocarbons on bone are not well understood. Through the use of resveratrol (3,5,4'-trihydroxystilbene), a plant antifungal compound that we have recently demonstrated to be a pure AhR antagonist, we have investigated the effects of TCDD on osteogenesis. It was postulated that TCDD would inhibit osteogenesis in bone-forming cultures and that this inhibition would be antagonized by resveratrol. We employed the chicken periosteal osteogenesis (CPO) model, which has been shown to form bone in vitro in a pattern morphologically and biochemically similar to that seen in vivo, as well as a rat stromal cell bone nodule formation model. In the CPO model, alkaline phosphatase (AP) activity was reduced by up to 50% (P<0.01 vs control) in the presence of 10(-9) M TCDD and these effects were reversed by 10(-6) M resveratrol (P<0.05 vs TCDD alone). TCDD-mediated inhibition of osteogenesis was restricted primarily to the osteoblastic differentiation phase (days 0-2) as later addition did not appear to have any effects. Message levels for important bone-associated proteins (in the CPO model) such as collagen type I, osteopontin, bone sialoprotein and AP were inhibited by TCDD, an effect that was antagonized by resveratrol. Similar findings were obtained using the rat stromal bone cell line. TCDD (at concentrations as low as 10(-10)M) caused an approximately 33% reduction in AP activity, which was abrogated by 3. 5x10(-7) M resveratrol. TCDD also induced a marked reduction in mineralization ( approximately 75%) which was completely antagonized by resveratrol. These data suggest that AhR ligands inhibit osteogenesis probably through inhibition of osteodifferentiation and that this effect can be antagonized by resveratrol. Since high levels of AhR ligands are found in cigarette smoke, and further since smoking is an important risk factor in both osteoporosis and periodontal disease, it may be postulated that AhR ligands are the component of cigarette smoke linking smoking to osteoporosis and periodontal disease. If so, resveratrol could prove to be a promising preventive or therapeutic agent for smoking-related bone loss. PMID:11018766

  5. Alpha-Lipoic Acid Promotes Osteoblastic Formation in H2O2 -Treated MC3T3-E1 Cells and Prevents Bone Loss in Ovariectomized Rats.

    PubMed

    Fu, Chao; Xu, Dong; Wang, Chang-Yuan; Jin, Yue; Liu, Qi; Meng, Qiang; Liu, Ke-Xin; Sun, Hui-Jun; Liu, Mo-Zhen

    2015-09-01

    Alpha-lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. Recently, accumulating evidences has indicated the relationship between oxidative stress and osteoporosis (OP). Some studies have investigated the possible beneficial effects of ALA on OP both in vivo and in vitro; however, the precise mechanism(s) underlying the bone-protective action of ALA remains unclear. Considering this, we focused on the anti-oxidative capacity of ALA to exert bone-protective effects in vitro and in vivo. In the present study, the effects of ALA on osteoblastic formation in H(2)O(2) -treated MC3T3-E1 pre-osteoblasts and ovariectomy (OVX)-induced bone loss in rats were investigated. The results showed that ALA promoted osteoblast differentiation, mineralization and maturation and inhibited osteoblast apoptosis, thus increasing the OPG/receptor activator of nuclear factor-?B (NF-?B) ligand (RANKL) ratio and leading to enhanced bone formation in vitro and inhibited bone loss in vivo. Further study revealed that ALA exerted its bone-protective effects by inhibiting reactive oxygen species (ROS) generation by down-regulating Nox4 gene expression and protein synthesis and attenuating the transcriptional activation of NF-?B. In addition, ALA might exert its bone-protective effects by activating the Wnt/Lrp5/?-catenin signaling pathway. Taken together, the present study indicated that ALA promoted osteoblastic formation in H(2)O(2) -treated MC3T3-E1 cells and prevented OVX-induced bone loss in rats by regulating Nox4/ROS/NF-?B and Wnt/Lrp5/?-catenin signaling pathways, which provided possible mechanisms of bone-protective effects in regulating osteoblastic formation and preventing bone loss. Taken together, the results suggest that ALA may be a candidate for clinical OP treatment. PMID:25655087

  6. In vitro and in vivo studies of surface-structured implants for bone formation

    PubMed Central

    Xia, Lu; Feng, Bo; Wang, Peizhi; Ding, Siyang; Liu, Zhiyuan; Zhou, Jie; Yu, Rong

    2012-01-01

    Background and methods Micronanoscale topologies play an important role in implant osteointegration and determine the success of an implant. We investigated the effect of three different implant surface topologies on osteoblast response and bone regeneration. In this study, implants with nanotubes and micropores were used, and implants with flat surfaces were used as the control group. Results Our in vitro studies showed that the nanostructured topologies improved the proliferation, differentiation, and development of the osteoblastic phenotype. Histological analysis further revealed that the nanotopology increased cell aggregation at the implant-tissue interfaces and enhanced bone-forming ability. Pushout testing indicated that the nanostructured topology greatly increased the bone-implant interfacial strength within 4 weeks of implantation. Conclusion Nanotopography may improve regeneration of bone tissue and shows promise for dental implant applications. PMID:23028216

  7. Chain confinement, phase transitions, and lamellar structure in semicrystalline polymers, polymer blends and polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Chen, Huipeng

    Recent studies suggest that there are three phase fractions in semicrystalline polymers, the crystalline, the mobile amorphous and the rigid amorphous phases. Due to the distinct properties of the rigid amorphous fraction, RAF, it has been investigated for more than twenty years. In this thesis, a general method using quasi-isothermal temperature-modulated differential scaning calorimetry, DSC, is provided for the first time to obtain the temperature dependent RAF and the other two fractions, crystalline fraction and mobile amorphous fraction, MAF. For poly(ethylene terephthalate), PET, our results show RAF was vitrified during quasi-isothermal cooling after crystallization had been completed and became totally devitrified during quasi-isothermal heating before the start of melting. Several years after people initially discovered the existence of RAF, another issue arose relating to the physical location of RAF and mobile amorphous fraction, MAF, within a lamellar stack model. Two very different models to describe the location of RAF were proposed. In the Heterogeneous Stack Model, HET, RAF is located outside the lamellar stacks. In the Homogeneous Stack Model, HSM, RAF was located inside the lamellar stacks. To determine the lamellar structure of semicrystalline polymers comprising three phase, a general method is given in this thesis by using a combination of the DSC and small angle X-ray scattering, SAXS techniques. It has been applied to Nylon 6, isotactic polystyrene, iPS, and PET. It was found for all of these materials, the HSM model is correct to describe the lamellar structure. In addition to the determination of lamellar structures, this method can also provide the exact fraction of MAF inside and outside lamellar stacks for binary polymer blends. For binary polymer blends, MAF, normally is located partially inside and partially outside the lamellar stacks. However, the quantification of the MAF inside and outside the lamellar stacks has now been provided and is applied to the iPS/atactic polystyrene, aPS, blends. The fractions of MAF inside and outside the lamellar stacks were quantified for the first time. For A/B binary polymer blends, it has been reported that if B is already crystalline, the crystalline fraction would serve as a restriction on the subsequent growth of the crystallizable partner A, while amorphous fraction could be diffused from the crystalline growth front of the crystallizing A component. Considering the effect of RAF on binary blends, a new concept is provided: like the crystals, the RAF of one polymer component may inhibit the growth of crystals of the other blend partner. The non-isothermal crystallization of PET/poly(lactic acid), PLA, blends were investigated and the results confirmed the new concept is correct: PET forms a large amount of RAF and inhibits crystal formation in PLA. Then, we broadened the concept of RAF and investigated the RAF in recent 'hot' materials, polymer nanocomposites. It was found the fraction of RAF greatly increased with a small amount of multi-wall carbon nanotubes, MWCNT, loading in PET electrospun, ES, fibers. A general model is given for polymer ES fibers with MWCNTs: the addition of MWCNTs causes polymer chains in the ES fibers to become more extended, (ie, more stretched), resulting in more confinement of PET chains and an increase in the RAF.

  8. Conditional disruption of miR17-92 cluster in collagen type I-producing osteoblasts results in reduced periosteal bone formation and bone anabolic response to exercise.

    PubMed

    Mohan, Subburaman; Wergedal, Jon E; Das, Subhashri; Kesavan, Chandrasekhar

    2015-02-01

    In this study, we evaluated the role of the microRNA (miR)17-92 cluster in osteoblast lineage cells using a Cre-loxP approach in which Cre expression is driven by the entire regulatory region of the type I collagen ?2 gene. Conditional knockout (cKO) mice showed a 13-34% reduction in total body bone mineral content and area with little or no change in bone mineral density (BMD) by DXA at 2, 4, and 8 wk in both sexes. Micro-CT analyses of the femur revealed an 8% reduction in length and 25-27% reduction in total volume at the diaphyseal and metaphyseal sites. Neither cortical nor trabecular volumetric BMD was different in the cKO mice. Bone strength (maximum load) was reduced by 10% with no change in bone toughness. Quantitative histomorphometric analyses revealed a 28% reduction in the periosteal bone formation rate and in the mineral apposition rate but with no change in the resorbing surface. Expression levels of periostin, Elk3, Runx2 genes that are targeted by miRs from the cluster were decreased by 25-30% in the bones of cKO mice. To determine the contribution of the miR17-92 cluster to the mechanical strain effect on periosteal bone formation, we subjected cKO and control mice to 2 wk of mechanical loading by four-point bending. We found that the periosteal bone response to mechanical strain was significantly reduced in the cKO mice. We conclude that the miR17-92 cluster expressed in type I collagen-producing cells is a key regulator of periosteal bone formation in mice. PMID:25492928

  9. Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Whalen, Robert T.; Fung, Paul; Sherrard, Donald J.; Maloney, Norma

    1992-01-01

    The -6-deg head-down tilt (HDT) is employed in the study of 8 subjects to determine early responses in human bone and calcium endocrines during spaceflight. The average rates of bone formation in the iliac crest are determined by means of a single-dose labeling schedule and are found to decrease in 6 of the subjects. The decrease varies directly with walking miles, and increased excretion of urinary Ca and Na are observed preceding increased levels of ionized serum calcium on a bed-rest day late in the week. Reduced phosphorous excretions are also followed by increased serum phosphorous on day six, and reductions are noted in parathyroid hormone and vitamin D by the end of the experiment. The data demonstrate the responsiveness of the skeletal system to biomechanical stimuli such as the HDT.

  10. The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children

    PubMed Central

    Wawrzyk, Magdalena; Sokal, Jan; Andrzejewska, Ewa; Przewratil, Przemys?aw

    2015-01-01

    Summary Background In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. Material/Methods The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. Results Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the fragments, were 3 times more common in girls. Statistical analysis of the measurements of length and width of the callus demonstrated that the differences between results obtained in the ultrasound in comparison with X-rays were not statistically significant. Moreover, preliminary results showed a significantly higher degree of vascularization of the callus than of the healthy periosteum. Conclusions Preliminary results indicate the high efficacy of ultrasound in the evaluation of callus formation after fractures of long bones in children and the possibility of its alternative use to X-ray examinations. PMID:26543512

  11. Assessment of a new biomimetic scaffold and its effects on bone formation by OCT

    NASA Astrophysics Data System (ADS)

    Yang, Ying; Aydin, Halil M.; Piskin, Erhan; El Haj, Alicia J.

    2009-02-01

    The ultimate target of bone tissue engineering is to generate functional load bearing bone. By nature, the porous volume in the trabecular bone is occupied by osseous medulla. The natural bone matrix consists of hydroxyapatite (HA) crystals precipitated along the collagen type I fibres. The mineral phase renders bone strength while collagen provides flexibility. Without mineral component, bone is very flexible and can not bear loads, whereas it is brittle in the case of mineral phase without the collagen presence. In this study, we designed and prepared a new type of scaffold which mimics the features of natural bone. The scaffold consists of three different components, a biphasic polymeric base composed of two different biodegradable polymers prepared by using dual porogen approach and bioactive agents, i.e., collagen and HA particles which are distributed throughout the matrix only in the pore surfaces. Interaction of the bioactive scaffolds possessing very high porosity and interconnected pore structures with cells were investigated in a prolonged culture period by using an osteoblastic cell line. The mineral HA particles have a slight different refractive index from the other elements such as polymeric scaffolds and cell/matrix in a tissue engineering constructs, exhibiting brighter images in OCT. Thus, OCT renders a convenient means to assess the morphology and architecture of the blank biomimetic scaffolds. This study also takes a close observation of OCT images for the cultured cell-scaffold constructs in order to assess neo-formed minerals and matrix. The OCT assessments have been compared with the results from confocal and SEM analysis.

  12. Load transfer in bovine plexiform bone determined by synchrotron x-ray diffraction.

    SciTech Connect

    Akhtar, R.; Daymond, M.; Almer, J.; Mummery, P.; The Univ. of Manchester; Queen's Univ.

    2008-02-01

    High-energy synchrotron x-ray diffraction (XRD) has been used to quantify load transfer in bovine plexiform bone. By using both wide-angle and small-angle XRD, strains in the mineral as well as the collagen phase of bone were measured as a function of applied compressive stress. We suggest that a greater proportion of the load is borne by the more mineralized woven bone than the lamellar bone as the applied stress increases. With a further increase in stress, load is shed back to the lamellar regions until macroscopic failure occurs. The reported data fit well with reported mechanisms of microdamage accumulation in bovine plexiform bone.

  13. Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis.

    PubMed

    Thudium, C S; Jensen, V K; Karsdal, M A; Henriksen, K

    2012-03-01

    The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and mutations in a3 lead to infantile malignant osteopetrosis, a phenomenon characterized by increased bone mass, an increased number of non-resorbing osteoclasts, and a complete lack of bone resorption. Importantly, these individuals have normal or even increased osteoblast numbers and bone formation suggesting that the osteoclasts, but not their resorptive capability, relay an anabolic signal, and, hence, that bone formation can be uncoupled from bone resorption when the a3 subunit is eliminated by mutations, or possibly by pharmacological intervention. The pharmacological profile of the a3 subunit as a highly specific target with a mode of action profile augmenting uncoupling and sustained bone formation, as derived from osteopetrotic patients and mice, highlights the relevance of the V-ATPase in future osteoporosis drug development. However, as illustrated by numerous attempts at developing specific inhibitors of the osteoclastic V-ATPase it is a very difficult target to work with, and an inhibitor possessing the desired profile remains elusive, although highly promising approaches recently have been launched. PMID:22044152

  14. Ectopic Bone Formation by Mesenchymal Stem Cells Derived from Human Term Placenta and the Decidua

    PubMed Central

    Gronthos, Stan; Manuelpillai, Ursula; Abumaree, Mohamed H.; Pertile, Mark D.; Brennecke, Shaun P.; Kalionis, Bill

    2015-01-01

    Mesenchymal stem cells (MSCs) are one of the most attractive cell types for cell-based bone tissue repair applications. Fetal-derived MSCs and maternal-derived MSCs have been isolated from chorionic villi of human term placenta and the decidua basalis attached to the placenta following delivery, respectively. Chorionic-derived MSCs (CMSCs) and decidua-derived MSCs (DMSCs) generated in this study met the MSCs criteria set by International Society of Cellular Therapy. These criteria include: (i) adherence to plastic; (ii) >90% expression of CD73, CD105, CD90, CD146, CD44 and CD166 combined with <5% expression of CD45, CD19 and HLA-DR; and (iii) ability to differentiate into osteogenic, adipogenic, and chondrogenic lineages. In vivo subcutaneous implantation into SCID mice showed that both bromo-deoxyuridine (BrdU)-labelled CMSCs and DMSCs when implanted together with hydroxyapatite/tricalcium phosphate particles were capable of forming ectopic bone at 8-weeks post-transplantation. Histological assessment showed expression of bone markers, osteopontin (OPN), osteocalcin (OCN), biglycan (BGN), bone sialoprotein (BSP), and also a marker of vasculature, alpha-smooth muscle actin (?-SMA). This study provides evidence to support CMSCs and DMSCs as cellular candidates with potent bone forming capacity. PMID:26484666

  15. Body fat loss induced by calcium in co-supplementation with conjugated linoleic acid is associated with increased expression of bone formation genes in adult mice.

    PubMed

    Chaplin, Alice; Palou, Andreu; Serra, Francisca

    2015-12-01

    The potential of conjugated linoleic acids (CLA) and calcium in weight management in animal models and human studies has been outlined, as well as their use to prevent bone loss at critical stages. In addition, it has been suggested that bone remodeling and energy metabolism are regulated by shared pathways and involve common hormones such as leptin. We have previously shown that supplementation with CLA and calcium in adult obese mice decreases body weight and body fat. The aim of the present study was to assess the effects of these two compounds on bone and energy metabolism markers on bone. Mice (C57BL/6J) were divided into five groups according to diet and treatment (up to 56 days): control (C), high-fat diet (HF), HF+CLA (CLA), HF+calcium (Ca) and HF with both compounds (CLA+Ca). At the end of treatment, bone formation markers were determined in plasma and expression of selected bone and energy markers was determined in tibia by quantitative polymerase chain reaction. Results show that CLA was associated with decreased tibia weight and minor impact on bone markers, whereas calcium, either alone or co-supplemented with CLA, maintained bone weight and promoted the expression of bone formation genes such as bone gamma-carboxyglutamate protein 2 (Bglap2) and collagen I?1 (Col1a1). Furthermore, it had a significant effect on key players in energy metabolism, in particular leptin and adiponectin tibia receptors. Overall, in addition to the weight loss promoting properties of calcium, on its own or co-supplemented with CLA, our results support beneficial effects on bone metabolism in mice. PMID:26454511

  16. Ultrafine fully-lamellar structures in two-phase {gamma}-TiAl alloys

    SciTech Connect

    Maziasz, P.J.; Liu, C.T.

    1996-12-31

    Special ultrafine fully lamellar microstructures have been found recently in {gamma}-TiAl alloys with 46-48% Al processed or heat treated above the {alpha}-transus temperature (T{alpha}). Hot extrusion above T{alpha} also produces a refined colony or grain size. Refined-colony/ultrafine-lamellar (RC/UL) microstructures produce an excellent combination of RT ductility and high-temperature strength in Ti-47Al-2Cr-2Nb (at.%) alloys. UL structures also have regularly alternating {gamma} and {alpha}{sub 2} lamellae, such that they are dominated by {gamma}/{alpha}{sub 2} interfaces with relatively few {gamma}/{gamma} twin boundaries. Focus of this study is on how changes in processing parameters or alloy composition affect formation of the UL structure, particularly the {alpha}{sub 2} component.

  17. Effects of the antiepileptics phenytoin and zonisamide on dentin formation and bone mineral density of the mandible in growing rats.

    PubMed

    Takahashi, A; Saito, T; Mayanagi, H; Kamei, J; Onodera, K

    2004-12-01

    This study was undertaken to examine the effects of the antiepileptics phenytoin and zonisamide on changes in the mineral density of the incisor and bone mineral density (BMD) of the mandibular head, and on the rate of dentin formation using histomorphometric measurements. After repeated administration of phenytoin or zonisamide to male growing rats, the mineral density of the lower incisors and mandibular head were determined by analyzing microradiographs and dentin formation rates were determined by histomorphometric measurements. Results showed a significant decrease in the mean values of BMD of the mandibular head and lower incisors in groups treated with phenytoin or zonisamide compared with the vehicle-treated group (p < 0.05). The percent rates of decrease in mineral density of the incisors for phenytoin and zonisamide were 6.8% and 4.0%, respectively. Phenytoin and zonisamide significantly reduced the dentin formation rate for the mesial and distal areas compared with the vehicle-treated group. Thus, epileptic children who are treated over a long period with antiepileptics, especially at primary school age, should ensure good oral hygiene so as not to suffer bone loss, edentulism or gingival overgrowth. PMID:15672119

  18. The Role of Scaffold Architecture and Composition on the Bone Formation by Adipose-Derived Stem Cells

    PubMed Central

    Declercq, Heidi A.; Desmet, Tim; Dubruel, Peter

    2014-01-01

    Scaffold architecture and composition are crucial parameters determining the initial cell spatial distribution and consequently bone tissue formation. Three-dimensional poly-?-caprolactone (PCL) scaffolds with a 0/90° lay-down pattern were plotted and subjected to (1) an oxygen plasma (PCL O) or (2) a postargon plasma modification with gelatin and fibronectin (PCL Fn). These scaffolds with an open pore structure were compared with more compact scaffolds fabricated by conventional processing techniques: oxidized polylactic acid (LA O) and collagen (COL) scaffolds. Human adipose tissue-derived stem cell/scaffold interactions were studied. The study revealed that the biomimetic surface modification of plotted scaffolds did not increase the seeding efficiency. The proliferation and colonization was superior for PCL Fn in comparison with PCL O. The plotted PCL Fn was completely colonized throughout the scaffold, whereas conventional scaffolds only at the edge. Protein-based scaffolds (PCL Fn and COL) enhanced the differentiation, although plotted scaffolds showed a delay in their differentiation compared with compact scaffolds. In conclusion, protein modification of plotted PCL scaffolds enhances uniform tissue formation, but shows a delayed differentiation in comparison with compact scaffolds. The present study demonstrates that biomimetic PCL scaffolds could serve as a guiding template to obtain a uniform bone tissue formation in vivo. PMID:23998529

  19. FTY720 Promotes Local Microvascular Network Formation and Regeneration of Cranial Bone Defects

    PubMed Central

    Aronin, Caren E. Petrie; Sefcik, Lauren S.; Tholpady, Sunil S.; Tholpady, Ashok; Sadik, Karim W.; Macdonald, Timothy L.; Peirce, Shayn M.; Wamhoff, Brian R.; Lynch, Kevin R.; Ogle, Roy C.

    2010-01-01

    The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P1 and S1P3 significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P3 promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater. PMID:20038198

  20. Subcutaneous administration of insulin-like growth factor (IGF)-II/IGF binding protein-2 complex stimulates bone formation and prevents loss of bone mineral density in a rat model of disuse osteoporosis

    NASA Technical Reports Server (NTRS)

    Conover, Cheryl A.; Johnstone, Edward W.; Turner, Russell T.; Evans, Glenda L.; John Ballard, F. John; Doran, Patrick M.; Khosla, Sundeep

    2002-01-01

    Elevated serum levels of insulin-like growth factor binding protein-2 (IGFBP-2) and a precursor form of IGF-II are associated with marked increases in bone formation and skeletal mass in patients with hepatitis C-associated osteosclerosis. In vitro studies indicate that IGF-II in complex with IGFBP-2 has high affinity for bone matrix and is able to stimulate osteoblast proliferation. The purpose of this study was to determine the ability of the IGF-II/IGFBP-2 complex to increase bone mass in vivo. Osteopenia of the femur was induced by unilateral sciatic neurectomy in rats. At the time of surgery, 14-day osmotic minipumps containing vehicle or 2 microg IGF-II+9 microg IGFBP-2/100g body weight/day were implanted subcutaneously in the neck. Bone mineral density (BMD) measurements were taken the day of surgery and 14 days later using a PIXImus small animal densitometer. Neurectomy of the right hindlimb resulted in a 9% decrease in right femur BMD (P<0.05 vs. baseline). This loss in BMD was completely prevented by treatment with IGF-II/IGFBP-2. On the control limb, there was no loss of BMD over the 14 days and IGF-II/IGFBP-2 treatment resulted in a 9% increase in left femur BMD (P<0.05). Bone histomorphometry indicated increases in endocortical and cancellous bone formation rates and in trabecular thickness. These results demonstrate that short-term administration of the IGF-II/IGFBP-2 complex can prevent loss of BMD associated with disuse osteoporosis and stimulate bone formation in adult rats. Furthermore, they provide proof of concept for a novel anabolic approach to increasing bone mass in humans with osteoporosis.

  1. Nell-1 Protein Promotes Bone Formation in a Sheep Spinal Fusion Model

    PubMed Central

    Siu, Ronald K.; Lu, Steven S.; Li, Weiming; Whang, Julie; McNeill, Gabriel; Zhang, Xinli; Wu, Benjamin M.; Turner, A. Simon; Seim, Howard B.; Hoang, Paul; Wang, Jeffrey C.; Gertzman, Arthur A.; Ting, Kang

    2011-01-01

    Bone morphogenetic proteins (BMPs) are widely used as bone graft substitutes in spinal fusion, but are associated with numerous adverse effects. The growth factor Nel-like molecule-1 (Nell-1) is mechanistically distinct from BMPs and can minimize complications associated with BMP therapies. This study evaluates the efficacy of Nell-1 combined with demineralized bone matrix (DBM) as a novel bone graft material for interbody spine fusion using sheep, a phylogenetically advanced animal with biomechanical similarities to human spine. Nell-1+sheep DBM or Nell-1+heat-inactivated DBM (inDBM) (to determine the osteogenic effect of residual growth factors in DBM) were implanted in surgical sites as follows: (1) DBM only (control) (n=8); (2) DBM+0.3?mg/mL Nell-1 (n=8); (3) DBM+0.6?mg/mL Nell-1 (n=8); (4) inDBM only (control) (n=4); (5) inDBM+0.3?mg/mL Nell-1 (n=4); (6) inDBM+0.6?mg/mL Nell-1 (n=4). Fusion was assessed by computed tomography, microcomputed tomography, and histology. One hundred percent fusion was achieved by 3 months in the DBM+0.6?mg/mL Nell-1 group and by 4 months in the inDBM+0.6?mg/mL Nell-1 group; bone volume and mineral density were increased by 58% and 47%, respectively. These fusion rates are comparable to published reports on BMP-2 or autograft bone efficacy in sheep. Nell-1 is an independently potent osteogenic molecule that is efficacious and easily applied when combined with DBM. PMID:21128865

  2. 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 (?CT) 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 ?CT 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

  3. Alternaria keratitis after deep anterior lamellar keratoplasty.

    PubMed

    Naik, Mekhla; Mohd Shahbaaz; Sheth, Jay; Sunderamoorthy, S K

    2014-01-01

    To describe a case of Alternaria keratitis in a 30-year-old male patient who presented with bilateral vascularised central corneal opacity and underwent deep anterior lamellar keratoplasty (DALK) in the left eye. Patient was treated for recurrent epithelial defect with a bandage contact lens in the follow-up visits after DALK. Subsequently, patient presented with pigmented fungal keratitis, which on culture examination of the corneal scrapping demonstrated Alternaria species. Patient had to undergo a repeat DALK as the keratitis did not resolve with medical therapy alone. Patient did not have a recurrence for 11 months following the regraft. This case report highlights the importance of considering the Alternaria species as a possibile cause of non-resolving fungal keratitis after DALK. PMID:24669155

  4. Hydroxyapatite-poly(L-lactide) nanohybrids via surface-initiated ATRP for improving bone-like apatite-formation abilities

    NASA Astrophysics Data System (ADS)

    He, Jiqing; Yang, Xiaoping; Mao, Jiaofu; Xu, Fujian; Cai, Qing

    2012-07-01

    It is important to improve the compatibility of hydroxyapatite (HA) nanoparticles in biodegradable polyesters to obtain desirable nanocomposites for bone tissue engineering applications. Polymer grafting has been proven an efficient way to get nanohybrids with good dispersibility in polymeric matrixes. In this paper, a new strategy to prepare HA-poly(L-lactide) (PLLA) nanohybrids was developed, where PLLA oligomers were grafted from HA nanoparticle surfaces via surface-initiated atom transfer radical polymerization (ATRP) of methylacrylate group terminated PLLA macromonomers (PLLA-MA). HA with the derived ATRP initiators was obtained by (1) preparation of HA from precursors in the presence of 3-aminopropyl-triethoxysilane (APTS) to produce the HA surface with terminal sbnd NH2 groups (HA-NH2) and (2) reaction of the sbnd NH2 groups of the HA-NH2 nanoparticles with 2-bromoisobutyryl bromide (BIBB) to produce the 2-bromoisobutyryl-immobilized nanoparticles (HA-Br). The obtained HA-PLLA nanohybrids demonstrated good dispersibility in chloroform. With the good dispersion of HA-PLLA nanohybrids in PLLA matrix, the resultant PLLA/HA-PLLA nanocomposites could much faster induce bone-like apatite-formation in simulated body fluids (SBF) than the PLLA/HA counterparts where the HA nanoparticles aggregated heavily. With the versatility of ATRP, properly, grafting oligomeric PLLA chains from HA nanoparticle surfaces is an effective means for the design of novel HA-polymer biohybrids for future bone tissue engineering applications.

  5. Efficiency of High Molecular Weight Backbone Degradable HPMA Copolymer – Prostaglandin E1 Conjugate in Promotion of Bone Formation in Ovariectomized Rats

    PubMed Central

    Pan, Huaizhong; Sima, Monika; Miller, Scott C.; Kope?ková, Pavla; Yang, Jiyuan; Kope?ek, Jind?ich

    2013-01-01

    Multiblock, high molecular weight, linear, backbone degradable HPMA copolymer-prostaglandin E1 (PGE1) conjugate has been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA), which contains an enzymatically degradable oligopeptide sequence flanked by two dithiobenzoate groups, followed by post-polymerization aminolysis and thiol-ene chain extension. The multiblock conjugate contains Asp8 as the bone-targeting moiety and enzymatically degradable bonds in the polymer backbone; in vivo degradation produces cleavage products that are below the renal threshold. Using an ovariectomized (OVX) rat model, the accumulation in bone and efficacy to promote bone formation was evaluated; low molecular weight conjugates served as control. The results indicated a higher accumulation in bone, greater enhancement of bone density, and higher plasma osteocalcin levels for the backbone degradable conjugate. PMID:23731780

  6. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation

    E-print Network

    in these mice. SAMP6 mice have accelerated osteoporosis due to inadequate osteoblast renewal. Lithium lithium should determine whether it also improves bone mass in humans. anabolic osteoporosis therapy the Osteoporosis­Pseudoglioma syndrome (OPPG), an autosomal re- cessive disorder characterized by extremely low

  7. Low Magnitude and High Frequency Mechanical Loading Prevents Decreased Bone Formation Responses

    E-print Network

    to osteoporosis or disuse such as in paraplegia or microgravity is a significant health problem. As a treatment for osteoporosis, brief exposure of intact animals or humans to low magnitude and high frequency (LMHF) mechanical osteoporosis or disuse-induced bone loss. J. Cell. Biochem. 106: 306­ 316, 2009. ß 2009 Wiley-Liss, Inc. KEY

  8. Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation

    PubMed Central

    1994-01-01

    To elucidate the role of PTHrP in skeletal development, we examined the proximal tibial epiphysis and metaphysis of wild-type (PTHrP-normal) 18- 19-d-old fetal mice and of chondrodystrophic litter mates homozygous for a disrupted PTHrP allele generated via homologous recombination in embryonic stem cells (PTHrP-depleted). In the PTHrP-normal epiphysis, immunocytochemistry showed PTHrP to be localized in chondrocytes within the resting zone and at the junction between proliferative and hypertrophic zones. In PTHrP-depleted epiphyses, a diminished [3H]thymidine-labeling index was observed in the resting and proliferative zones accounting for reduced numbers of epiphyseal chondrocytes and for a thinner epiphyseal plate. In the mutant hypertrophic zone, enlarged chondrocytes were interspersed with clusters of cells that did not hypertrophy, but resembled resting or proliferative chondrocytes. Although the overall content of type II collagen in the epiphyseal plate was diminished, the lacunae of these non-hypertrophic chondrocytes did react for type II collagen. Moreover, cell membrane-associated chondroitin sulfate immunoreactivity was evident on these cells. Despite the presence of alkaline phosphatase activity on these nonhypertrophic chondrocytes, the adjacent cartilage matrix did not calcify and their persistence accounted for distorted chondrocyte columns and sporadic distribution of calcified cartilage. Consequently, in the metaphysis, bone deposited on the irregular and sparse scaffold of calcified cartilage and resulted in mixed spicules that did not parallel the longitudinal axis of the tibia and were, therefore, inappropriate for bone elongation. Thus, PTHrP appears to modulate both the proliferation and differentiation of chondrocytes and its absence alters the temporal and spatial sequence of epiphyseal cartilage development and of subsequent endochondral bone formation necessary for normal elongation of long bones. PMID:8089190

  9. Concave Pit-Containing Scaffold Surfaces Improve Stem Cell-Derived Osteoblast Performance and Lead to Significant Bone Tissue Formation

    PubMed Central

    Cusella-De Angelis, Maria Gabriella; Laino, Gregorio; Piattelli, Adriano; Pacifici, Maurizio; De Rosa, Alfredo; Papaccio, Gianpaolo

    2007-01-01

    Background Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear. Methodology and Findings In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i) large microcavities of 80–120 µm in diameter and 40–100 µm in depth, which we termed primary; and (ii) smaller microcavities of 10–20 µm in diameter and 3–10 µm in depth located within the primary cavities, which we termed secondary. We asked whether a microcavity-rich scaffold had distinct bone-forming capabilities compared to a smooth one. To do so, mesenchymal stem cells derived from human dental pulp were seeded onto the two types of scaffold and monitored over time for cytoarchitectural characteristics, differentiation status and production of important factors, including bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF). We found that the microcavity-rich scaffold enhanced cell adhesion: the cells created intimate contact with secondary microcavities and were polarized. These cytological responses were not seen with the smooth-surface scaffold. Moreover, cells on the microcavity-rich scaffold released larger amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline phosphatase activity. When this type of scaffold was transplanted into rats, superior bone formation was elicited compared to cells seeded on the smooth scaffold. Conclusion In conclusion, surface microcavities appear to support a more vigorous osteogenic response of stem cells and should be used in the design of therapeutic substrates to improve bone repair and bioengineering applications in the future. PMID:17551577

  10. Glucosamine and chondroitin sulfate association increases tibial epiphyseal growth plate proliferation and bone formation in ovariectomized rats

    PubMed Central

    Wolff, Roberta Bastos

    2014-01-01

    OBJECTIVE: The growth plate consists of organized hyaline cartilage and serves as a scaffold for endochondral ossification, a process that mediates longitudinal bone growth. Based on evidence showing that the oral administration of glucosamine sulfate (GS) and/or chondroitin sulfate (CS) is clinically valuable for the treatment of compromised articular cartilage, the current study evaluated the effects of these molecules on the tibial epiphyseal growth plate in female rats. METHOD: The animals were divided into two control groups, including vehicle treatment for 45 days (GC45) and 60 days (GC60) and six ovariectomized (OVX) groups, including vehicle treatment for 45 days (GV45), GS for 45 days (GE45GS), GS+CS for 45 days (GE45GS+CS), vehicle for 60 days (GV60), GS for 60 days (GE60GS) and GS+CS for 60 days (GE60GS+CS). At the end of treatment, the tibias were dissected, decalcified and processed for paraffin embedding. Morphological and morphometric methods were employed for analyzing the distal tibial growth plates using picrosirius red staining and the samples were processed for histochemical hyaluronan detection. Morphometric analyses were performed using the 6.0ProPlus® Image system. RESULTS: Notably, after 60 days of treatment, the number of proliferative chondrocytes increased two-fold, the percentage of remaining cartilage increased four-fold and the percentage of trabecular bone increased three-fold in comparison to the control animals. CONCLUSION: GS and CS treatment drugs led to marked cellular proliferation of the growth plate and bone formation, showing that drug targeting of the tibial epiphyseal growth plate promoted longitudinal bone growth. PMID:25627998

  11. Insight into the transgenerational effect of benzo[a]pyrene on bone formation in a teleost fish (Oryzias latipes).

    PubMed

    Seemann, Frauke; Peterson, Drew R; Witten, P Eckhard; Guo, Bao-Sheng; Shanthanagouda, Adamane H; Ye, Rui R; Zhang, Ge; Au, Doris W T

    2015-12-01

    Recent cross-generational studies in teleost fish have raised the awareness that high levels of benzo[a]pyrene (BaP) could affect skeletal integrity in the directly exposed F0 and their F1-F2. However, no further details were provided about the causes for abnormalities on the molecular and cellular level and the persistence of such sub-organismal impairments at the transgenerational scale (beyond F2). Adult Oryzias latipes were exposed to 1?g/L BaP for 21days. The F1-F3 were examined for skeletal deformities, histopathological alterations of vertebral bodies and differential expression of key genes of bone metabolism. Significant increase of dorsal-ventral vertebral compression was evident in ancestrally exposed larvae. Histopathological analysis revealed abnormal loss of notochord sheath, a lack of notochord epithelial integrity, reduced bone tissue and decreased osteoblast abundance. A significant downregulation of ATF4 and/or osterix and a high biological variability of COL10, coupled with a significant deregulation of SOX9a/b in the F1-F3 suggest that ancestral BaP exposure most likely perturbed chordoblasts, chondroblast and osteoblast differentiation, resulting in defective notochord sheath repair and rendering the vertebral column more vulnerable to compression. The present findings provide novel molecular and cellular insights into BaP-induced transgenerational bone impairment in the unexposed F3. From the ecological risk assessment perspective, BaP needs to be regarded as a transgenerational skeletal toxicant, which exerts a far-reaching impact on fish survival and fitness. Given that basic mechanisms of cartilage/bone formation are conserved between medaka and mammals, the results may also shed light on the potential transgenerational effect of BaP on the genesis of skeletal diseases in humans. PMID:26456900

  12. Bone Marrow-Derived Matrix Metalloproteinase-9 Is Associated with Fibrous Adhesion Formation after Murine Flexor Tendon Injury

    PubMed Central

    Loiselle, Alayna E.; Frisch, Benjamin J.; Wolenski, Matthew; Jacobson, Justin A.; Calvi, Laura M.; Schwarz, Edward M.; Awad, Hani A.; O’Keefe, Regis J.

    2012-01-01

    The pathogenesis of adhesions following primary tendon repair is poorly understood, but is thought to involve dysregulation of matrix metalloproteinases (Mmps). We have previously demonstrated that Mmp9 gene expression is increased during the inflammatory phase following murine flexor digitorum (FDL) tendon repair in association with increased adhesions. To further investigate the role of Mmp9, the cellular, molecular, and biomechanical features of healing were examined in WT and Mmp9?/? mice using the FDL tendon repair model. Adhesions persisted in WT, but were reduced in Mmp9?/? mice by 21 days without any decrease in strength. Deletion of Mmp9 resulted in accelerated expression of neo-tendon associated genes, Gdf5 and Smad8, and delayed expression of collagen I and collagen III. Furthermore, WT bone marrow cells (GFP+) migrated specifically to the tendon repair site. Transplanting myeloablated Mmp9?/? mice with WT marrow cells resulted in greater adhesions than observed in Mmp9?/? mice and similar to those seen in WT mice. These studies show that Mmp9 is primarily derived from bone marrow cells that migrate to the repair site, and mediates adhesion formation in injured tendons. Mmp9 is a potential target to limit adhesion formation in tendon healing. PMID:22792383

  13. Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice

    PubMed Central

    Yan, Wei; Wang, Ting-yu; Fan, Qi-ming; Du, Lin; Xu, Jia-ke; Zhai, Zan-jing; Li, Hao-wei; Tang, Ting-ting

    2014-01-01

    Aim: To investigate the effects of plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica, on human breast cancer cell growth and the cancer cell-induced osteolysis in the bone microenvironment of mice. Methods: Human breast cancer cell subline MDA-MB-231SA with the ability to spread and grow in the bone was tested. The cell proliferation was determined using the CCK-8 assay. Apoptosis was detected with Annexin V/PI double-labeled flow cytometry. Red fluorescent protein-labeled MDA-MB-231SArfp cells were injected into the right tibia of female BALB/c-nu/nu mice. Three days after the inoculation, the mice were injected with plumbagin (2, 4, or 6 mg/kg, ip) 5 times per week for 7 weeks. The growth of the tumor cells was monitored using an in vivo imaging system. After the mice were sacrificed, the hind limbs were removed for radiographic and histological analyses. Results: Plumbagin (2.5–20 ?mol/L) concentration-dependently inhibited the cell viability and induced apoptosis of MDA-MB-231SA cells in vitro (the IC50 value of inhibition of cell viability was 14.7 ?mol/L). Administration of plumbagin to breast cancer bearing mice delayed the tumor growth by 2–3 weeks and reduced the tumor volume by 44%–74%. The in vivo imaging study showed that plumbagin dose-dependently inhibited MDA-MB-231SArfp cell growth in bone microenvironment. Furthermore, X-ray images and micro-CT study demonstrated that plumbagin reduced bone erosion area and prevented a decrease in bone tissue volume. Histological studies showed that plumbagin dose-dependently inhibited the breast cancer cell growth, enhanced the cell apoptosis and reduced the number of TRAcP-positive osteoclasts. Conclusion: Plumbagin inhibits the cell growth and induces apoptosis in human breast cancer cells in mice bone microenvironment, leading to significant reduction in osteolytic lesions caused by the tumor cells. PMID:24384612

  14. Lamellar Diblock Copolymers on Rough Substrates: Self-consistent Field Theory Studies

    E-print Network

    Xingkun Man; Jiuzhou Tang; Pan Zhou; Dadong Yan; David Andelman

    2015-08-18

    We present numerical calculations of lamellar phases of di-block copolymers (BCP) confined between two surfaces, where the top surface is flat and the bottom one is corrugated. The corrugated substrate is assumed to have a single $q$-mode of lateral undulations with a wavenumber q_s and amplitude R. We focus on the effects of substrate roughness, parameterized by the dimensionless quantity, q_sR, on the relative stability between parallel and perpendicular orientations of the lamellar phase. The competition between film confinement, energy cost of elastic deformation and gain in surface energy induces a parallel-to-perpendicular transition of the BCP lamellae. Employing self-consistent field theory (SCFT), we study the critical substrate roughness value corresponding to this transition. The critical value increases as function of the surface preference towards one of the two BCP components, and as function of film thickness. But, it decreases with increasing values of the Flory-Huggins parameter. Our findings are equivalent to stating that the critical value decreases as the BCP molecular weight or the natural BCP periodicity increases. We further show that the rough substrate can overcome the formation of parallel lamellae in cases where the top surface has a preference towards one of the two BCP components. Our results are in good agreement with previous experiments, and highlight the physical conditions behind the perpendicular orientation of lamellar phases, as is desired in nanolithography and other industrial applications.

  15. In vitro and in vivo endochondral bone formation models allow identification of anti-angiogenic compounds.

    PubMed

    van der Pluijm, Gabri; Deckers, Martine; Sijmons, Bianca; de Groot, Henny; Bird, John; Wills, Ruth; Papapoulos, Socrates; Baxter, Andy; Löwik, Clemens

    2003-07-01

    A major obstacle in the study of angiogenesis and the testing of new agents with anti-angiogenic potential has been the lack of experimental models with predictive in vivo value. We describe here the combined use of in vitro and in vivo angiogenesis models that are based on endochondral bone development. This approach led to the identification of a new inhibitor of matrix metalloprotease (MMP) activity that inhibits neovascularization in vitro and in vivo while osteoclast invasion, which occurs simultaneously during bone development, remained unaffected. In contrast, the broad-spectrum MMP-inhibitor marimastat inhibited both in vitro angiogenesis and osteoclastogenesis dose-dependently but displayed severe toxic side effects in vivo. The combined use of these experimental models may, therefore, facilitate the discovery of mechanisms underlying angiogenesis and lead to identification of new pharmacological compounds with clinical efficacy and appropriate selectivity in the treatment of angiogenesis-dependent disorders like arthritis and cancer. PMID:12819020

  16. Diffuse idiopathic skeletal hyperostosis with prominent appendicular bone proliferation in a dog

    PubMed Central

    OH, Juyeon; LEE, Ju-Hwan; CHO, Kyoung-Oh; CHOI, Jihye

    2015-01-01

    This report described radiographic and CT features of atypical diffuse idiopathic skeletal hyperostosis in a 5 year-old, female Shih-tzu showing marked proliferative bone lesions in the appendicular skeleton with minor spinal changes. Continuous or flowing bony bridge formation of vertebrae is used as the gold standard for diagnosing diffuse idiopathic skeletal hyperostosis. However, this criterion seems not to be suitable for appendicular type diffuse idiopathic skeletal hyperostosis, as in the present case. Diffuse idiopathic skeletal hyperostosis is a progressive skeletal disease, and thus, enthesophytosis and the multiple bony proliferations at insertion sites of ligaments and tendons to appendicular bones in a lamellar or trabecular pattern were considered diagnostic features of the appendicular type of diffuse idiopathic skeletal hyperostosis. PMID:25648674

  17. Histological evaluation of a biomimetic material in bone regeneration after one year from graft

    PubMed Central

    Figliuzzi, Michele M.; De Fazio, Rossella; Tiano, Rosamaria; De Franceschi, Serena; Pacifico, Delfina; Mangano, Francesco; Fortunato, Leonzio

    2014-01-01

    Summary Aim The use of substitute materials is one of the solutions used in periodontology for the reconstruction of intrabony defects. Advances in scientific research gave rise to a new generation of biomaterials of synthetic origin stoichiometrically unstable and therefore really absorbable. Our research is directed precisely towards a biomaterial synthesis, Engipore® (Finceramica, Faenza, Italy) which is a bone substitute of the latest hydroxyapatite-based generation, that possesses chemical and morphological properties similar to those of natural bone in the treatment of infrabony periodontal defects. Aim of this study was to evaluate the efficacy of Engipore® in the treatment of intrabony periodontal defects. Methods The study was conducted on 100 parodontopatics patients, which had gingival pockets of at least infrabonies 8/10 mm. The histological evaluation was performed with samples after one year from the graft. Results The histological samples collected after one year showed an abundant new bone formation, with mature lamellar bone tissue surrounding the residual particles of Engipore® that appear completely osteointegrated. The surrounding connective tissue shows no signs of inflammation. Conclusions The results obtained in our research demonstrated that, after a proper selection of patients and lesions, and applying an adequate surgical technique, this type of biomaterial in the treatment of periodontal defects acts in an optimal manner as a filler inducing the formation of new bone as evidenced by histological examinations. PMID:25506415

  18. Endochondral bone formation in toothless (osteopetrotic) rats: failures of chondrocyte patterning and type X collagen expression.

    PubMed

    Marks, S C; Lundmark, C; Christersson, C; Wurtz, T; Odgren, P R; Seifert, M F; Mackay, C A; Mason-Savas, A; Popoff, S N

    2000-04-01

    The pacemaker of endochondral bone growth is cell division and hypertrophy of chondrocytes. The developmental stages of chondrocytes, characterized by the expression of collagen types II and X, are arranged in arrays across the growth zone. Mutations in collagen II and X genes as well as the absence of their gene products lead to different, altered patterns of chondrocyte stages which remain aligned across the growth plate (GP). Here we analyze GP of rats bearing the mutation toothless (tl) which, apart from bone defects, develop a progressive, severe chondrodystrophy during postnatal weeks 3 to 6. Mutant GP exhibited disorganized, non-aligned chondrocytes and mineralized metaphyseal bone but without cartilage mineralization or cartilaginous extensions into the metaphysis. Expression of mRNA coding for collagen types II (Col II) and X (Col X) was examined in the tibial GP by in situ hybridization. Mutant rats at 2 weeks exhibited Col II RNA expression and some hypertrophied chondrocytes (HC) but no Col X RNA was detected. By 3rd week, HC had largely disappeared from the central part of the mutant GP and Col II RNA expression was present but weak and in 2 separate bands. Peripherally the GP contained HC but without Col X RNA expression. This abnormal pattern was exacerbated by the fourth week. Bone mineralized but cartilage in the GP did not. These data suggest that the tl mutation involves a regulatory function for chondrocyte maturation, including Col X RNA synthesis and mineralization, and that the GP abnormalities are related to the Col X deficiency. The differences in patterning in the tl rat GP compared to direct Col X mutations may be explained by compensatory effects. PMID:10853827

  19. Regulation of bone formation by baicalein via the mTORC1 pathway

    PubMed Central

    Li, Sheng-fa; Tang, Jia-jun; Chen, Jian; Zhang, Pei; Wang, Ting; Chen, Tian-yu; Yan, Bo; Huang, Bin; Wang, Liang; Huang, Min-jun; Zhang, Zhong-min; Jin, Da-di

    2015-01-01

    Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 ?mol/L, 1 ?mol/L, 10 ?mol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen I?1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1. PMID:26392752

  20. Magnetic Nanorods Confined in a Lamellar Lyotropic Phase

    E-print Network

    Keevin Béneut; Doru Constantin; Patrick Davidson; Arnaud Dessombz; Corinne Chanéac

    2015-04-11

    The dilute lamellar phase of the nonionic surfactant C$_{12}$EO$_5$ was doped with goethite (iron oxide) nanorods up to a fraction of 5 vol. %. The interaction between the inclusions and the host phase was studied by polarized optical microscopy (with or without an applied magnetic field) and by small-angle X-ray scattering. We find that, when the orientation of the nanorods is modified using the magnetic field, the texture of the lamellar phase changes accordingly; one can thus induce a homeotropic-planar reorientation transition. On the other hand, the lamellar phase induces an attractive interaction between the nanorods. In more concentrated lamellar phases (under stronger confinement) the particles form aggregates. This behavior is not encountered for a similar system doped with spherical particles, emphasizing the role of particle shape in the interaction between doping particles and the host phase.

  1. Osteoblast-Specific Loss of IGF1R Signaling Results in Impaired Endochondral Bone Formation During Fracture Healing.

    PubMed

    Wang, Tao; Wang, Yongmei; Menendez, Alicia; Fong, Chak; Babey, Muriel; Tahimic, Candice G T; Cheng, Zhiqiang; Li, Alfred; Chang, Wenhan; Bikle, Daniel D

    2015-09-01

    Insulin-like growth factors (IGFs) are important local regulators during fracture healing. Although IGF1 deficiency is known to increase the risk of delayed union or non-union fractures in the elderly population, the underlying mechanisms that contribute to this defect remains unclear. In this study, IGF1 signaling during fracture healing was investigated in an osteoblast-specific IGF1 receptor (IGF1R) conditional knockout (KO) mouse model. A closed tibial fracture was induced in IGF1R(flox/flox) /2.3-kb ?1(1)-collagen-Cre (KO) and IGF1R(flox/flox) (control) mice aged 12 weeks. Fracture callus samples and nonfractured tibial diaphysis were collected and analyzed by ?CT, histology, immunohistochemistry, histomorphometry, and gene expression analysis at 10, 15, 21, and 28 days after fracture. A smaller size callus, lower bone volume accompanied by a defect in mineralization, bone microarchitectural abnormalities, and a higher cartilage volume were observed in the callus of these KO mice. The levels of osteoblast differentiation markers (osteocalcin, alkaline phosphatase, collagen 1?1) were significantly reduced, but the early osteoblast transcription factor runx2, as well as chondrocyte differentiation markers (collagen 2?1 and collagen 10?1) were significantly increased in the KO callus. Moreover, increased numbers of osteoclasts and impaired angiogenesis were observed during the first 15 days of fracture repair, but decreased numbers of osteoclasts were found in the later stages of fracture repair in the KO mice. Although baseline nonfractured tibias of KO mice had decreased trabecular and cortical bone compared to control mice, subsequent studies with mice expressing the 2.3-kb ?1(1)-collagen-Cre ERT2 construct and given tamoxifen at the time of fracture and so starting with comparable bone levels showed similar impairment in fracture repair at least initially. Our data indicate that not only is the IGF1R in osteoblasts involved in osteoblast differentiation during fracture repair, but it plays an important role in coordinating chondrocyte, osteoclast, and endothelial responses that all contribute to the endochondral bone formation required for normal fracture repair. PMID:25801198

  2. Personalised lamellar keratoplasty and keratopigmentation in Asian corneal leucoma patients

    PubMed Central

    Liu, Xin; Shen, Jun-Hui; Zhou, Qi; Liu, Zhen-Xing; Tang, Shen-Fei; Chen, Ran-Ran; Sui, Gui-Qin; Bi, Yan-Long

    2015-01-01

    Objective: To describe a personalised lamellar keratoplasty (LK) associated with the keratopigmentation (KTP) technique for corneal leucoma among Asian patients. Methods: This report was a non-randomised, retrospective clinical study performed in 32 consecutive eyes of 32 patients to improve cosmetic appearance. Twenty-two patients underwent LK combined with KTP, either by intralamellar or superficial route. Ten patients underwent the single personalised keratopigmentation method. The subjective and objective cosmetic results, ocular irritation, colour fading, neovascularisation formation and incidence of immune rejection were evaluated until three years after surgery. Results: No complications occurred, and the corneal leucoma was successfully stained with India ink in all 32 patients. Most of the patients showed good cosmetic appearance. Pain, conjunctival congestion, corneal edema and foreign body sensation disappeared gradually within two to three weeks after surgery in all patients. Graft swelling, non-healing, or detaching was not observed during follow-up. However, two patients had slight opacity three years after LK. Colour fading was observed in one patient who underwent intralamellar corneal staining 10 months after surgery. Re-staining was performed. Conclusion: KTP combined with personalised LK is an effective personalised technique that presents long-standing colour staining and good cosmetic efficacy. PMID:26309607

  3. Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q

    SciTech Connect

    Russell, L.J.; Compton, J.G.; Bale, S.J.; DiGiovanna, J.J.; Hashem, N.

    1994-12-01

    The authors have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.

  4. Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression

    PubMed Central

    Yoshimatsu, Yasuhiro; Lee, Yulia G.; Akatsu, Yuichi; Taguchi, Luna; Suzuki, Hiroshi I.; Cunha, Sara I.; Maruyama, Kazuichi; Suzuki, Yuka; Yamazaki, Tomoko; Katsura, Akihiro; Oh, S. Paul; Zimmers, Teresa A.; Lee, Se-Jin; Pietras, Kristian; Koh, Gou Young; Miyazono, Kohei; Watabe, Tetsuro

    2013-01-01

    Lymphatic vessels (LVs) play critical roles in the maintenance of fluid homeostasis and in pathological conditions, including cancer metastasis. Although mutations in ALK1, a member of the transforming growth factor (TGF)-?/bone morphogenetic protein (BMP) receptor family, have been linked to hereditary hemorrhagic telangiectasia, a human vascular disease, the roles of activin receptor-like kinase 1 (ALK-1) signals in LV formation largely remain to be elucidated. We show that ALK-1 signals inhibit LV formation, and LVs were enlarged in multiple organs in Alk1-depleted mice. These inhibitory effects of ALK-1 signaling were mediated by BMP-9, which decreased the number of cultured lymphatic endothelial cells. Bmp9-deficient mouse embryos consistently exhibited enlarged dermal LVs. BMP-9 also inhibited LV formation during inflammation and tumorigenesis. BMP-9 downregulated the expression of the transcription factor prospero-related homeobox 1, which is necessary to maintain lymphatic endothelial cell identity. Furthermore, silencing prospero-related homeobox 1 expression inhibited lymphatic endothelial cell proliferation. Our findings reveal a unique molecular basis for the physiological and pathological roles of BMP-9/ALK-1 signals in LV formation. PMID:24133138

  5. Integrated miRNA and mRNA expression profiling of tension force-induced bone formation in periodontal ligament cells.

    PubMed

    Chang, Maolin; Lin, Heng; Luo, Meng; Wang, Jie; Han, Guangli

    2015-09-01

    Tension force-induced bone formation is a complex biological process altered by various factors, for example miRNAs and gene regulatory network. However, we know little about critical gene regulators and their functional consequences on this complex process. The aim of this study was to determine the integrated relation between microRNA and mRNA expression in tension force-induced bone formation in periodontal ligament cells by a system biological approach. We identified 818 mRNAs and 32 miRNAs differentially expressed between cyclic tension force-stimulated human periodontal ligament cells and control cells by microarrays. By using miRNA/mRNA network analysis, protein-protein interactions network analysis, and hub analysis, we found that miR-195-5p, miR-424-5p, miR-1297, miR-3607-5p, miR-145-5p, miR-4328, and miR-224-5p were core microRNAs of tension force-induced bone formation. WDR33, HSPH1, ERBB3, RIF1, IKBKB, CREB1, FGF2, and PAG1 were identified as hubs of the PPI network, suggesting the biological significance in this process. The miRNA expression was further examined in human PDLC and animal samples by using quantitative real-time PCR. Thus, we proposed a model of tension force-induced bone formation which is co-regulated through integration of the miRNA and mRNA. This study illustrated the benefits of system biological approaches in the analysis of tension force-induced bone formation as a complex biological process. We used public information and our experimental data to do comprehensive analysis and revealed the coordination transcriptional control of miRNAs of tension force-induced bone formation. PMID:26091625

  6. Shear-Induced Collapse in a Lyotropic Lamellar Phase

    NASA Astrophysics Data System (ADS)

    Porcar, L.; Warr, G. G.; Hamilton, W. A.; Butler, P. D.

    2005-08-01

    An entropically stabilized cetylpyridinium chloride, hexanol, and heavy brine lyotropic lamellar phase subjected to shear flow has been observed here by small angle neutron scattering to undergo collapse of smectic order above a threshold shear rate. The results are compared with theories predicting that such a lamellar phase sheared above a critical rate should lose its stability by a loss of resistance to compression due to the suppression of membrane fluctuations.

  7. Shear-Induced Collapse in a Lyotropic Lamellar Phase

    SciTech Connect

    Porcar, L.; Warr, G.G.; Hamilton, W.A.; Butler, P.D.

    2005-08-12

    An entropically stabilized cetylpyridinium chloride, hexanol, and heavy brine lyotropic lamellar phase subjected to shear flow has been observed here by small angle neutron scattering to undergo collapse of smectic order above a threshold shear rate. The results are compared with theories predicting that such a lamellar phase sheared above a critical rate should lose its stability by a loss of resistance to compression due to the suppression of membrane fluctuations.

  8. Probable Ankylosaur Ossicles from the Middle Cenomanian Dunvegan Formation of Northwestern Alberta, Canada

    PubMed Central

    Burns, Michael E.; Vavrek, Matthew J.

    2014-01-01

    A sample of six probable fragmentary ankylosaur ossicles, collected from Cenomanian deposits of the Dunvegan Formation along the Peace River, represent one of the first dinosaurian skeletal fossils reported from pre-Santonian deposits in Alberta. Specimens were identified as ankylosaur by means of a palaeohistological analysis. The primary tissue is composed of zonal interwoven structural fibre bundles with irregularly-shaped lacunae, unlike the elongate lacunae of the secondary lamellar bone. The locality represents the most northerly Cenomanian occurrence of ankylosaur skeletal remains. Further fieldwork in under-examined areas of the province carries potential for additional finds. PMID:24816807

  9. Effects of Cell-Attachment and Extracellular Matrix on Bone Formation In Vivo in Collagen-Hydroxyapatite Scaffolds

    PubMed Central

    Villa, Max M.; Wang, Liping; Rowe, David W.; Wei, Mei

    2014-01-01

    Cell-based tissue engineering can be used to replace missing or damaged bone, but the optimal methods for delivering therapeutic cells to a bony defect have not yet been established. Using transgenic reporter cells as a donor source, two different collagen-hydroxyapatite (HA) scaffolds, and a critical-size calvarial defect model, we investigated the effect of a cell-attachment period prior to implantation, with or without an extracellular matrix-based seeding suspension, on cell engraftment and osteogenesis. When quantitatively compared, the in-house scaffold implanted immediately had a higher mean radiopacity than in-house scaffolds incubated overnight. Both scaffold types implanted immediately had significantly higher area fractions of donor cells, while the in-house collagen-HA scaffolds implanted immediately had higher area fractions of the mineralization label compared with groups incubated overnight. When the cell loading was compared in vitro for each delivery method using the in-house scaffold, immediate loading led to higher numbers of delivered cells. Immediate loading may be preferable in order to ensure robust bone formation in vivo. The use of a secondary ECM carrier improved the distribution of donor cells only when a pre-attachment period was applied. These results have improved our understanding of cell delivery to bony defects in the context of in vivo outcomes. PMID:25329879

  10. Effects of Glucosinolates from Turnip (Brassica rapa L.) Root on Bone Formation by Human Osteoblast-Like MG-63 Cells and in Normal Young Rats.

    PubMed

    Jeong, Jaehoon; Park, Heajin; Hyun, Hanbit; Kim, Jihye; Kim, Haesung; Oh, Hyun Il; Hwang, Hye Seong; Kim, Dae Kyong; Kim, Ha Hyung

    2015-06-01

    Turnip (Brassica rapa L.) root ethanol extract (TRE) was prepared, and its chemical constituents were characterized by ultra-performance liquid chromatography and mass spectrometry. Thirteen glucosinolates (GSLs) were identified, comprising eight aliphatic, four indolic, and one aromatic compounds. The effects of these GSLs on bone formation were investigated in vitro by incubating human osteoblast-like MG-63 cells with TRE and then analyzing their viability, alkaline phosphatase (ALP) activity, collagen content, and mineralization and in vivo by administering TRE orally to normal young rats (500?mg/kg/day) and assessing subsequent changes in serum osteocalcin and bone microstructure in these animals. No TRE-related toxicity was found, and the levels of cell viability, ALP activity, collagen synthesis, and mineralization were significantly increased relative to the negative control. In particular, stimulatory effects on the differentiation of MG-63 cells were strongly enhanced as compared with a positive control (daidzein). Serum osteocalcin was also significantly increased, and some important bone microstructural parameters were improved in TRE-administered rats compared with their saline-administered counterparts. GSLs therefore appear to have a stimulatory effect on bone formation in both MG-63 cells and normal young rats. This is the first report on the usefulness of turnip root and its GSL compounds for bone formation. PMID:25809011

  11. Bone morphogenetic protein 2 promotes primordial follicle formation in the ovary

    PubMed Central

    Chakraborty, Prabuddha; Roy, Shyamal K.

    2015-01-01

    Primordial follicles (PF) are formed when somatic cells differentiate into flattened pregranulosa cells, invaginate into the oocyte nests and encircle individual oocytes. We hypothesize that BMP2 regulates PF formation by promoting the transition of germ cells into oocytes and somatic cells into pregranulosa cells. E15 hamster ovaries were cultured for 8 days corresponding to postnatal day 8 (P8) in vivo, with or without BMP2, and the formation of PF was examined. BMP2 was expressed in the oocytes as well as ovarian somatic cells during development. BMP2 exposure for the first two days or the last two days or the entire 8 days of culture led to increase in PF formation suggesting that BMP2 affected both germ cell transition and somatic cell differentiation. Whereas an ALK2/3 inhibitor completely blocked BMP2-induced PF formation, an ALK2-specific inhibitor was partially effective, suggesting that BMP2 affected PF formation via both ALK2 and ALK3. BMP2 also reduced apoptosis in vitro. Further, more meiotic oocytes were present in BMP2 exposed ovaries. In summary, the results provide the first evidence that BMP2 regulates primordial follicle formation by promoting germ cell to oocyte transition and somatic cell to pre-granulosa cells formation and it acts via both ALK2 and ALK3. PMID:26219655

  12. 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 17?-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

  13. Evolutionary Patterns of Bone Histology and Bone Compactness in Xenarthran Mammal Long Bones

    PubMed Central

    Straehl, Fiona R.; Scheyer, Torsten M.; Forasiepi, Analía M.; MacPhee, Ross D.; Sánchez-Villagra, Marcelo R.

    2013-01-01

    Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness. PMID:23874932

  14. Evolutionary patterns of bone histology and bone compactness in xenarthran mammal long bones.

    PubMed

    Straehl, Fiona R; Scheyer, Torsten M; Forasiepi, Analía M; MacPhee, Ross D; Sánchez-Villagra, Marcelo R

    2013-01-01

    Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness. PMID:23874932

  15. Author's personal copy Rolling bones Taphonomy of Jurassic dinosaur bones inferred from diagenetic

    E-print Network

    Schöne, Bernd R.

    Author's personal copy Rolling bones ­ Taphonomy of Jurassic dinosaur bones inferred from 2010 Accepted 28 January 2011 Available online 4 February 2011 Keywords: Dinosaurs Taphonomy Diagenesis Bone histology Pyrolusite Junggar Basin Dinosaur bones from the Upper Jurassic Shishugou Formation near

  16. Icariin Augments Bone Formation and Reverses the Phenotypes of Osteoprotegerin-Deficient Mice through the Activation of Wnt/?-Catenin-BMP Signaling

    PubMed Central

    Li, Xiao-Feng; Xu, Hao; Zhao, Yong-Jian; Tang, De-Zhi; Xu, Guo-Hua; Holz, Jonathan; Wang, Jing; Cheng, Shao-Dan; Shi, Qi; Wang, Yong-Jun

    2013-01-01

    Icariin has been mostly reported to enhance bone fracture healing and treat postmenopausal osteoporosis in ovariectomized animal model. As another novel animal model of osteoporosis, there is few publication about the effect of Icariin on osteoprotegerin-deficient mice. Therefore, the goal of this study is to find the effect on bone formation and underlying mechanisms of Icariin in osteoprotegerin (OPG) knockout (KO) mice. We found that Icariin significantly stimulated new bone formation after local injection over the surface of calvaria at the dose of 5?mg/kg per day. With this dose, Icariin was also capable of significantly reversing OPG-deficient-induced bone loss and bone strength reduction. Real-time PCR analysis showed that Icariin significantly upregulated the expression of BMP2, BMP4, RUNX2, OC, Wnt1, and Wnt3a in OPG KO mice. Icariin also significantly increased the expression of AXIN2, DKK1, TCF1, and LEF1, which are the direct target genes of ?-catenin signaling. The in vitro studies showed that Icariin induced osteoblast differentiation through the activation of Wnt/?-catenin-BMP signaling by in vitro deletion of the ?-catenin gene using ?-cateninfx/fx mice. Together, our findings demonstrate that Icariin significantly reverses the phenotypes of OPG-deficient mice through the activation of Wnt/?-catenin-BMP signaling. PMID:24348713

  17. Tissue growth controlled by geometric boundary conditions: a simple model recapitulating aspects of callus formation and bone healing.

    PubMed

    Fischer, F Dieter; Zickler, Gerald A; Dunlop, John W C; Fratzl, Peter

    2015-06-01

    The shape of tissues arises from a subtle interplay between biochemical driving forces, leading to cell growth, division and extracellular matrix formation, and the physical constraints of the surrounding environment, giving rise to mechanical signals for the cells. Despite the inherent complexity of such systems, much can still be learnt by treating tissues that constantly remodel as simple fluids. In this approach, remodelling relaxes all internal stresses except for the pressure which is counterbalanced by the surface stress. Our model is used to investigate how wettable substrates influence the stability of tissue nodules. It turns out for a growing tissue nodule in free space, the model predicts only two states: either the tissue shrinks and disappears, or it keeps growing indefinitely. However, as soon as the tissue wets a substrate, stable equilibrium configurations become possible. Furthermore, by investigating more complex substrate geometries, such as tissue growing at the end of a hollow cylinder, we see features reminiscent of healing processes in long bones, such as the existence of a critical gap size above which healing does not occur. Despite its simplicity, the model may be useful in describing various aspects related to tissue growth, including biofilm formation and cancer metastases. PMID:26018964

  18. Influence of interimplant distance on papilla formation and bone resorption: a clinical-radiographic study in dogs.

    PubMed

    de Oliveira, Rafael R; Novaes, Arthur B; Papalexiou, Vula; Muglia, Valdir A; Taba, Mário

    2006-01-01

    Implant esthetics has been the focus of attention for the past decade, and one vital issue is the effect of interimplant distance on interimplant papilla formation and crestal bone loss. The aim of this study was to evaluate the effect of 1, 2, and 3 mm of interimplant distance on papilla formation and crestal resorption in submerged and nonsubmerged Ankylos implants after prosthetic restoration. Bilateral mandibular premolars of 7 dogs were extracted, and after 12 weeks each dog received 8 implants. Implants were placed so that 3 interimplant distances were created at 1 mm (group 1), 2 mm (group 2), and 3 mm (group 3). The sides and the position of the groups were randomly selected. Twelve weeks after placement, the implants received metallic prostheses that allowed 5 mm of space between the prosthetic contact point (CP) and the crestal bone (CB). After 8 weeks, the distance between the CP and the papilla (CP-P) and the gingival height at the distal proximal aspect of the prosthesis (CP-DE) was clinically measured. Radiographic images were obtained to measure the distance of the CP to the CB within the interimplant surfaces (CP-IP) and adjacent to the edentulous surfaces (CP-ED). The clinical measurement of CP-P for submerged and nonsubmerged implants was 3.57+/-1.17 mm and 3.10+/-0.82 mm for group 1, 3.57+/-0.78 mm and 3.16+/- 0.87 mm for group 2, and 3.35+/- 0.55 mm and 3.07+/-0.93 mm for group 3. The CP-DE was 3.25+/-0.77 mm for submerged and 2.78+/- 0.64 mm for nonsubmerged implants. The CP-IP for the submerged and nonsubmerged implants was 6.91+/-0.95 mm and 7.68+/-2.73 mm for group 1, 7.46+/-1.43 mm and 5.87+/-1.71 mm for group 2, and 7.72+/-0.81 mm and 7.59+/-1.33 mm for group 3. The CP-ED was 6.77+/-1.33 mm for submerged implants and 6.03+/-1.58 mm for nonsubmerged implants. There were no statistical significant differences for any of the measured parameters. We conclude that when the distance from the CP to the CB was 5 mm, interimplant distances of 1 to 3 mm did not affect papilla formation or crestal resorption of submerged or nonsubmerged implants in the dog model. PMID:17069166

  19. Effect of mineral-collagen interfacial behavior on the microdamage progression in bone using a probabilistic cohesive finite element model.

    PubMed

    Luo, Qing; Nakade, Rugved; Dong, Xuanliang; Rong, Qiguo; Wang, Xiaodu

    2011-10-01

    The interactions between mineral and collagen phases in the ultrastructural level play an important role in determining the mechanical properties of bone tissue. Three types of mineral-collagen interaction (i.e., ionic interactions, hydrogen/van der Waals bonds, and van der Waals/viscous shear in opening/sliding mode, respectively) have been simulated in this study, using cohesive zone-modeling techniques. Considering the inhomogeneity of bone, a probabilistic failure analysis approach has been also employed to account for the effect of mineral-collagen interfacial behavior on microdamage accumulation in lamellar bone tissues. The results of this study suggested that different interfacial behaviors cause different types of microdamage accumulation. The ionic interactions between the mineral and collagen phases lead to the formation of linear microcracks, while the van der Waals/viscous shear interactions may facilitate the formation of diffuse damage. In the case of hydrogen/van der Waals bonds, a transitional behavior of microdamage accumulation in bone was observed. The findings of this study may help in understanding the mechanisms of mineral-collagen interactions and its effects on the failure mechanism of bone. PMID:21783104

  20. Estrogen and bone metabolism.

    PubMed

    Väänänen, H K; Härkönen, P L

    1996-05-01

    Estrogen plays an important role in the growth and maturation of bone as well as in the regulation of bone turnover in adult bone. During bone growth estrogen is needed for proper closure of epiphyseal growth plates both in females and in males. Also in young skeleton estrogen deficiency leads to increased osteoclast formation and enhanced bone resorption. In menopause estrogen deficiency induces cancellous as well as cortical bone loss. Highly increased bone resorption in cancellous bone leads to general bone loss and destruction of local architecture because of penetrative resorption and microfractures. In cortical bone the first response of estrogen withdrawal is enhanced endocortical resorption. Later, also intracortical porosity increases. These lead to decreased bone mass, disturbed architecture and reduced bone strength. At cellular level in bone estrogen inhibits differentiation of osteoclasts thus decreasing their number and reducing the amount of active remodeling units. This effect is probably mediated through some cytokines, IL-1 and IL-6 being strongest candidates. Estrogen regulates the expression of IL-6 in bone marrow cells by a so far unknown mechanism. It is still uncertain if the effects of estrogen on osteoblasts is direct or is due to coupling phenomenon between bone formation to resorption. PMID:8865143

  1. Experimental assessment of nutrition and bone growth's velocity effects on Harris lines formation.

    PubMed

    Alfonso-Durruty, Marta P

    2011-06-01

    Harris lines (HL) are radio-opaque transverse lines traditionally associated with stressors that halt or decelerate growth in humans. Harris lines' status as a stress marker is, however, questionable because their association to illness and deficient growth is low and they commonly form in the absence of stress during periods of accelerated growth. To assess Harris line's reliability as a stress marker, this study examined their association with nutritional status and bone growth velocity through an experimental study in rabbits. Forty-five New Zealand White rabbits were divided into: Control (normal laboratory conditions), Experimental-1 (moderately undernourished), and Experimental-2 (periodically fasted) groups during their growth. Variables analyzed included weight, forelimb length, humeral diaphyseal length, diaphyseal growth velocity, and number of Harris lines. Fewer lines were observed by the end of the study among Experimental-1 animals. More Harris lines formed during periods of rapid growth in the absence of nutritional stress. Accordingly, Harris lines are a poor marker of stress. Intrinsic limitations to paleopathological studies can be overcome, but even the most careful attentiveness to multiple stress markers and cultural context will go amiss if the markers used are unreliable. PMID:21469071

  2. Human recombinant cementum attachment protein (hrPTPLa/CAP) promotes hydroxyapatite crystal formation in vitro and bone healing in vivo.

    PubMed

    Montoya, Gonzalo; Arenas, Jesús; Romo, Enrique; Zeichner-David, Margarita; Alvarez, Marco; Narayanan, A Sampath; Velázquez, Ulises; Mercado, Gabriela; Arzate, Higinio

    2014-12-01

    Cementum extracellular matrix is similar to other mineralized tissues; however, this unique tissue contains molecules only present in cementum. A cDNA of these molecules, cementum attachment protein (hrPTPLa/CAP) was cloned and expressed in a prokaryotic system. This molecule is an alternative splicing of protein tyrosine phosphatase-like A (PTPLa). In this study, we wanted to determine the structural and functional characteristics of this protein. Our results indicate that hrPTPLa/CAP contains a 43.2% ?-helix, 8.9% ?-sheet, 2% ?-turn and 45.9% random coil secondary structure. Dynamic light scattering shows that this molecule has a size distribution of 4.8 nm and aggregates as an estimated mass of 137 kDa species. AFM characterization and FE-SEM studies indicate that this protein self-assembles into nanospheres with sizes ranging from 7.0 to 27 nm in diameter. Functional studies demonstrate that hrPTPLa/CAP promotes hydroxyapatite crystal nucleation: EDS analysis revealed that hrPTPLa/CAP-induced crystals had a 1.59 ± 0.06 Ca/P ratio. Further confirmation with MicroRaman spectrometry and TEM confirm the presence of hydroxyapatite. In vivo studies using critical-size defects in rat cranium showed that hrPTPLa/CAP promoted 73% ± 2.19% and 87% ± 1.97% new bone formation at 4 and 8 weeks respectively. Although originally identified in cementum, PTPLa/CAP is very effective at inducing bone repair and healing and therefore this novel molecule has a great potential to be used for mineralized tissue bioengineering and tissue regeneration. PMID:25263524

  3. Zebrafish sp7:EGFP: a transgenic for studying otic vesicle formation, skeletogenesis, and bone regeneration

    PubMed Central

    DeLaurier, April; Eames, B. Frank; Blanco-Sánchez, Bernardo; Peng, Gang; He, Xinjun; Swartz, Mary E.; Ullmann, Bonnie; Westerfield, Monte; Kimmel, Charles B.

    2010-01-01

    Summary We report the expression pattern and construction of a transgenic zebrafish line for a transcription factor involved in otic vesicle formation and skeletogenesis. The zinc finger transcription factor sp7 (formerly called osterix) is reported as a marker of osteoblasts. Using bacterial artificial chromosome (BAC)-mediated transgenesis, we generated a zebrafish transgenic line for studying skeletal development, Tg(sp7:EGFP)b1212. Using a zebrafish BAC, EGFP was introduced downstream of the regulatory regions of sp7 and injected into 1 cell-stage embryos. In this transgenic line, GFP expression reproduces endogenous sp7 gene expression in the otic placode and vesicle, and in forming skeletal structures. GFP-positive cells were also detected in adult fish, and were found associated with regenerating fin rays post-amputation. This line provides an essential tool for the further study of zebrafish otic vesicle formation and the development and regeneration of the skeleton. PMID:20506187

  4. Ambient Fine Particulate Matter Suppresses In Vivo Proliferation of Bone Marrow Stem Cells through Reactive Oxygen Species Formation

    PubMed Central

    Cui, Yuqi; Jia, Fengpeng; He, Jianfeng; Xie, Xiaoyun; Li, Zhihong; Fu, Minghuan; Hao, Hong; Liu, Ying; Liu, Dylan Z.; Cowan, Peter J.; Zhu, Hua; Sun, Qinghua; Liu, Zhenguo

    2015-01-01

    Aims Some environmental insults, such as fine particulate matter (PM) exposure, significantly impair the function of stem cells. However, it is unknown if PM exposure could affect the population of bone marrow stem cells (BMSCs). The present study was to investigate the effects of PM on BMSCs population and related mechanism(s). Main Metheods PM was intranasally distilled into male C57BL/6 mice for one month. Flow cytometry with antibodies for BMSCs, Annexin V and BrdU ware used to determine the number of BMSCs and the levels of their apoptosis and proliferation in vivo. Phosphorylated Akt (P-Akt) level was determined in the BM cells with western blotting. Intracellular reactive oxygen species (ROS) formation was quantified using flow cytometry analysis. To determine the role of PM-induced ROS in BMSCs population, proliferation, and apotosis, experiments were repeated using N-acetylcysteine (NAC)-treated wild type mice or a triple transgenic mouse line with overexpression of antioxidant network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase-1 with decreased in vivo ROS production. Key Findings PM treatment significantly reduced BMSCs population in association with increased ROS formation, decreased P-Akt level, and inhibition of proliferation of BMSCs without induction of apoptosis. NAC treatment or AON overexpression with reduced ROS formation effectively prevented PM-induced reduction of BMSCs population and proliferation with partial recovery of P-Akt level. Significance PM exposure significantly decreased the population of BMSCs due to diminished proliferation via ROS-mediated mechanism (could be partially via inhibition of Akt signaling). PMID:26058063

  5. Crucial vasculoprotective role of the whole nitric oxide synthase system in vascular lesion formation in mice: Involvement of bone marrow-derived cells.

    PubMed

    Furuno, Yumi; Morishita, Tsuyoshi; Toyohira, Yumiko; Yamada, Sohsuke; Ueno, Susumu; Morisada, Naoya; Sugita, Kazunari; Noguchi, Katsuhiko; Sakanashi, Mayuko; Miyata, Hironori; Tanimoto, Akihide; Sasaguri, Yasuyuki; Shimokawa, Hiroaki; Otsuji, Yutaka; Yanagihara, Nobuyuki; Tamura, Masahito; Tsutsui, Masato

    2011-10-30

    Although all three nitric oxide (NO) synthases (nNOS, iNOS, and eNOS) are expressed in injured arteries, it remains to be elucidated the role of the NOSs in their entirety in the vascular lesion formation. We addressed this issue in mice deficient in all NOS genes. Vascular injury was induced by permanent ligation of a unilateral carotid artery in wild-type (WT), singly, and triply NOS(-/-) mice. Two weeks after the procedure, constrictive vascular remodeling and neointimal formation were recognized in the ligated arteries. While constrictive remodeling was noted in the nNOS(-/-) and iNOS(-/-) genotypes, it was most accelerated in the n/i/eNOS(-/-) genotype. While neointimal formation was evident in the eNOS(-/-) and nNOS(-/-) genotypes, it was also most aggravated in the n/i/eNOS(-/-) genotype. Those lesions were reversed by long-term treatment with isosorbide dinitrate, a NO donor. Finally, we examined the involvement of bone marrow-derived cells in the vascular lesion formation. Bone marrow from the WT, singly, or triply NOS(-/-) mice was transplanted into the WT mice, and then the carotid ligation was performed. Intriguingly, constrictive remodeling and neointimal formation were both similarly most exacerbated in the case of the n/i/eNOS(-/-) bone marrow transplantation. These results indicate that the complete disruption of all the NOS genes causes markedly accelerated vascular lesion formation caused by blood flow disruption in mice in vivo, demonstrating the crucial vasculoprotective role of the whole endogenous NOS system. Our findings also suggest that the NOS system in bone marrow-derived cells may be involved in this vasculoprotective mechanism. PMID:21767657

  6. Tilt grain boundary instabilities in three-dimensional lamellar patterns.

    PubMed

    Huang, Zhi-Feng; Viñals, Jorge

    2005-03-01

    We identify a finite wave-number instability of a 90 degrees tilt grain boundary in three-dimensional lamellar phases which is absent in two-dimensional configurations. Both a stability analysis of the slowly varying amplitude or envelope equation for the boundary, and a direct numerical solution of an order parameter model equation are presented. The instability mode involves two-dimensional perturbations of the planar base boundary, and is suppressed for purely one-dimensional perturbations. We find that both the most unstable wave numbers and their growth rate increase with epsilon , the dimensionless distance away from threshold of the lamellar phase. PMID:15903429

  7. Taphonomy and depositional environment of a Lower Cretaceous monospecific dinosaur bone assemblage (Puesto Quiroga Member, Lohan Cura Formation), Neuquén Province, Argentina

    NASA Astrophysics Data System (ADS)

    Garrido, Alberto Carlos; Salgado, Leonardo

    2015-08-01

    The Puesto Díaz Quarry (Lohan Cura Formation, Lower Cretaceous of Neuquén Basin, Argentina) consists of a monospecific dinosaur bone assemblage that includes 126 specimens from, at least, three individuals of the rebbachisaurid sauropod Comahuesaurus windhauseni. The bonebed was originated as a debris flow of an ephemeral-river bed, in distal areas of low relief. Bones are disarticulated, three-dimensionally distributed through the host facies, showing a normal grading arrangement, which can be correlated with the size, shape and hydraulic behavior inferred for each specimen. Taphonomic evidence suggests that the bones did not experience a prolonged transport, and that these were quickly buried by the debris flow event. The fact that there are more than one individual of the same species suggests a mass mortality by a catastrophic event. Scattered skeletal elements would indicate that the corpses must have been subaerially exposed, long enough to allow disarticulation by scavenging, decay, and defleshing.

  8. Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive Gs-G protein signaling in osteoblasts.

    PubMed

    Wattanachanya, Lalita; Wang, Liping; Millard, Susan M; Lu, Wei-Dar; O'Carroll, Dylan; Hsiao, Edward C; Conklin, Bruce R; Nissenson, Robert A

    2015-05-01

    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 Gs-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 Gs 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 Gs G protein-coupled receptor signaling, at the cellular 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 Gs-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of Gs signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to Gs signaling in mature OBs. PMID:25704759

  9. Bone Diseases

    MedlinePLUS

    ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bone disease can make bones easy to break Bones can also develop cancer and infections Other bone diseases are caused by poor nutrition, genetic factors or ...

  10. Carboxyl-modified single-wall carbon nanotubes improve bone tissue formation in vitro and repair in an in vivo rat model

    PubMed Central

    Barrientos-Durán, Antonio; Carpenter, Ellen M; zur Nieden, Nicole I; Malinin, Theodore I; Rodríguez-Manzaneque, Juan Carlos; Zanello, Laura P

    2014-01-01

    The clinical management of bone defects caused by trauma or nonunion fractures remains a challenge in orthopedic practice due to the poor integration and biocompatibility properties of the scaffold or implant material. In the current work, the osteogenic properties of carboxyl-modified single-walled carbon nanotubes (COOH–SWCNTs) were investigated in vivo and in vitro. When human preosteoblasts and murine embryonic stem cells were cultured on coverslips sprayed with COOH–SWCNTs, accelerated osteogenic differentiation was manifested by increased expression of classical bone marker genes and an increase in the secretion of osteocalcin, in addition to prior mineralization of the extracellular matrix. These results predicated COOH–SWCNTs’ use to further promote osteogenic differentiation in vivo. In contrast, both cell lines had difficulties adhering to multi-walled carbon nanotube-based scaffolds, as shown by scanning electron microscopy. While a suspension of SWCNTs caused cytotoxicity in both cell lines at levels >20 ?g/mL, these levels were never achieved by release from sprayed SWCNTs, warranting the approach taken. In vivo, human allografts formed by the combination of demineralized bone matrix or cartilage particles with SWCNTs were implanted into nude rats, and ectopic bone formation was analyzed. Histological analysis of both types of implants showed high permeability and pore connectivity of the carbon nanotube-soaked implants. Numerous vascularization channels appeared in the formed tissue, additional progenitor cells were recruited, and areas of de novo ossification were found 4 weeks post-implantation. Induction of the expression of bone-related genes and the presence of secreted osteopontin protein were also confirmed by quantitative polymerase chain reaction analysis and immunofluorescence, respectively. In summary, these results are in line with prior contributions that highlight the suitability of SWCNTs as scaffolds with high bone-inducing capabilities both in vitro and in vivo, confirming them as alternatives to current bone-repair therapies. PMID:25246785

  11. Targeted inactivation of the murine Abca3 gene leads to respiratory failure in newborns with defective lamellar bodies

    SciTech Connect

    Hammel, Markus; Michel, Geert; Hoefer, Christina; Klaften, Matthias; Mueller-Hoecker, Josef; Angelis, Martin Hrabe de; Holzinger, Andreas . E-mail: andreas.holzinger@med.uni-muenchen.de

    2007-08-10

    Mutations in the human ABCA3 gene, encoding an ABC-transporter, are associated with respiratory failure in newborns and pediatric interstitial lung disease. In order to study disease mechanisms, a transgenic mouse model with a disrupted Abca3 gene was generated by targeting embryonic stem cells. While heterozygous animals developed normally and were fertile, individuals homozygous for the altered allele (Abca3-/-) died within one hour after birth from respiratory failure, ABCA3 protein being undetectable. Abca3-/- newborns showed atelectasis of the lung in comparison to a normal gas content in unaffected or heterozygous littermates. Electron microscopy demonstrated the absence of normal lamellar bodies in type II pneumocytes. Instead, condensed structures with apparent absence of lipid content were found. We conclude that ABCA3 is required for the formation of lamellar bodies and lung surfactant function. The phenotype of respiratory failure immediately after birth corresponds to the clinical course of severe ABCA3 mutations in human newborns.

  12. Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids.

    PubMed

    Li, Y; Seifert, M F; Ney, D M; Grahn, M; Grant, A L; Allen, K G; Watkins, B A

    1999-07-01

    A study was designed to examine the effects of dietary conjugated linoleic acid (CLA) on serum concentrations of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBP) and the relationship of these factors to bone metabolism. Weanling male rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 days. Treatments included 0 g/kg or 10 g/kg of CLA and soybean oil (SBO) or menhaden oil + safflower oil (MSO) following a 2 x 2 factorial design. Serum IGFBP was influenced by dietary polyunsaturated fatty acid (PUFA) type ((n-6) and (n-3)) and CLA (p = 0.01 for 38-43 kDa bands corresponding to IGFBP-3). CLA increased IGFBP level in rats fed SBO (p = 0.05) but reduced it in those fed MSO (p = 0.01). Rats fed MSO had the highest serum IGFBP-3 level. Both (n-3) fatty acids and CLA lowered ex vivo prostaglandin E2 production in bone organ culture. In tibia, rats given CLA had reduced mineral apposition rate (3.69 vs. 2.79 microm/day) and bone formation rate (BFR) (0.96 vs. 0.65 microm3/microm2/day); however, the BFR tended to be higher with MSO. Dietary lipid treatments did not affect serum intact osteocalcin or bone mineral content. These results showed that dietary PUFA type and CLA modulate local factors that regulate bone metabolism. PMID:10404015

  13. Swelling and shrinking kinetics of a lamellar gel phase 

    E-print Network

    Egelhaaf, Stefan U; Baker, M.E.; Shaw, N.; Fairhurst, David John

    2008-05-01

    We investigate the swelling and shrinking of L-beta lamellar gel phases composed of surfactant and fatty alcohol after contact with aqueous poly(ethyleneglycol) solutions. The height change Delta h(t) is diffusionlike with a swelling coefficient S...

  14. Optimal lamellar arrangement in fish gills Keunhwan Parka

    E-print Network

    Kim, Ho-Young

    oxygen has considerably low solubility and diffusivity in water, the efficiency of respiration of lamellae enclosing a capillary blood network, as shown in Fig. 1 (1, 2). Oxygen-rich water passes through oxygen transfer that occurs in fish gills. As water passes through the narrow lamellar channels

  15. Mesoporous Zirconium Phenylenesiliconate-phosphonate Hybrids with Ordered Lamellar Nanostructures.

    PubMed

    Maeda, Kazuyuki; Kobayashi, Hiroki; Oguro, Kaku; Otsu, Masato; Kondo, Atsushi; Maki, Tei

    2015-11-16

    Novel ordered lamellar mesostructure pZrPS-2 was hydrothermally prepared by using zirconium propoxide and 4-(EtO)2 OPC6 H4 Si(OEt)3 (pPPS-E), which was hydrolyzed to organic building units substituted with both siliconate and phosphonate groups, in the presence of Cn TAB and TMAOH. The pZrPS-2 materials were obtained at a Zr/PPS ratio of 2 or higher and the basal spacing was increased by using a longer-chain surfactant (n=12-18). Removal of the occluded surfactants at 300?°C resulted in retention of the lamellar structure with negligible shrinkage of the interlayer distance. Nitrogen adsorption studies revealed the ordered mesoporous nature of pZrPS-2 with a pore diameter of approximately 2 to 3?nm. The lamellar structure is assumed to be composed of layers that include zirconia-based crystalline nanodomains and interlayer pillars mainly based on PPS units. Although lamellar structures with the same crystalline phase also formed when no surfactant was added or when the meta isomer of PPS was used, no mesoporous materials were obtained except pZrPS-2. A possible schematic model to elucidate these results is also proposed. PMID:26427615

  16. [Bone turnover marker].

    PubMed

    Miura, Masakazu; Satoh, Yuki

    2015-10-01

    Recently the clinical application of bone turnover markers (BTMs) have been achieved significant progress and the measurements of these indices give us better understanding of pathogenesis of osteoporosis. BTMs are known the bone formation marker, the bone resorption marker and the bone matrix-related marker, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the influence of renal function on BTMs. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the evaluation of therapeutic effects of bone antiresorption drugs and/or bone formation promoting drug using bone resorption markers and/or bone formation marker were corrected newly in the guideline 2012 edition. Moreover, BTMs were suggested to contribute to adhere with osteoporosis treatment. BTMs are adapted to selection of the drug for osteoporosis and to evaluate the drug efficacy. Therefore, it is very important to guide the proper application and assessment of BTMs in clinical practice. PMID:26529926

  17. Lamellar magnetism in the haematite-ilmenite series as an explanation for strong remanent magnetization.

    PubMed

    Robinson, Peter; Harrison, Richard J; McEnroe, Suzanne A; Hargraves, Robert B

    2002-08-01

    Magnetic anomalies associated with slowly cooled igneous and metamorphic rocks are commonly attributed to the presence of the mineral magnetite. Although the intermediate members of the ilmenite-haematite mineral series can also carry a strong ferrimagnetic remanence, it is preserved only in rapidly cooled volcanic rocks, where formation of intergrowths of weakly magnetic haematite and paramagnetic ilmenite is suppressed. But the occurrence of unusually large and stable magnetic remanence in rocks containing such intergrowths has been known for decades, and has recently been the subject of intense investigation. These unmixed oxide phases have been shown to contain pervasive exsolution lamellae with thickness from 100 microm down to about 1 nm (one unit cell). These rocks, many of which contain only a few per cent of such oxides, show natural remanent magnetizations up to 30 A m(-1) --too strong to be explained even by pure haematite in an unsaturated state. Here we propose a new ferrimagnetic substructure created by ferrous-ferric 'contact layers' that reduce charge imbalance along lamellar contacts between antiferromagnetic haematite and paramagnetic ilmenite. We estimate that such a lamellar magnetic material can have a saturation magnetization up to 55 kA m(-1) --22 times stronger than pure haematite-- while retaining the high coercivity and thermal properties of single-domain haematite. PMID:12152075

  18. Stress response and structural transitions in sheared gyroidal and lamellar amphiphilic mesophases: lattice-Boltzmann simulations

    E-print Network

    Nelido Gonzalez-Segredo; Jens Harting; Giovanni Giupponi; Peter V. Coveney

    2006-01-20

    We report on the stress response of gyroidal and lamellar amphiphilic mesophases to steady shear simulated using a bottom-up lattice-Boltzmann model for amphiphilic fluids and sliding periodic (Lees-Edwards) boundary conditions. We study the gyroid per se (above the sponge-gyroid transition, of high crystallinity) and the molten gyroid (within such a transition, of shorter-range order). We find that both mesophases exhibit shear-thinning, more pronounced and at lower strain rates for the molten gyroid. At late times after the onset of shear, the skeleton of the crystalline gyroid becomes a structure of interconnected irregular tubes and toroidal rings, mostly oriented along the velocity ramp imposed by the shear, in contradistinction with free-energy Langevin-diffusion studies which yield a much simpler structure of disentangled tubes. We also compare the shear stress and deformation of lamellar mesophases with and without amphiphile when subjected to the same shear flow applied normal to the lamellae. We find that the presence of amphiphile allows (a) the shear stress at late times to be higher than in the case without amphiphile, and (b) the formation of rich patterns on the sheared interface, characterised by alternating regions of high and low curvature.

  19. Novel porous Al2O3-SiO2-TiO2 bone grafting materials: formation and characterization.

    PubMed

    Naga, Salma M; El-Kady, Abeer M; El-Maghraby, Hesham F; Awaad, Mohamed; Detsch, Rainer; Boccaccini, Aldo R

    2014-02-01

    The present article deals with the development of 3D porous scaffolds for bone grafting. They were prepared based on rapid fluid infiltration of Al2O3-SiO2 sol into a polyethylene non-woven fabric template structure. Titanium dioxide in concentration equal to 5 wt% was added to the Al2O3-SiO2 mixture to produce Al2O3-SiO2-TiO2 composite scaffolds. The prepared scaffolds are characterized by means of X-ray diffraction, scanning electron microscopy and three-point bending test techniques. The bioactivity of the produced bodies is discussed, including the in vitro and in vivo assessments. The produced scaffolds exhibit mean total porosity of 66.0% and three-point bending strength of 7.1?MPa. In vitro studies showed that MG-63 osteoblast-like cells attach and spread on the scaffolds surfaces. Furthermore, cells grew through the scaffolds and start to produce extra-cellular matrix. Additionally, in vivo studies revealed the ability of the porous scaffolds to regenerate bone tissue in femur defects of albino rats 5 months post surgery. Histological analysis showed that the defect is almost entirely filled with new bone. The formed bone is characterized as a mature bone. The produced bone grafts are intended to be used as bone substitute or bone filler as their degradation products caused no inflammatory effects. PMID:23594680

  20. Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model.

    PubMed

    Córdova, L A; Trichet, V; Escriou, V; Rosset, P; Amiaud, J; Battaglia, S; Charrier, C; Berreur, M; Brion, R; Gouin, F; Layrolle, P; Passuti, N; Heymann, D

    2015-02-01

    Receptor activator of nuclear factor kappa-B (RANK) and RANK-ligand are relevant targets for the treatment of polyethylene particle-induced osteolysis. This study assessed the local administration of siRNA, targeting both human RANK and mouse Rank transcripts in a mouse model. Four groups of mice were implanted with polyethylene (PE) particles in the calvaria and treated locally with 2.5, 5 and 10 ?g of RANK siRNA or a control siRNA delivered by the cationic liposome DMAPAP/DOPE. The tissues were harvested at day 9 after surgery and evaluated by micro-computed tomography, tartrate-resistant acid phosphatase (TRAP) immunohistochemistry for macrophages and osteoblasts, and gene relative expression of inflammatory and osteolytic markers. 10 ?g of RANK siRNA exerted a protective effect against PE particle-induced osteolysis, decreasing the bone loss and the osteoclastogenesis, demonstrated by the significant increase in the bone volume (P<0.001) and by the reduction in both the number of TRAP(+) cells and osteoclast activity (P<0.01). A bone anabolic effect demonstrated by the formation of new trabecular bone was confirmed by the increased immunopositive staining for osteoblast-specific proteins. In addition, 5 and 10 ?g of RANK siRNA downregulated the expression of pro-inflammatory cytokines (P<0.01) without depletion of macrophages. Our findings show that RANK siRNA delivered locally by a synthetic vector may be an effective approach for reducing osteolysis and may even stimulate bone formation in aseptic loosening of prosthetic implants. PMID:25462844

  1. 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 13weeks 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. PMID:26485046

  2. Controlled release of simvastatin from in situ forming hydrogel triggers bone formation in MC3T3-E1 cells.

    PubMed

    Park, Yoon Shin; David, Allan E; Park, Kyung Min; Lin, Chia-Ying; Than, Khoi D; Lee, Kyuri; Park, Jun Beom; Jo, Inho; Park, Ki Dong; Yang, Victor C

    2013-04-01

    Simvastatin (SIM), a drug commonly administered for the treatment of hypercholesterolemia, has been recently reported to induce bone regeneration/formation. In this study, we investigated the properties of hydrogel composed of gelatin-poly(ethylene glycol)-tyramine (GPT) as an efficient SIM delivery vehicle that can trigger osteogenic differentiation. Sustained delivery of SIM was achieved through its encapsulation in an injectable, biodegradable GPT-hydrogel. Cross-linking of the gelatin-based GPT-hydrogel was induced by the reaction of horse radish peroxidase and H(2)O(2). GPT-hydrogels of three different matrix stiffness, 1,800 (GPT-hydrogel1), 5,800 (GPT-hydrogel2), and 8,400 Pa (GPT-hydrogel3) were used. The gelation/degradation time and SIM release profiles of hydrogels loaded with two different concentrations of SIM, 1 and 3 mg/ml, were also evaluated. Maximum swelling times of GPT-hydrogel1, GPT-hydrogel2, and GPT-hydrogel3 were observed to be 6, 12, and 20 days, respectively. All GPT-hydrogels showed complete degradation within 55 days. The in vitro SIM release profiles, investigated in PBS buffer (pH 7.4) at 37°C, exhibited typical biphasic release patterns with the initial burst being more rapid with GPT-hydrogel1 compared with GPT-hydrogel3. Substantial increase in matrix metalloproteinase-13, osteocalcin expression levels, and mineralization were seen in osteogenic differentiation system using MC3T3-E1 cells cultured with GPT-hydrogels loaded with SIM in a dose-dependent manner. This study demonstrated that controlled release of SIM from a biodegradable, injectable GPT-hydrogel had a promising role for long-term treatment of chronic degenerative diseases such as disc degenerative disease. PMID:23250670

  3. The ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation.

    PubMed

    Ono, Koichiro; Karolak, Matthew R; Ndong, Jean de la Croix; Wang, Weixi; Yang, Xiangli; Elefteriou, Florent

    2013-08-01

    The severe defects in growth plate development caused by chondrocyte extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) gain or loss-of-function suggest that tight spatial and temporal regulation of mitogen-activated protein kinase signaling is necessary to achieve harmonious growth plate elongation and structure. We provide here evidence that neurofibromin, via its Ras guanosine triphosphatase -activating activity, controls ERK1/2-dependent fibroblast growth factor receptor (FGFR) signaling in chondrocytes. We show first that neurofibromin is expressed in FGFR-positive prehypertrophic and hypertrophic chondrocytes during growth plate endochondral ossification. Using mice lacking neurofibromin 1 (Nf1) in type II collagen-expressing cells, (Nf1col2(-/-) mutant mice), we then show that lack of neurofibromin in post-mitotic chondrocytes triggers a number of phenotypes reminiscent of the ones observed in mice characterized by FGFR gain-of-function mutations. Those include dwarfism, constitutive ERK1/2 activation, strongly reduced Ihh expression and decreased chondrocyte proliferation and maturation, increased chondrocytic expression of Rankl, matrix metalloproteinase 9 (Mmp9) and Mmp13 and enhanced growth plate osteoclastogenesis, as well as increased sensitivity to caspase-9 mediated apoptosis. Using wildtype (WT) and Nf1(-/-) chondrocyte cultures in vitro, we show that FGF2 pulse-stimulation triggers rapid ERK1/2 phosphorylation in both genotypes, but that return to the basal level is delayed in Nf1(-/-) chondrocytes. Importantly, in vivo ERK1/2 inhibition by daily injection of a recombinant form of C-type natriuretic peptide to post-natal pups for 18 days was able to correct the short stature of Nf1col2(-/-) mice. Together, these results underscore the requirement of neurofibromin and ERK1/2 for normal endochondral bone formation and support the notion that neurofibromin, by restraining RAS-ERK1/2 signaling, is a negative regulator of FGFR signaling in differentiating chondrocytes. PMID:23571107

  4. The Ras-GTPase activity of neurofibromin restrains ERK-dependent FGFR signaling during endochondral bone formation

    PubMed Central

    Ono, Koichiro; Karolak, Matthew R.; Ndong, Jean de la Croix; Wang, Weixi; Yang, Xiangli; Elefteriou, Florent

    2013-01-01

    The severe defects in growth plate development caused by chondrocyte extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) gain or loss-of-function suggest that tight spatial and temporal regulation of mitogen-activated protein kinase signaling is necessary to achieve harmonious growth plate elongation and structure. We provide here evidence that neurofibromin, via its Ras guanosine triphosphatase -activating activity, controls ERK1/2-dependent fibroblast growth factor receptor (FGFR) signaling in chondrocytes. We show first that neurofibromin is expressed in FGFR-positive prehypertrophic and hypertrophic chondrocytes during growth plate endochondral ossification. Using mice lacking neurofibromin 1 (Nf1) in type II collagen-expressing cells, (Nf1col2?/? mutant mice), we then show that lack of neurofibromin in post-mitotic chondrocytes triggers a number of phenotypes reminiscent of the ones observed in mice characterized by FGFR gain-of-function mutations. Those include dwarfism, constitutive ERK1/2 activation, strongly reduced Ihh expression and decreased chondrocyte proliferation and maturation, increased chondrocytic expression of Rankl, matrix metalloproteinase 9 (Mmp9) and Mmp13 and enhanced growth plate osteoclastogenesis, as well as increased sensitivity to caspase-9 mediated apoptosis. Using wildtype (WT) and Nf1?/? chondrocyte cultures in vitro, we show that FGF2 pulse-stimulation triggers rapid ERK1/2 phosphorylation in both genotypes, but that return to the basal level is delayed in Nf1?/? chondrocytes. Importantly, in vivo ERK1/2 inhibition by daily injection of a recombinant form of C-type natriuretic peptide to post-natal pups for 18 days was able to correct the short stature of Nf1col2?/? mice. Together, these results underscore the requirement of neurofibromin and ERK1/2 for normal endochondral bone formation and support the notion that neurofibromin, by restraining RAS-ERK1/2 signaling, is a negative regulator of FGFR signaling in differentiating chondrocytes. PMID:23571107

  5. Cholesterol expels ibuprofen from the hydrophobic membrane core and stabilizes lamellar phases in lipid membranes containing ibuprofen.

    PubMed

    Alsop, Richard J; Armstrong, Clare L; Maqbool, Amna; Toppozini, Laura; Dies, Hannah; Rheinstädter, Maikel C

    2015-06-28

    There is increasing evidence that common drugs, such as aspirin and ibuprofen, interact with lipid membranes. Ibuprofen is one of the most common over the counter drugs in the world, and is used for relief of pain and fever. It interacts with the cyclooxygenase pathway leading to inhibition of prostaglandin synthesis. From X-ray diffraction of highly oriented model membranes containing between 0 and 20 mol% ibuprofen, 20 mol% cholesterol, and dimyristoylphosphatidylcholine (DMPC), we present evidence for a non-specific interaction between ibuprofen and cholesterol in lipid bilayers. At a low ibuprofen concentrations of 2 mol%, three different populations of ibuprofen molecules were found: two in the lipid head group region and one in the hydrophobic membrane core. At higher ibuprofen concentrations of 10 and 20 mol%, the lamellar bilayer structure is disrupted and a lamellar to cubic phase transition was observed. In the presence of 20 mol% cholesterol, ibuprofen (at 5 mol%) was found to be expelled from the membrane core and reside solely in the head group region of the bilayers. 20 mol% cholesterol was found to stabilize lamellar membrane structure and the formation of a cubic phase at 10 and 20 mol% ibuprofen was suppressed. The results demonstrate that ibuprofen interacts with lipid membranes and that the interaction is strongly dependent on the presence of cholesterol. PMID:25915907

  6. Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-?B activation and titanium particle-induced osteolysis in a mouse model.

    PubMed

    Huang, Jianbin; Zhou, Lin; Wu, Huafei; Pavlos, Nathan; Chim, Shek Man; Liu, Qian; Zhao, Jinmin; Xue, Wei; Tan, Ren Xiang; Ye, Jiming; Xu, Jun; Ang, Estabelle S; Feng, Haotian; Tickner, Jennifer; Xu, Jiake; Ding, Yue

    2015-01-01

    The RANKL-induced NF-?B signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-?B activation using a luciferase reporter gene assay in RAW264.7 cells, we identified triptolide (PG490), as a candidate compound targeting osteoclast differentiation and osteoclast-mediated osteolysis. Triptolide (PG490) is an active compound of the medicinal herb Tripterygium wilfordii Hook F (TWHF) or Lei Gong Teng with known anti-inflammatory properties. We found that triptolide inhibited osteoclastogenesis and bone resorption, as well as RANKL-induced NF-?B activities as monitored by luciferase reporter gene assays and the nuclear translocation of p65. In vivo studies showed that triptolide attenuates titanium-induced osteolysis and osteoclast formation in a mouse calvarial model. Considering that drugs which protect against localized bone loss are critically needed for the effective treatment of particle-induced osteolysis, our data suggest that triptolide might have therapeutic potential for the treatment of bone lytic diseases caused by prosthetic wear particles. PMID:25448849

  7. Morphogenesis of the compartmentalizing bone around the molar primordia in the mouse mandible during dental developmental stages between lamina, bell-stage, and root formation (E13-P20).

    PubMed

    Radlanski, Ralf J; Renz, Herbert; Zimmermann, Camilla A; Mey, Robert; Matalova, Eva

    2015-07-01

    Despite increasing knowledge of the basic molecular aspects of bone formation and its regulation, the mechanisms of bone morphogenesis leading to a topologically specific shape remain unknown. The formation of the alveolar bone, which houses the dental primordia and later, the dental roots, may serve as a model to understand the formation of bone form in general. Thirty-eight heads of mice (C57 Bl/6J) ranging from stages E13-P20 were used to prepare histological serial sections. For each stage, virtual 3D-reconstructions were made in order to study the morphogenesis of the mandibular molar primordia concomitantly with their surrounding bone. Special focus was given to recording the remodeling pattern. It has been shown that, in early stages (E13, E14), bone formation is characterized by apposition only. In stage E15, the bony crypt around the dental primordia is remodeled mostly by resorption of bone. In stage E18, the bone remodeling pattern shows resorption all along the bony gutter, which houses the molar primordia. The medial and lateral margins are characterized by apposition. At birth (stage P0), a bony septum has begun to form between the primordium m1 and of m2, arising from both sides and characterized by pure apposition of bone. In stage P4, the crypts of m1 and m2, and also that of m3, show bone resorption inside, while the medial and lateral bony margins show apposition of bone throughout. Generally, during development, the bone gradually encapsulates the dental primordia, in such a way that the bone reaches over the dental primordia and leaves only a continuous longish opening of about 200?m width. The opening at the occlusal surface of m1, at the time of eruption, starting at stage P14, appears to have increased in size again. The distance between bone and dental primordium undergoes change during development. In erupted molars, it is around 100?m, during early developmental stages, it may be as less as 20?m. These data show the inevitability of bone remodeling. PMID:25723515

  8. [Pharmacology of bone anabolic agents].

    PubMed

    Matsumoto, Toshio

    2015-10-01

    Bone is constantly remodeled to maintain its volume, structural integrity and strength Currently available bone anabolic agent is teriparatide. Teriparatide increases bone mass and strength via both remodeling-dependent and -independent mechanisms, although remodeling-dependent mechanism overweighs the other. Canonical Wnt signal plays an important role in enhancing osteoblast differentiation and bone formation, and its osteocyte-derived inhibitor, sclerostin, regulates bone formation via the regulation of Wnt signaling. Anti-sclerostin antibody stimulates Wnt signaling and enhances bone formation. Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment. The new modality of anabolic agents via remodeling-independent stimulation of bone formation may open up a new avenue for the treatment of osteoporosis. PMID:26529924

  9. Why GPCRs behave differently in cubic and lamellar lipidic mesophases

    PubMed Central

    2012-01-01

    Recent successes in the crystallographic determination of structures of transmembrane proteins in the G protein-coupled receptor (GPCR) family have established the lipidic cubic phase (LCP) environment as the medium of choice for growing structure-grade crystals by the method termed “in meso”. The understanding of in meso crystallogenesis is currently at a descriptive level. To enable an eventual quantitative, energy-based description of the nucleation and crystallization mechanism, we have examined the properties of the lipidic cubic phase system and the dynamics of the GPCR rhodopsin reconstituted into the LCP with coarse-grained molecular dynamics simulations with the Martini force-field. Quantifying the differences in the hydrophobic/hydrophilic exposure of the GPCR to lipids in the cubic and lamellar phases, we found that the highly curved geometry of the cubic phase provides more efficient shielding of the protein from unfavorable hydrophobic exposure, which leads to a lesser hydrophobic mismatch and less unfavorable hydrophobic–hydrophilic interactions between the protein and lipid–water interface in the LCP, compared to the lamellar phase. Since hydrophobic mismatch is considered a driving force for oligomerization, the differences in exposure mismatch energies between the LCP and the lamellar structures suggest that the latter provide a more favorable setting in which GPCRs can oligomerize as a prelude to nucleation and crystal growth. These new findings lay the foundation for future investigations of in meso crystallization mechanisms related to the transition from the LCP to the lamellar phase and studies aimed at an improved rational approach for generating structure-quality crystals of membrane proteins. PMID:22931253

  10. [Bone architecture and strength on unloading].

    PubMed

    Endo, Itsuro; Matsumoto, Toshio

    2013-07-01

    The bone loss due to space flight or prolonged bed rest observes early stage of unloading and causes both decreased bone formation and increased bone resorption. Mechanical unloading induced not only both tarbecular and cortical bone loss but also greater decline bone structure in weight-bearing bone. These findings and further examination concern about pathophysiolosy will allow for better understanding of unloading-associated bone loss and for development of effective countermeasures. PMID:23811590

  11. Air assisted lamellar keratectomy for the corneal haze model

    PubMed Central

    Kim, Soohyun; Park, Young Woo; Lee, Euiri; Park, Sang Wan; Park, Sungwon; Kim, Jong Whi; Seong, Je Kyung

    2015-01-01

    To standardize the corneal haze model in the resection depth and size for efficient corneal haze development, air assisted lamellar keratectomy was performed. The ex vivo porcine corneas were categorized into four groups depending on the trephined depth: 250 µm (G1), 375 µm (G2), 500 µm (G3) and 750 µm (G4). The stroma was equally ablated at the five measurement sites in all groups. Significant differences were observed between the trephined corneal depths for resection and ablated corneal thickness in G1 (p < 0.001). No significant differences were observed between the trephined corneal depth for resection and the ablated corneal thickness in G2, G3, and G4. The resection percentage was similar in all groups after microscopic imaging of corneal sections. Air assisted lamellar keratectomy (AK) and conventional keratectomy (CK) method were applied to six beagles, after which development of corneal haze was evaluated weekly until postoperative day 28. The occurrence of corneal haze in the AK group was significantly higher than that in the CK group beginning 14 days after surgery. Alpha-smooth muscle actin expression was significantly higher in the AK group (p < 0.001) than the CK group. Air assisted lamellar keratectomy was used to achieve the desired corneal thickness after resection and produce sufficient corneal haze. PMID:25797296

  12. Lamellar Gels and Spontaneous Vesicles in Catanionic Surfactant Mixtures

    SciTech Connect

    Coldren,B.; Warriner, H.; van Zanten, R.; Zasadzinski, J.

    2006-01-01

    Caill{acute e} analysis of the small-angle X-ray line shape of the lamellar phase of 7:3 wt/wt cetyltrimethylammonium tosylate (CTAT)/sodium dodecylbenzene sulfonate (SDBS) bilayers shows that the bending elastic constant is {kappa}= (0.62 {+-} 0.09)kBT. From this and previous results, the Gaussian curvature constant is {kappa}= (-0.9 {+-} 0.2)kBT. For 13:7 wt/wt CTAT/SDBS bilayers, the measured bending elasticity decreases with increasing water dilution, in good agreement with predictions based on renormalization theory, giving {kappa}{sub 0} = 0.28k{sub B}T. These results show that surfactant mixing is sufficient to make {kappa} {approx} k{sub B}T, which promotes strong, Helfrich-type repulsion between bilayers that can dominate the van der Waals attraction. These are necessary conditions for spontaneous vesicles to be equilibrium structures. The measurements of the bending elasticity are confirmed by the transition of the lamellar phase of CTAT/SDBS from a turbid, viscoelastic gel to a translucent fluid as the water fraction is decreased below 40 wt %. Freeze-fracture electron microscopy shows that the gel is characterized by spherulite defects made possible by spontaneous bilayer curvature and low bending elasticity. This lamellar gel phase is common to a number of catanionic surfactant mixtures, suggesting that low bending elasticity and spontaneous curvature are typical of these mixtures that form spontaneous vesicles.

  13. Air assisted lamellar keratectomy for the corneal haze model.

    PubMed

    Kim, Soohyun; Park, Young Woo; Lee, Euiri; Park, Sang Wan; Park, Sungwon; Kim, Jong Whi; Seong, Je Kyung; Seo, Kangmoon

    2015-09-01

    To standardize the corneal haze model in the resection depth and size for efficient corneal haze development, air assisted lamellar keratectomy was performed. The ex vivo porcine corneas were categorized into four groups depending on the trephined depth: 250 µm (G1), 375 µm (G2), 500 µm(G3) and 750 µm (G4). The stroma was equally ablated at the five measurement sites in all groups. Significant differences were observed between the trephined corneal depths for resection and ablated corneal thickness in G1 (p < 0.001). No significant differences were observed between the trephined corneal depth for resection and the ablated corneal thickness in G2, G3, and G4. The resection percentage was similar in all groups after microscopic imaging of corneal sections. Air assisted lamellar keratectomy (AK) and conventional keratectomy (CK) method were applied to six beagles, after which development of corneal haze was evaluated weekly until postoperative day 28. The occurrence of corneal haze in the AK group was significantly higher than that in the CK group beginning 14 days after surgery. Alpha-smooth muscle actin expression was significantly higher in the AK group (p < 0.001) than the CK group. Air assisted lamellar keratectomy was used to achieve the desired corneal thickness after resection and produce sufficient corneal haze. PMID:25797296

  14. Surface modification of nano-silica on the ligament advanced reinforcement system for accelerated bone formation: primary human osteoblasts testing in vitro and animal testing in vivo

    NASA Astrophysics Data System (ADS)

    Li, Mengmeng; Wang, Shiwen; Jiang, Jia; Sun, Jiashu; Li, Yuzhuo; Huang, Deyong; Long, Yun-Ze; Zheng, Wenfu; Chen, Shiyi; Jiang, Xingyu

    2015-04-01

    The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction.The Ligament Advanced Reinforcement System (LARS) has been considered as a promising graft for ligament reconstruction. To improve its biocompatibility and effectiveness on new bone formation, we modified the surface of a polyethylene terephthalate (PET) ligament with nanoscale silica using atom transfer radical polymerization (ATRP) and silica polymerization. The modified ligament is tested by both in vitro and in vivo experiments. Human osteoblast testing in vitro exhibits an ~21% higher value in cell viability for silica-modified grafts compared with original grafts. Animal testing in vivo shows that there is new formed bone in the case of a nanoscale silica-coated ligament. These results demonstrate that our approach for nanoscale silica surface modification on LARS could be potentially applied for ligament reconstruction. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr01439e

  15. Fragmentation of {alpha}{sub 2} plates in a fully lamellar TiAl during creep

    SciTech Connect

    Wang, J.G.; Hsiung, L.M.; Nieh, T.G.

    1999-07-01

    The fragmentation and spheroidization of {alpha}{sub 2} laths in a fully-lamellar TiAl alloy during creep were examined. Three possible mechanisms, Rayleigh's perturbation model, subgrain boundary groove mechanism and intersection of deformation twins with {alpha}{sub 2} lamellae were presented and discussed. During creep deformation, the pile-up of interfacial dislocations leads to a change of planar interface, which, in turn, causes a difference in local chemical potential, and further results in the spheroidization of {alpha}{sub 2} lamellae. On the other hand, the deformation of the {alpha}{sub 2} phase is expected to be induced by the high local stress concentration introduced by the pile up of interfacial dislocations. The dynamic recovery process may lead to the formation of subgrain boundaries in the {alpha}{sub 2} lamellae, which results in the spheroidization and termination of {alpha}{sub 2} lamellae with the aid of diffusion during creep.

  16. Design and application of chitosan/biphasic calcium phosphate porous scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Sendemir-Urkmez, Aylin

    For the restoration of maxillofacial bone tissue, design of novel tissue engineering scaffolds capable of inducing bone remodeling through the delivery of mesenchymal stem cells (MSCs) and an angiogenic growth factor, directly at the site of the defect was investigated in order to replace autogenous cancellous bone grafts with synthetic materials. Porous, three dimensional scaffolds were fabricated by a freeze drying method. In culture media, biphasic calcium phosphate particles within chitosan produced a surface reprecipitate of a composition similar to natural apatite that led to a uniform distribution of cells and mineralized ECM through chemotaxis. Further, the reprecipitation regulated the differentiation pathway and phenotype commitment of stem cells by altering the initial cell attachment morphology and actin cytoskeleton organization. In order to induce neovascularization after implantation, constructs were designed to be loaded with gelatin microspheres that delivered basic fibroblast growth factor (bFGF), a potent angiogenic factor. In vitro proliferation tests performed on fibroblastic cells showed no detectible loss of bFGF activity when delivered through enzymatic degradation of gelatin. Laser scanning confocal microscopy was used to demonstrate that gelatin microspheres can be injected evenly into cell-scaffold constructs owing to the spongy characteristics of the scaffold. To examine the binding interactions of bFGF with surface bound gelatin, a label free biosensor system, Biomolecular INteraction Detection sensor (BIND) was used. Results confirm that the principal interaction that takes place between bFGF and gelatin is electrostatic. Cell loaded tissue engineered constructs were produced in vitro at clinically relevant sizes and implanted with and without bFGF into a porcine mandibular defect model. Tissue engineered constructs facilitated the healing of mandibular defects only if combined with delivery of bFGF via gelatin microspheres. bFGF release from the constructs improved neovascularization in the defect area and subsequently enhanced new bone formation. Although the rate and extent of bone formation was similar in bFGF group to those in empty defects for the period of the study, existence of woven bone in bFGF group suggests that bone formation is continuing while the lamellar structure in empty defects indicates that bone formation in that group was finalized.

  17. Histopathological features of bone regeneration in a canine segmental ulnar defect model

    PubMed Central

    2014-01-01

    Background Today, finding an ideal biomaterial to treat the large bone defects, delayed unions and non-unions remains a challenge for orthopaedic surgeions and researchers. Several studies have been carried out on the subject of bone regeneration, each having its own advantages. The present study has been designed in vivo to evaluate the effects of cellular auto-transplantation of tail vertebrae on healing of experimental critical bone defect in a dog model. Methods Six indigenous breeds of dog with 32?±?3.6 kg average weight from both sexes (5 males and 1 female) received bilateral critical-sized ulnar segmental defects. After determining the health condition, divided to 2 groups: The Group I were kept as control I (n?=?1) while in Group II (experimental group; n?=?5) bioactive bone implants were inserted. The defects were implanted with either autogeneic coccygeal bone grafts in dogs with 3-4 cm diaphyseal defects in the ulna. Defects were stabilized with internal plate fixation, and the control defects were not stabilized. Animals were euthanized at 16 weeks and analyzed by histopathology. Results Histological evaluation of this new bone at sixteen weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. And also reformation cortical compartment and reconstitution of marrow space were observed at the graft-host interface together with graft resorption and necrosis responses. Finally, our data were consistent with the osteoconducting function of the tail autograft. Conclusions Our results suggested that the tail vertebrae autograft seemed to be a new source of autogenous cortical bone in order to supporting segmental long bone defects in dogs. Furthermore, cellular autotransplantation was found to be a successful replacement for the tail vertebrae allograft bone at 3-4 cm segmental defects in the canine mid- ulna. Clinical application using graft expanders or bone autotransplantation should be used carefully and requires further investigation. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2028232688119271. PMID:24636669

  18. Low-Level Vibrations Retain Bone Marrow's Osteogenic Potential and Augment Recovery of Trabecular Bone

    E-print Network

    Low-Level Vibrations Retain Bone Marrow's Osteogenic Potential and Augment Recovery of Trabecular Mechanical disuse will bias bone marrow stromal cells towards adipogenesis, ultimately compromising% greater marrow osteoprogenitor population, 83% greater osteoblast surfaces, 59% greater bone formation

  19. Altered bone turnover during spaceflight

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Morey, E. R.; Liu, C.; Baylink, D. J.

    1982-01-01

    Modifications in calcium metabolism during spaceflight were studied, using parameters that reflect bone turnover. Bone formation rate, medullary area, bone length, bone density, pore size distribution, and differential bone cell number were evaluated in growing rate both immediately after and 25 days after orbital spaceflights aboard the Soviet biological satellites Cosmos 782 and 936. The primary effect of space flight on bone turnover was a reversible inhibition of bone formation at the periosteal surface. A simultaneous increase in the length of the periosteal arrest line suggests that bone formation ceased along corresponding portions of that surface. Possible reasons include increased secretion of glucocorticoids and mechanical unloading of the skeleton due to near-weightlessness, while starvation and immobilization are excluded as causes.

  20. Nanomaterials and bone regeneration

    PubMed Central

    Gong, Tao; Xie, Jing; Liao, Jinfeng; Zhang, Tao; Lin, Shiyu; Lin, Yunfeng

    2015-01-01

    The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic (mainly collagen) and inorganic (mainly nano-hydroxyapatite) components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part. PMID:26558141

  1. Normal Bone Anatomy and Physiology

    PubMed Central

    Clarke, Bart

    2008-01-01

    This review describes normal bone anatomy and physiology as an introduction to the subsequent articles in this section that discuss clinical applications of iliac crest bone biopsy. The normal anatomy and functions of the skeleton are reviewed first, followed by a general description of the processes of bone modeling and remodeling. The bone remodeling process regulates the gain and loss of bone mineral density in the adult skeleton and directly influences bone strength. Thorough understanding of the bone remodeling process is critical to appreciation of the value of and interpretation of the results of iliac crest bone histomorphometry. Osteoclast recruitment, activation, and bone resorption is discussed in some detail, followed by a review of osteoblast recruitment and the process of new bone formation. Next, the collagenous and noncollagenous protein components and function of bone extracellular matrix are summarized, followed by a description of the process of mineralization of newly formed bone matrix. The actions of biomechanical forces on bone are sensed by the osteocyte syncytium within bone via the canalicular network and intercellular gap junctions. Finally, concepts regarding bone remodeling, osteoclast and osteoblast function, extracellular matrix, matrix mineralization, and osteocyte function are synthesized in a summary of the currently understood functional determinants of bone strength. This information lays the groundwork for understanding the utility and clinical applications of iliac crest bone biopsy. PMID:18988698

  2. Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging.

    PubMed

    Gao, Guifang; Yonezawa, Tomo; Hubbell, Karen; Dai, Guohao; Cui, Xiaofeng

    2015-10-01

    Inkjet bioprinting is one of the most promising additive manufacturing approaches for tissue fabrication with the advantages of high speed, high resolution, and low cost. The limitation of this technology is the potential damage to the printed cells and frequent clogging of the printhead. Here we developed acrylated peptides and co-printed with acrylated poly(ethylene glycol) (PEG) hydrogel with simultaneous photopolymerization. At the same time, the bone marrow-derived human mesenchymal stem cells (hMSCs) were precisely printed during the scaffold fabrication process so the cells were delivered simultaneously with minimal UV exposure. The multiple steps of scaffold synthesis and cell encapsulation were successfully combined into one single step using bioprinting. The resulted peptide-conjugated PEG scaffold demonstrated excellent biocompatibility, with a cell viability of 87.9 ± 5.3%. Nozzle clogging was minimized due to the low viscosity of the PEG polymer. With osteogenic and chondrogenic differentiation, the bioprinted bone and cartilage tissue demonstrated excellent mineral and cartilage matrix deposition, as well as significantly increased mechanical properties. Strikingly, the bioprinted PEG-peptide scaffold dramatically inhibited hMSC hypertrophy during chondrogenic differentiation. Collectively, bioprinted PEG-peptide scaffold and hMSCs significantly enhanced osteogenic and chondrogenic differentiation for robust bone and cartilage formation with minimal printhead clogging. PMID:25641582

  3. Lamellar to tubular conformational changes in the endoplasmic reticulum of the retinal pigment epithelium of the newt, Notophthalmus viridescens.

    PubMed

    Yorke, M A; Dickson, D H

    1985-01-01

    The retinal pigment epithelium (RPE) of the newt (Notophthalmus viridescens) was examined ultrastructurally under both in-vivo and in-vitro conditions. Five distinct conformations of smooth endoplasmic reticulum (SER), two lamellar and three tubular, were observed. The two lamellar conformations included myeloid bodies, which have previously been described (Yorke and Dickson 1984), and fenestrated SER. The latter appeared as layers of flattened or curved cisternae which were penetrated by fenestrations. Fenestrated SER became indistinguishable from the highly branched and convoluted random-tubular SER through the formation of an intermediate configuration ("tubular sheets"). The remaining tubular SER conformations appeared to arise from random-tubular SER through a progressive reduction in branching and a straightening of individual tubules. Fascicular SER was represented by the hexagonal organization of straight, unbranched tubules into bundles (fascicles). Spiral SER consisted of a similar hexagonal arrangement, but the unbranched tubules spiralled about one another. Neighbouring tubules in areas of spiral SER were also joined together by pairs of electron-dense bars. Although lamellar (especially myeloid bodies) and random-tubular configurations of the SER were common features in vivo, fascicular and spiral SER were primarily conformations encountered in vitro. Conditions favouring bilayer lipid phases also appear to facilitate the formation of both myeloid bodies and fascicular SER. These conditions included increased duration of incubation, low (less than 20 degrees C) incubation temperatures, and Ca2+-free incubations with EGTA. Random-tubular SEB was most prevalent in media supplemented with fetal calf serum and also after warmer (30 degrees C) incubation temperatures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4028144

  4. Bone Loss in IBD

    MedlinePLUS

    ... formation occurred at exactly the same pace, bone mass would remain the same. But that isn’t ... experts, increasing age, female gender, and low body mass index (BMI) put people with IBD at greater ...

  5. Analyzing the behavior of a porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite for healing of bone defects.

    PubMed

    Xiong, Yan; Ren, Cheng; Zhang, Bin; Yang, Hongsheng; Lang, Yun; Min, Li; Zhang, Wenli; Pei, Fuxing; Yan, Yonggang; Li, Hong; Mo, Anchun; Tu, Chongqi; Duan, Hong

    2014-01-01

    The aim of this study was to analyze the behavior of the porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite grafted for bone defect repair through a series of biological safety experiments, animal experiments, and a more than 5-year long clinical follow-up. The biological safety experiments, carried out in accordance with the Chinese Guo Biao and Tolerancing (GB/T)16886 and GB/T16175, revealed that porous n-HA/PA66 composite had no cytotoxicity, no sensitization effect, no pyrogenic reaction, and that its hemolysis rate was 0.59% (less than 5%). Rabbit models of tibia defects with grafted porous n-HA/PA66 composite were established. After 2 weeks, the experiment showed that osteogenesis was detected in the porous n-HA/PA66 composite; the density of new bone formation was similar to the surrounding host bone at 12 weeks. After 26 weeks, the artificial bone rebuilt to lamellar bone completely. In the clinical study, a retrospective review was carried out for 21 patients who underwent serial radiographic assessment after treatment with porous n-HA/PA66 composite grafts following bone tumor resection. All wounds healed to grade A. No postoperative infections, delayed deep infection, nonspecific inflammation, rejection, or fractures were encountered. At a mean follow-up of 5.3 years, the mean Musculoskeletal Tumor Society's (MSTS) 93 score was 29.3 points (range: 28-30 points) and mean radiopaque density ratio was 0.77±0.10. The radiologic analysis showed that porous n-HA/PA66 composite had been completely incorporated with the host bone about 1.5 years later. In conclusion, this study indicated that the porous n-HA/PA66 composite had biological safety, and good biocompatibility, osteoinduction, and osseointegration. Thus, the porous n-HA/PA66 composite is an ideal artificial bone substitute and worthy of promotion in the field. PMID:24531621

  6. Fractal analysis of lyotropic lamellar liquid crystal textures

    NASA Astrophysics Data System (ADS)

    Muniandy, S. V.; Kan, C. S.; Lim, S. C.; Radiman, S.

    2003-05-01

    We apply fractal analysis to study the birefringence textures of lyotropic lamellar liquid crystal system (water/cethylpyridinium chloride/decanol). Birefringence texture morphologies are important as they provide information on the molecular ordering as well as defect structures and therefore has been adopted as a standard method in characterizing different phases of liquid crystals. The system under consideration shows a gradual morphological transition from mosaic to oily streak structures and then to maltese cross texture when the water content is increased. Since these textures are the characteristic fingerprints for the lyotropic lamellar phases, it is necessary to have robust techniques to obtain image quantifiers that can characterize the morphological structure of the textures. For this purpose we employ three different approaches namely the Fourier power spectrum for monofractal analysis, the generalized box-counting method for multifractal analysis and multifractal segmentation technique for estimating the space-varying local Hurst exponents. The relationships between estimated image parameters such as the spectral exponent, the Hurst exponent and the fractal dimension with respect to patterns observed in the birefringence textures are discussed.

  7. Tectonic Lamellar Keratoplasty Using Cryopreserved Cornea in a Large Descemetocele

    PubMed Central

    Kim, Kang Yoon; Jung, Ji Won; Kim, Eung Kweon; Seo, Kyoung Yul

    2016-01-01

    We describe herein a case of an impending corneal perforation with a large descemetocele in a patient with previous penetrating keratoplasty (PKP) that subsequently was treated with an emergent lamellar keratoplasty using frozen preserved cornea. A 76-year-old male patient, who had a PKP, presented with a completely whitish and edematous graft accompanied by large epithelial defects. Although antibiotics and antiviral agents were tried for three days, the corneal stroma abruptly melted, except for the Descemet's membrane and endothelium. Cryopreserved corneal tissue that was kept at -80? was thawed and sutured on top of the remaining Descemet's membrane and endothelium. Pathological and microbiological tests were conducted using the remaining donor and recipient corneal tissues. After tectonic corneal transplantation on top of a large descemetocele, a healthy graft and relatively clear interfaces between graft-host junctions were maintained without serious adverse reactions throughout 6 month follow-up period. Microbiological evaluations of donor tissue at the time of thawing and tissue preparation were done, and the results were all negative. Tissue that was taken intraoperatively from the recipient cornea also showed negative microbiological results. In conclusion, tectonic lamellar keratoplasty, using cryopreserved corneal tissue, only onto the remaining Descemet's membrane and endothelium in an emergent condition, was a safe and effective treatment. PMID:26632412

  8. Tectonic Lamellar Keratoplasty Using Cryopreserved Cornea in a Large Descemetocele.

    PubMed

    Kim, Kang Yoon; Jung, Ji Won; Kim, Eung Kweon; Seo, Kyoung Yul; Kim, Tae Im

    2016-01-01

    We describe herein a case of an impending corneal perforation with a large descemetocele in a patient with previous penetrating keratoplasty (PKP) that subsequently was treated with an emergent lamellar keratoplasty using frozen preserved cornea. A 76-year-old male patient, who had a PKP, presented with a completely whitish and edematous graft accompanied by large epithelial defects. Although antibiotics and antiviral agents were tried for three days, the corneal stroma abruptly melted, except for the Descemet's membrane and endothelium. Cryopreserved corneal tissue that was kept at -80°C was thawed and sutured on top of the remaining Descemet's membrane and endothelium. Pathological and microbiological tests were conducted using the remaining donor and recipient corneal tissues. After tectonic corneal transplantation on top of a large descemetocele, a healthy graft and relatively clear interfaces between graft-host junctions were maintained without serious adverse reactions throughout 6 month follow-up period. Microbiological evaluations of donor tissue at the time of thawing and tissue preparation were done, and the results were all negative. Tissue that was taken intraoperatively from the recipient cornea also showed negative microbiological results. In conclusion, tectonic lamellar keratoplasty, using cryopreserved corneal tissue, only onto the remaining Descemet's membrane and endothelium in an emergent condition, was a safe and effective treatment. PMID:26632412

  9. Lamellar coupled growth in the neopentylglycol-(D)camphor eutectic

    NASA Astrophysics Data System (ADS)

    Witusiewicz, V. T.; Sturz, L.; Hecht, U.; Rex, S.

    2014-01-01

    Lamellar eutectic growth was investigated in the transparent organic alloy neopentylglycol-(D)camphor of eutectic composition (NPG-45.3 wt% DC) using bulk (3D) and thin (2D) samples. Two types of eutectic grains were observed in the polycrystalline samples, either with lamellae well aligned to the direction of solidification or inclined at an angle of 21.5±1.5°. The well aligned grains were used for determining lamellar spacing as function of growth velocity V and temperature gradient G. Based on these data the Jackson-Hunt constant was evaluated to be KJH=1.60±0.15 ?m3 s-1. For low growth velocity experiments the contact angles for (DC) and (NPG) lamellae at eutectic triple junctions were also evaluated, being ?(DC)=50.9±4.1° and ?(NPG)=41.8±4.7°, respectively. Using these values, as well as phase diagram data and the Gibbs-Thomson coefficients, the chemical coefficient of diffusion of (D)camphor in the eutectic liquid at eutectic temperature 53 °C was estimated to be DL=97±15 ?m2 s-1.

  10. Lamellar diblock copolymer grain boundary morphology. 1. Twist boundary characterization

    SciTech Connect

    Gido, S.P.; Gunther, J.; Thomas, E.L. . Dept. of Materials Science and Engineering); Hoffman, D. . Dept. of Mathematics and Statistics)

    1993-08-16

    Grain boundary morphologies in poly(styrene-b-butadiene) lamellar diblock copolymers were characterized using transmission electron microscopy (TEM). Two types of twist grain boundaries were observed in which microphase separation of the two blocks was maintained in the grain boundary region by intermaterial dividing surfaces that approximate classically known minimal surfaces. The geometry of these interfaces was demonstrated by comparing experimental TEM images with ray tracing computer simulations of the model surfaces as the projection direction was systematically varied in both the experimental and simulated images. The two morphologies observed were found to have intermaterial dividing surfaces that approximate either Scherk's first (doubly periodic) surface or a section of the right helicoid. The helicoid section boundary was observed at low twist angles, less than or equal to about 15. The Scherk surface family of boundary morphologies, which consists of a doubly periodic array of saddle surfaces, was found over the entire twist range from 0 to 90[degree]. As the twist angle approaches 0[degree] the Scherk surface grain boundary morphology is transformed into a single screw dislocation that has an intermaterial dividing surface with the geometry of a single helicoid. Direct TEM imaging of the detailed core structure of this screw dislocation is presented. These images demonstrate that in the lamellar diblock copolymer the screw dislocation core is nonsingular. This nonsingular core structure represents a radical departure from the singular core structures observed in classical studies of dislocations in atomic crystals.

  11. Anomalous birefringence of swollen lamellar phases : blue smectics

    NASA Astrophysics Data System (ADS)

    Nallet, F.; Barois, Ph.

    1994-06-01

    The birefringence of a lyotropic lamellar phase is calculated as a function of dilution. It is found to vanish and change sign, provided the natural birefringence of surfactant bilayers is positive. Dispersion is calculated about the point of zero birefringence. These predictions are illustrated with experiments of spectrophotometry: the intensity of light transmitted between crossed polarizers through several lamellar samples vanishes as expected at some particular wavelength. The dependence of the transmitted light on wavelength and cell thickness is consistent with theory. La biréfringence d'une phase lamellaire lyotrope est calculée en fonction de la dilution. Nous montrons qu'elle peut s'annuler à condition que la biréfringence naturelle des bicouches de tensioactif soit positive. La dispersion au voisinage du point de biréfringence nulle est calculée. Ces résultats sont confirmés par des mesures de spectrophotométrie : la transmission des échantillons étudiés entre polariseurs croisés s'annule exactement pour une longueur d'onde particulière. La variation de l'intensité transmise en fonction de la longueur d'onde et de l'épaisseur des échantillons est conforme aux prévisions du modèle.

  12. Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations Using sfx Mice and BXD RI Strains

    PubMed Central

    Huang, Yue; Zhu, Xiaodong; Wang, Lishi; Liu, Xiaoyun; Lu, Lu; Jiao, Yan

    2014-01-01

    The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference. PMID:25133246

  13. Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells.

    PubMed

    Gao, Guifang; Schilling, Arndt F; Yonezawa, Tomo; Wang, Jiang; Dai, Guohao; Cui, Xiaofeng

    2014-10-01

    Bioprinting based on thermal inkjet printing is a promising but unexplored approach in bone tissue engineering. Appropriate cell types and suitable biomaterial scaffolds are two critical factors to generate successful bioprinted tissue. This study was undertaken in order to evaluate bioactive ceramic nanoparticles in stimulating osteogenesis of printed bone marrow-derived human mesenchymal stem cells (hMSCs) in poly(ethylene glycol)dimethacrylate (PEGDMA) scaffold. hMSCs suspended in PEGDMA were co-printed with nanoparticles of bioactive glass (BG) and hydroxyapatite (HA) under simultaneous polymerization so the printed substrates were delivered with highly accurate placement in three-dimensional (3D) locations. hMSCs interacted with HA showed the highest cell viability (86.62 ± 6.02%) and increased compressive modulus (358.91 ± 48.05 kPa) after 21 days in culture among all groups. Biochemical analysis showed the most collagen production and highest alkaline phosphatase activity in PEG-HA group, which is consistent with gene expression determined by quantitative PCR. Masson's trichrome staining also showed the most collagen deposition in PEG-HA scaffold. Therefore, HA is more effective comparing to BG for hMSCs osteogenesis in bioprinted bone constructs. Combining with our previous experience in vasculature, cartilage, and muscle bioprinting, this technology demonstrates the capacity for both soft and hard tissue engineering with biomimetic structures. PMID:25130390

  14. Bending moduli of a nonadsorbing-polymer-containing lyotropic lamellar phase: An experimental study

    NASA Astrophysics Data System (ADS)

    Bouglet, G.; Ligoure, C.; Bellocq, A. M.; Dufourc, E.; Mosser, G.

    1998-01-01

    We investigate the effect of the incorporation of a neutral water-soluble nonadsorbing polymer polyvinylpyrrolidone (PVP) on the bilayer bending moduli ? and ?¯ of the lamellar phase L? composed of cetylpiridiniumchloride (CPCL)/hexanol/H2O. The mean bending modulus ? is obtained from the measurement of quadrupolar splittings of perdeuterated hexanol by deuterium solid state NMR. It is found that ? is insensitive to the amount of polymer in the lamellar phase, in agreement with the theoretical predictions. Observations with the polarizing microscope of topological defects in the lamellar phase allow a qualitative study of the Gaussian bending modulus ?¯. Addition of a small amount of polymer in the lamellar phase induces a large proliferation of focal conic domains of second species (positive Gaussian curvature). Cryo-TEM confirms that the polymer drastically modify the texture of the lamellar phase. These results indicate clearly that the presence of the nonadsorbing polymer strongly decreases ?¯, in contradiction with theoretical predictions.

  15. [Bone and Nutrition. Sclerostin and bone metabolism].

    PubMed

    Tatsumi, Sawako; Nagamoto, Kenta; Ogata, Mao; Miyamoto, Ken-ichi

    2015-07-01

    Osteocytes orchestrate bone resorption and bone formation by controlling osteoclast and osteoblast activity. On the other hand, osteocytes secret FGF23 (fibroblast growth factor 23), FGF23 acts on the kidney to control phosphate homeostasis. Sclerostin is also released from osteocytes and it regulated osteoblast activity through Wnt/?-catenin pathway. Therefore, an antibody that targets sclerostin is currently in phase- III clinical trials for the treatment of osteoporosis and it is expected as new therapeutics. PMID:26119318

  16. Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

    PubMed Central

    Spector, Tim D; Calomme, Mario R; Anderson, Simon H; Clement, Gail; Bevan, Liisa; Demeester, Nathalie; Swaminathan, Rami; Jugdaohsingh, Ravin; Berghe, Dirk A Vanden; Powell, Jonathan J

    2008-01-01

    Background Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial. Methods Over 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 ?g cholecalciferol (Vit D3) and three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. Bone formation markers in serum and urinary resorption markers were measured at baseline, and after 6 and 12 months. Femoral and lumbar BMD were measured at baseline and after 12 months by DEXA. Results Overall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP) was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo) without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I). Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur < -1) however was significant for the 6 mg dose at the femoral neck (T-test). There were no ch-OSA related adverse events observed and biochemical safety parameters remained within the normal range. Conclusion Combined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis. NTR 1029 PMID:18547426

  17. Equation of state of a charged bilayer system: Measure of the entropy of the lamellar-lamellar transition in DDABr

    NASA Astrophysics Data System (ADS)

    Dubois, M.; Zemb, Th.; Fuller, N.; Rand, R. P.; Parsegian, V. A.

    1998-05-01

    The synthetic cationic double-chain surfactant didodecyldimethylammonium bromide shows two distinct thermodynamically stable lamellar phases; a dilute L? phase stabilized predominantly by electrostatic forces, and a condensed L?' phase stabilized by "hydration" forces. Using six different experimental methods, applying osmotic stress from 102 to 109Pa and varying temperature from 20 °C to 70 °C, we have measured the osmotic pressure vs interbilayer distance and thus mapped the phase diagram with an equation of state. In this binary system, the area per headgroup as well as bilayer thickness vary with concentration and temperature. Hence, lateral compressibility has to be taken into account in the free energy balance. The osmotic stress needed to effect the swollen-to-collapsed lamellar phase transition is determined as a function of temperature. From these data the entropy of the L?-L?' transition is found to be a strong function of temperature. Below 40 °C, condensation from the dilute L? phase, the change of entropy is negative as might be expected. Above 40 °C the entropy of condensation is positive, demonstrating that there is a release of degrees of freedom associated with the bilayer condensation. These data allow us to think far more critically about the forces that stabilize bilayer systems.

  18. A Novel Murine Elastase Saccular Aneurysm Model for Studying Bone Marrow Progenitor-Derived Cell–Mediated Processes in Aneurysm Formation

    PubMed Central

    Hoh, Brian L.; Velat, Gregory J.; Wilmer, Erin N.; Hosaka, Koji; Fisher, Robert C.; Scott, Edward W.

    2010-01-01

    BACKGROUND Although there are several large-species animal models for saccular aneurysms, there is a need for a simple, reproducible saccular aneurysm model in mice. OBJECTIVE To develop a murine saccular aneurysm model, which replicates key characteristics that occur in the formation of human cerebral aneurysms. METHODS Elastase is applied extravascularly to the right common carotid artery. We induced saccular aneurysm formation by our method in C57BL/6 mice (n = 30). Aneurysms and control arteries (left common carotid arteries) were harvested at 1 week, 2 weeks, and 3 weeks postinjury (n = 10 for each time point), measured, and stained for elastin content. To demonstrate BMP-derived cell recruitment to the aneurysms, bone marrow from UBC-gfp transgenic mice was transplanted into irradiated C57BL/6 recipients to create C57BL/6.gfp chimeras. Additionally, bone marrow from DsRed transgenic mice was transplanted into irradiated C57BL/6 recipients to create C57BL/6.DsRed chimeras, and bone marrow from B5/EGFP transgenic mice was transplanted into irradiated FVB recipients to create FVB.gfp chimeras. The elastase injury or sham operations were performed in the C57BL/6.gfp, C57BL/6.DsRed, and FVB.gfp chimeras. Aneurysms and sham vessels were harvested at 3 weeks and examined for BMP-derived cell recruitment. Additionally, aneurysms were stained for matrix metalloproteinase-9, which is overexpressed in human cerebral aneurysm tissue. RESULTS Aneurysms consistently demonstrated significant loss of elastin in the vessel wall and had significantly larger diameters than control vessels (591 ± 238 µm vs 328 ± 61µm; P = .003 for aneurysms 3 weeks postinjury). Aneurysms from C57BL/6.gfp, FVB.gfp, and C57BL/6.DsRed chimeras consistently revealed significant BMP-derived cell recruitment in the aneurysm wall that was not seen in sham-operated vessels nor in control left common carotid arteries. Aneurysms demonstrated overexpression of matrix metalloproteinase-9. CONCLUSION We describe a novel murine elastase saccular aneurysm model that replicates the histopathology and BMP-derived cell–mediated processes that will be a valuable instrument for studying the cell-mediated processes in cerebral aneurysm formation. PMID:20173550

  19. Bone quality and bone strength: benefits of the bone-forming approach

    PubMed Central

    Iolascon, Giovanni; Frizzi, Laura; Di Pietro, Gioconda; Capaldo, Annarita; Luciano, Fabrizio; Gimigliano, Francesca

    2014-01-01

    Summary The ability of bone to resist fracture depends on the intrinsic properties of the materials that comprise the bone matrix mineralization, the amount of bone (i.e. mass), and the spatial distribution of the bone mass (i.e. microarchitecture). Antiresorptive agents may prevent the decay of cancellous bone and cortical thinning, with no improvement of bone microstructure, leading to a partial correction of the principal bone quality defect in osteoporosis, the disruption of trabecular microarchitecture. Anabolic agents promote bone formation at both trabecular and endocortical surfaces, resulting in an increase of cancellous bone volume and cortical thickness. The improvement of cortical bone strength may be limited by an increase in cortical porosity. strontium ranelate improves trabecular network and cortical thickness that will contribute to anti-fracture efficacy at both vertebral and non-vertebral sites. The results of clinical and experimental studies are consistent with the mode of action of strontium involving dissociation between bone formation and resorption leading to a stimulation both trabecular and cortical bone formation without increasing cortical porosity. PMID:25002875

  20. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    PubMed Central

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. PMID:26247020

  1. Constitutive laws and failure models for compact bones subjected to dynamic loading.

    PubMed

    Pithioux, M; Chabrand, P; Jean, M

    2002-10-01

    Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra- and macro-structures. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0, 45 and 90 degrees to the longitudinal axis of the bone and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model. PMID:12745432

  2. A defect mediated lamellar to isotropic transition of amphiphile bilayers

    E-print Network

    Antara Pal; Georg Pabst; V. A. Raghunathan

    2011-11-25

    We report the observation of a novel isotropic phase of amphiphile bilayers in a mixed system consisting of the ionic surfactant, sodium docecylsulphate (SDS), and the organic salt p-toludine hydrochloride (PTHC). This system forms a collapsed lamellar ($L_\\alpha$) phase over a wide range of water content, which transforms into an isotropic phase on heating. This transition is not observed in samples without excess water, where the $L_\\alpha$ phase is stable at higher temperatures. Our observations indicate that the $L_\\alpha$ - isotropic transition is driven by the unbinding of edge dislocation loops and that the isotropic phase in the present attraction-dominated system is the analogue of the sponge phase usually seen in amphiphile systems dominated by interbilayer steric repulsion.

  3. A new lamellar wound configuration for penetrating keratoplasty surgery.

    PubMed

    Busin, Massimo

    2003-02-01

    A modified penetrating keratoplasty procedure with a new lamellar configuration of the surgical wound was performed on 8 eyes with endothelial decompensation. This technique allows complete suture removal by 3 months postoperatively, substantially shortening the time necessary for visual rehabilitation. Refractive astigmatism before and after suture removal was minimized to 4 diopters or less in all of the eyes in our preliminary series. Because the anterior surface of the donor button is smaller than the posterior one (diameter, 7.0 mm and 9.0 mm, respectively), more endothelial cells can be transplanted while maintaining the anterior graft surface at a safe distance from the corneoscleral limbus. Finally, no expensive instrumentation is required for this procedure except for an artificial anterior chamber if whole globes are not available. The surgical technique and clinical results are presented in this article. PMID:12583794

  4. Defect-mediated lamellar-isotropic transition of amphiphile bilayers

    NASA Astrophysics Data System (ADS)

    Pal, Antara; Pabst, Georg; Raghunathan, V. A.

    We report the observation of a novel isotropic phase of amphiphile bilayers in a mixed system consisting of the ionic surfactant, sodium docecylsulphate (SDS), and the organic salt p-toludine hydrochloride (PTHC). This system forms a collapsed lamellar ($L_\\alpha$) phase over a wide range of water content, which transforms into an isotropic phase on heating. This transition is not observed in samples without excess water, where the $L_\\alpha$ phase is stable at higher temperatures. Our observations indicate that the $L_\\alpha$ - isotropic transition is driven by the unbinding of edge dislocation loops and that the isotropic phase in the present attraction-dominated system is the analogue of the sponge phase usually seen in amphiphile systems dominated by interbilayer steric repulsion.

  5. The stability of lamellar gamma-gamma-prime structures. [nickel-base superalloy

    NASA Technical Reports Server (NTRS)

    Nathal, M. V.; Mackay, R. A.

    1987-01-01

    The stability of stress-annealed gamma/gamma-prime lamellar structures were investigated using three nickel-base single-crystal alloys (the NASAIR 100 and two similar alloys, E and F, containing 5 and 10 wt pct Co, respectively) stress-annealed at 1000 C to form lamellae perpendicular to the applied stress. The rate of the lamellar thickening under various thermal and creep exposures was examined by SEM. For unstressed aging at 1100 C, the lamellar structures of the NASAIR and the E alloys exhibited continuous but slow lamellar coarsening, whereas the lamellae of the alloy F showed pronounced thickening plus spheroidization. Resistance to lamellar thickening was correlated with high magnitudes of lattice mismatch, which promoted a more regular lamellar structure and a finer spacing of misfit dislocations. Specimens which were tension-annealed prior to compressive creep testing exhibited an earlier onset of tertiary creep in comparison with only heat-treated specimens. This was associated with accelerated lamellar coarsening in the stress-annealed specimens.

  6. Bone Cancer

    MedlinePLUS

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  7. Bone taphonomy of the Schöningen "Spear Horizon South" and its implications for site formation and hominin meat provisioning.

    PubMed

    Starkovich, Britt M; Conard, Nicholas J

    2015-12-01

    This paper presents the faunal remains from the new excavation area at the Lower Paleolithic site of Schöningen. The focus of the study is on the southern extension of the main find horizon (Spear Horizon South), which includes the layer that yielded the famous Schöningen spears (13 II-4). Taxonomic data corroborate previous studies, that hominins primarily hunted Equus mosbachensis, a large Pleistocene horse. Equid body part representation at the site suggests that the animals were hunted and butchered locally. There is no evidence for density-mediated attrition in the assemblage. Weathering damage is uncommon, though there is ample evidence that carnivores had access to the bone. Carnivore bite sizes were measured and compared to experimental data provided by previous authors. Based on relationships between bite size and carnivore behavior and body size, we conclude that the primary modifying agents were large carnivores (i.e., wolves or saber-toothed cats). Previous studies show that carnivores often had secondary access to the remains, after hominins. Cut marks are commonly arranged haphazardly on the bones. This may indicate that multiple hominins participated in the butchery of horse skeletons, or that they were butchered over the course of hours or days. Cut marks on axial elements are more "orderly," which probably reflects the physical logistics of orienting one's body in relation to a large carcass. These data differ from sites formed by Middle and Upper Paleolithic hominins, which might suggest that in later times, a system of organized meat provisioning was already in place. Taken together, the faunal evidence from the Spear Horizon South indicates that late Lower Paleolithic hominins using the site understood the behaviors of different prey species, hunted socially to take down large game, and successfully competed with large carnivores on the landscape for primary access to ungulate remains. PMID:26626957

  8. 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-? family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-?, and third IGF-I. TGF-? enhances bone formation mainly by intramembranous ossification in vivo. TGF-? affects both cell proliferation and differentiation, however, TGF-? mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-? is increased by estrogen(E 2), androgen, vitamin D, TGF-? 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.

  9. Effect of nano-hydroxyapatite on bone morphogenetic protein-2-induced hard tissue formation and dentin resorption on a dentin surface

    NASA Astrophysics Data System (ADS)

    Tamagawa, Hiroki; Tenkumo, Taichi; Sugaya, Tsutomu; Kawanami, Masamitsu

    2012-12-01

    AimThe purpose of this study was to evaluate the effects of the addition of nano-hydroxyapatite to a collagen membrane-carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) on hard tissue formation and dentin resorption on dentin surfaces in vivo. Materials and methodsNano-hydroxyapatite collagen composite (nHAC) membranes or collagen (C) membranes were each immersed in either 100 or 400 ?g/ml rhBMP-2 and placed on dentin chips that were implanted into rat thigh muscle. The implants were analyzed at 2 or 4 weeks after surgery by histological observation and histomorphometric analysis. ResultsThe percentage of the hard tissue formed by each nHAC group was significantly higher than that formed by any of the C groups, except for that formed by the group loaded with 400 ?g/ml rhBMP-2 at 4 weeks after implantation. No significant differences were observed in the percentage of dentin resorption between the nHAC groups and C groups at any stage or at any rhBMP-2 concentration. ConclusionThese findings showed that addition of nano-hydroxyapatite to a collagen membrane accelerated the formation of hard tissue induced by a low dose of rhBMP-2 on dentin surfaces at an early stage after implantation into rat thigh muscle, without increasing dentin resorption.

  10. Mineralized three-dimensional bone constructs

    NASA Technical Reports Server (NTRS)

    Clarke, Mark S. F. (Inventor); Sundaresan, Alamelu (Inventor); Pellis, Neal R. (Inventor)

    2011-01-01

    The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts and osteoclast precursors under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics.

  11. Mineralized Three-Dimensional Bone Constructs

    NASA Technical Reports Server (NTRS)

    Clarke, Mark S. F. (Inventor); Sundaresan, Alamelu (Inventor); Pellis, Neal R. (Inventor)

    2013-01-01

    The present disclosure provides ex vivo-derived mineralized three-dimensional bone constructs. The bone constructs are obtained by culturing osteoblasts and osteoclast precursors under randomized gravity vector conditions. Preferably, the randomized gravity vector conditions are obtained using a low shear stress rotating bioreactor, such as a High Aspect Ratio Vessel (HARV) culture system. The bone constructs of the disclosure have utility in physiological studies of bone formation and bone function, in drug discovery, and in orthopedics.

  12. Characterization of diblock copolymer lamellar structure from neutron scattering measurements and molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Jeong, Cheol; Kim, Jenny; Kim, Sangcheol; Tsai, Tsung-Han; Coughlin, E. Brian; Soles, Christopher

    2015-03-01

    The Nanoscale structure of block copolymers (BCP) with lamellar morphology plays an important role in transport properties for fuel cell and battery application. We develop a paracrystalline model to interpret small angle neutron scattering (SANS) and X-ray scattering (SAXS) data of hydrated amphiphilic BCP lamellar phase in order to elucidate water distribution as well as hydrophilic and hydrophobic domain spacing. We assume Gamma distribution for the fluctuation of lamellar thickness instead of Gaussian. It is observed that BCP can deswell upon hydration along lamellar normal direction due to chain collapse of hydrophobic domain overcoming expansion of hydrophilic domain, which has been compared with coarse-grained molecular dynamics simulation (CGMD). CGMD results show that the variation of interfacial area per chain is strongly correlated to the conformation of hydrophobic chains, domain spacing and water distribution in the hydrophilic domain, compatible with the observation from SANS and SAXS.

  13. Bone impairment in oxalosis: An ultrastructural bone analysis.

    PubMed

    Bacchetta, Justine; Farlay, Delphine; Abelin-Genevois, Kariman; Lebourg, Ludivine; Cochat, Pierre; Boivin, Georges

    2015-12-01

    Deposition of calcium oxalate crystals in the kidney and bone is a hallmark of systemic oxalosis. Since the bone compartment can store massive amounts of oxalate, patients present with recurrent low-trauma fractures, bone deformations, severe bone pains and specific oxalate osteopathy on plain X-ray. Bone biopsy from the iliac crest displays specific features such as oxalate crystals surrounded by a granulomatous reaction due to an invasion of bone surface by macrophages. We present data obtained in 10 samples from 8 patients with oxalosis (16-68years) who underwent iliac crest bone biopsy and bone quality analysis using modern methods (microradiography, microindentation, Fourier Transform InfraRed Microspectroscopy, transmission electron microscopy) in addition to histomorphometry. Disseminated calcium oxalate deposits (whewellite) were found in the bone marrow space (with a granulomatous reaction) but not in the bone matrix. Calcium oxalate deposits were totally surrounded by macrophages and multinucleated giant cells, and a phagocytosis activity was sometimes observed. Very few calcium oxalate crystals were directly in close contact with the mineral substance of the bone. Bone mineralization was not modified by the presence of calcium oxalate even in close vicinity. Bone quality analysis also revealed a harder bone than normal, perhaps in relationship with decreased carbonate content in the mineral. This increase in bone hardness could explain a more "brittle" bone. In patients with oxalosis, the formation and growth of calcium oxalate crystals in the bone appeared independent of apatite. The mechanisms leading to nucleation and growth of oxalate deposits are still unclear and deserve further studies. PMID:26164477

  14. Diffusion Coefficients in a Lamellar Lyotropic Phase: Evidence for Defects Connecting the Surfactant Structure

    E-print Network

    Doru Constantin; Patrick Oswald

    2015-04-09

    We measure diffusion coefficients in the lamellar phase of the nonionic binary system C$_{12}$EO$_6$/H$_2$O using fluorescence recovery after photobleaching. The diffusion coefficient across the lamellae shows an abrupt increase upon approaching the lamellar-isotropic phase transition. We interpret this feature in terms of defects connecting the surfactant structure. An estimation of the defect density and of the variation in defect energy close to the transition is given in terms of a simple model.

  15. Derivation of inter-lamellar behaviour of the intervertebral disc annulus

    PubMed Central

    Mengoni, Marlène; Luxmoore, Bethany J.; Wijayathunga, Vithanage N.; Jones, Alison C.; Broom, Neil D.; Wilcox, Ruth K.

    2015-01-01

    The inter-lamellar connectivity of the annulus fibrosus in the intervertebral disc has been shown to affect the prediction of the overall disc behaviour in computational models. Using a combined experimental and computational approach, the inter-lamellar mechanical behaviour of the disc annulus was investigated under conditions of radial loading. Twenty-seven specimens of anterior annulus fibrosus were dissected from 12 discs taken from four frozen ovine thoracolumbar spines. Specimens were grouped depending on their radial provenance within the annulus fibrosus. Standard tensile tests were performed. In addition, micro-tensile tests under microscopy were used to observe the displacement of the lamellae and inter-lamellar connections. Finite elements models matching the experimental protocols were developed with specimen-specific geometries and boundary conditions assuming a known lamellar behaviour. An optimisation process was used to derive the interface stiffness values for each group. The assumption of a linear cohesive interface was used to model the behaviour of the inter-lamellar connectivity. The interface stiffness values derived from the optimisation process were consistently higher than the corresponding lamellar values. The interface stiffness values of the outer annulus were from 43% to 75% higher than those of the inner annulus. Tangential stiffness values for the interface were from 6% to 39% higher than normal stiffness values within each group and similar to values reported by other investigators. These results reflect the intricate fibrous nature of the inter-lamellar connectivity and provide values for the representation of the inter-lamellar behaviour at a continuum level. PMID:25955558

  16. Elasticity and hydrodynamic properties of ``doped solvent dilute'' lamellar phases

    NASA Astrophysics Data System (ADS)

    Nallet, Frédéric; Roux, Didier; Quilliet, Catherine; Fabre, Pascale; Milner, Scott T.

    1994-09-01

    The equilibrium fluctuations and weakly out-of-equilibrium relaxation properties of “doped solvent" dilute lamellar phases are investigated, both theoretically and experimentally, in the low-frequency, long-wavelength limit. The physical system of interest is a three-component smectic A lyotropic liquid crystal where surfactant bilayers infinite in extent are periodically stacked along one direction in space and separated by a colloidal solution. Two experimentally relevant modes are found in the lowest frequency part of the fluctuation spectrum of such multicomponent systems. Both are associated to the relaxation of coupled layer displacement and colloid concentration waves. In the limit of small coupling, one mode is close to the well-known undulation/baroclinic mode of two-component lamellar phases, while the other corresponds to the Brownian diffusive motion of the colloid in an anisotropic medium. Elastic constants of the smectic liquid crystal and diffusion parameters of the colloidal solution may be deduced from a measurement of the anisotropic dispersion relation of these two modes, as illustrated by dynamic light scattering experiments on the ferrosmectic system. Les fluctuations à l'équilibre ainsi que la relaxation des états légèrement en dehors de l'équilibre des phases lamellaires à “solvant dopé” sont étudiées, aussi bien d'un point de vue théorique qu'expérimental, dans la limite de basses fréquences et de grandes longueurs d'onde. Les systèmes décrits sont des cristaux-liquides smectiques A lyotropes formés de trois constituants : un tensioactif en solution dans une suspension colloïdale forme des bicouches de grande extension latérale qui s'empilent de façon périodique le long d'une direction dans l'espace. Avec de tels systèmes anisotropes et à plusieurs constituants deux modes présents dans la partie à basse fréquence du spectre des fluctuations (associés à la relaxation d'ondes, couplées, de concentration colloïdale et de déplacement des couches smectiques) ont une certaine importance expérimentale. Dans la limite d'un couplage faible, l'un des deux modes est similaire au mode barocline des phases lamellaires à deux constituants ; le second s'identifie au mouvement brownien de diffusion d'un colloïde dans un substrat anisotrope. Les constantes élastiques du cristal liquide smectique de même que le coefficient de diffusion du colloïde peuvent en principe être déduits de la mesure des relations anisotropes de dispersion de ces deux modes ; cela est illustré par des expériences de diffusion quasi-élastique de la lumière sur des ferrosmectiques.

  17. An in vivo evaluation of PLLA/PLLA-gHA nano-composite for internal fixation of mandibular bone fractures.

    PubMed

    Peng, Weihai; Zheng, Wei; Shi, Kai; Wang, Wangshu; Shao, Ying; Zhang, Duo

    2015-01-01

    Internal fixation of bone fractures using biodegradable poly(L-lactic-acid) (PLLA)-based materials has attracted the attention of many researchers. In the present study, 36 male beagle dogs were randomly assigned to two groups: PLLA/PLLA-gHA (PLLA-grafted hydroxyapatite) group and PLLA group. PLLA/PLLA-gHA and PLLA plates were embedded in the muscular bags of the erector spinae and also implanted to fix mandibular bone fractures in respective groups. At 1, 2, 3, 6, 9, and 12 months postoperatively, the PLLA/PLLA-gHA and PLLA plates were evaluated by adsorption and degradation tests, and the mandibles were examined through radiographic analysis, biomechanical testing, and histological analysis. The PLLA/PLLA-gHA plates were non-transparent and showed a creamy white color, and the PLLA plates were transparent and faint yellow in color. At all time points following surgery, adsorption and degradation of the PLLA/PLLA-gHA plates were significantly less than those of the PLLA plates, and the lateral and longitudinal bending strengths of the surgically treated mandibles of the beagle dogs in the PLLA/PLLA-gHA group were significantly greater than those of the PLLA group and reached almost the value of intact mandibles at 12 months postoperatively. Additionally, relatively rapid bone healing was observed in the PLLA/PLLA-gHA group with the formation of new lamellar bone tissues at 12 months after the surgery. The PLLA/PLLA-gHA nano-composite can be employed as a biodegradable material for internal fixation of mandibular bone fractures. PMID:26551378

  18. Lecithin based lamellar liquid crystals as a physiologically acceptable dermal delivery system for ascorbyl palmitate.

    PubMed

    Gosenca, Mirjam; Bešter-Roga?, Marija; Gašperlin, Mirjana

    2013-09-27

    Liquid crystalline systems with a lamellar structure have been extensively studied as dermal delivery systems. Ascorbyl palmitate (AP) is one of the most studied and used ascorbic acid derivatives and is employed as an antioxidant to prevent skin aging. The aim of this study was to develop and characterize skin-compliant dermal delivery systems with a liquid crystalline structure for AP. First, a pseudoternary phase diagram was constructed using Tween 80/lecithin/isopropyl myristate/water at a Tween 80/lecithin mass ratio of 1/1, and the region of lamellar liquid crystals was identified. Second, selected unloaded and AP-loaded lamellar liquid crystal systems were physicochemically characterized with polarizing optical microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheology techniques. The interlayer spacing and rheological parameters differ regarding quantitative composition, whereas the microstructure of the lamellar phase was affected by the AP incorporation, resulting either in additional micellar structures (at 25 and 32 °C) or being completely destroyed at higher temperature (37°C). After this, the study was oriented towards in vitro cytotoxicity evaluation of lamellar liquid crystal systems on a keratinocyte cell line. The results suggest that the lamellar liquid crystals that were developed could be used as a physiologically acceptable dermal delivery system. PMID:23643736

  19. Clear Zone Formation around Screws in the Early Postoperative Stages after Posterior Lumbar Fusion Using the Cortical Bone Trajectory Technique

    PubMed Central

    Iwatsuki, Koichi; Ohnishi, Yu-Ichiro; Ohkawa, Toshika; Yoshimine, Toshiki

    2015-01-01

    Study Design Retrospective study. Purpose To evaluate the initial fixation using the cortical bone trajectory (CBT) technique for posterior lumbar fusion through assessment of the clear zones around the screws and the risk factors involved. Overview of Literature Postoperative radiolucent zones (clear zones) are an indicator of poor conventional pedicle screw fixation. Methods Between January 2013 and April 2014, 19 patients (8 men and 11 women) underwent posterior lumbar interbody fusion or posterior lumbar fusion using the CBT technique. A total of 109 screws were used for evaluation with measurement of the maximum insertional torque of last two screw rotations. Clear zone-positivity on plain radiographs was investigated 6 months after surgery. The relation between intraoperative insertional torque and clear zone-positivity was investigated by one-way analysis of variance. In addition, the correlation between clear zone-positivity and gender, age (<75 years old or >75 years old), or operative stabilization level (<2 or >3 vertebral levels) was evaluated using the chi-square test. Results Clear zones were observed around six screws (5.50%) in five patients (26.3%). The mean insertional torque (4.00±2.09 inlbs) of clear zone-positive screws was lower than that of clear zone-negative screws (8.12±0.50 in-lbs), but the difference was not significant. There was a significant correlation between clear zone-positivity and operative level of stabilization. Conclusions The low incidence of clear zone-positive screws indicates good initial fixation using the CBT technique. Multilevel fusions may be risk factors for clear zone generation. PMID:26713120

  20. The response of bone to unloading

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with the expectation that such understanding will lead to effective treatment for disuse osteoporosis.

  1. Thermal and hydrodynamic effects in the ordering of lamellar fluids

    E-print Network

    G. Gonnella; A. Lamura; A. Tiribocchi

    2011-02-15

    Phase separation in a complex fluid with lamellar order has been studied in the case of cold thermal fronts propagating diffusively from external walls. The velocity hydrodynamic modes are taken into account by coupling the convection-diffusion equation for the order parameter to a generalised Navier-Stokes equation. The dynamical equations are simulated by implementing a hybrid method based on a lattice Boltzmann algorithm coupled to finite difference schemes. Simulations show that the ordering process occurs with morphologies depending on the speed of the thermal fronts or, equivalently, on the value of the thermal conductivity {\\xi}. At large value of {\\xi}, as in instantaneous quenching, the system is frozen in entangled configurations at high viscosity while consists of grains with well ordered lamellae at low viscosity. By decreasing the value of {\\xi}, a regime with very ordered lamellae parallel to the thermal fronts is found. At very low values of {\\xi} the preferred orientation is perpendicular to the walls in d = 2, while perpendicular order is lost moving far from the walls in d = 3.

  2. Lamellar ichthyosis maps to chromosome 14q11

    SciTech Connect

    Russell, L.J.; Compton, J.G.; Bale, S.J.

    1994-09-01

    Lamellar ichthyosis (LI) is a serious skin disorder inherited as an autosomal recessive trait and characterized by large, brown plate-like scales covering the body. Skin involvement is apparent at birth, often as a collodion membrane. Scarring alopecia, ectropion, and secondary hypohidrosis are frequent. We used a panel of candidates genes that are expressed in the epidermis to study seven multiplex Caucasian families in the U.S. and six inbred (multiplex and simplex) families in Egypt. We find no recombination (Z=9.11 at {theta}=0) in either set of families with transglutaminse 1 (TGM1), the gene encoding the enzyme responsible for cross-linking proteins to the cell envelope in the upper-most layer of the epidermis. In addition, striking homozygosity is observed in the inbred families for markers neighboring TGM1, defining a 9.3 cM candidate region which is bounded by MYH7 and D14S275. This is the first report of linkage in LI and suggests that further study of the TGM1 gene may identify the underlying pathogenesis of this severe, disfiguring disorder. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families.

  3. Rechargeable 3 V Li cells using hydrated lamellar manganese oxide

    SciTech Connect

    Bach, S.; Pereira-Ramos, J.P.; Baffier, N.

    1996-11-01

    The synthesis and the electrochemical features of hydrated lamellar manganese oxides are reported. The authors use the reduction of aqueous permanganate solution by fumaric acid and the oxidation of manganese hydroxide by an aqueous permanganate solution to obtain sol-gel birnessite and classical X-exchanged birnessites (X = Li, Al, Na), respectively. The high oxidation state of Mn associated with the 2D character of the hot lattice allows high specific capacities (150 to 200 Ah/kg) available in the potential range of 4 to 2 V. Interlayer water provides the structural stability of the host lattice required for long cycling. Rechargeable two-electrode Li cells using starved or flooded electrolytes were built with the cathodic materials. The batteries exhibit a satisfactory behavior with a specific capacity of 160 Ah/kg recovered after 30 cycles at the C/20 discharge-charge rate for the sol-gel birnessite. This paper demonstrates an interest in cathodic materials based on oxides containing structural water for use in secondary Li batteries.

  4. Numerical modeling of the cornea's lamellar structure and birefringence properties

    NASA Astrophysics Data System (ADS)

    Donohue, D. J.; Stoyanov, B. J.; McCally, R. L.; Farrell, R. A.

    1995-07-01

    A model of the cornea's lamellar structure is proposed that is capable of explaining experimental results obtained for the transmission of normal-incidence polarized light through rabbit and bovine cornea. The model consists of a large number of planar lamellae, each approximated as a uniaxial birefringent layer, stacked one upon another with various angular orientations. Polarized light transmission through the composite system is modeled theoretically by use of the Jones matrix formalism. The light transmission is calculated numerically for a large number of model lamellae arrangements, each generated from a statistical description, and histograms are constructed of various properties of the light transmission, including the minimum and maximum cross-polarized output intensities. It is demonstrated that various structural and optical parameters of the lamellae arrangements of actual corneas may be estimated by comparison of the calculations with detailed experimental data. Certain characteristics of the histograms are identified that permit a clear distinction between random and partially ordered systems. Comparisons with previously published experimental data provide strong evidence that the lamellae orientations are not entirely random, but rather a significant fraction are oriented in a fixed, preferred direction.

  5. Nanoscale lamellar photoconductor hybrids and methods of making same

    DOEpatents

    Stupp, Samuel I; Goldberger, Josh; Sofos, Marina

    2013-02-05

    An article of manufacture and methods of making same. In one embodiment, the article of manufacture has a plurality of zinc oxide layers substantially in parallel, wherein each zinc oxide layer has a thickness d.sub.1, and a plurality of organic molecule layers substantially in parallel, wherein each organic molecule layer has a thickness d.sub.2 and a plurality of molecules with a functional group that is bindable to zinc ions, wherein for every pair of neighboring zinc oxide layers, one of the plurality of organic molecule layers is positioned in between the pair of neighboring zinc oxide layers to allow the functional groups of the plurality of organic molecules to bind to zinc ions in the neighboring zinc oxide layers to form a lamellar hybrid structure with a geometric periodicity d.sub.1+d.sub.2, and wherein d.sub.1 and d.sub.2 satisfy the relationship of d.sub.1.ltoreq.d.sub.2.ltoreq.3d.sub.1.

  6. Intracorneal Rhinosporidiosis Managed with Deep Anterior Lamellar Keratoplasty

    PubMed Central

    Mukhopadhyay, Somnath; Datta, Himadri; Sen, Debanjan

    2014-01-01

    A healthy 22-year-old male presented to Institutional Cornea Clinic with an intracorneal mass overlying the pupil with lobulated edges having many tiny greyish white dots. The patient had a history of trauma while swimming in a pond with subsequent removal of intracorneal foreign body in the left eye approximately a year prior to presentation. Anterior segment optical coherence tomography (OCT) confirmed that an intracorneal mass sparing deep stroma and Descemet's membrane. A deep anterior lamellar keratoplasty (DALK) was performed in left eye and the mass was sent for histology examination. Histology evaluation was suggestive of rhinosporidiosis. The patient achieved 20/60 BCVA with -1.25 ?× 120° 1 year postoperatively without any evidence of recurrence at the graft-host interface. This unique presentation (as an ‘intracorneal mass’) of ocular rhinosporidiosis emphasizes that clinicians from our region of the world must consider rhinosporidiosis in the differential diagnosis especially with a history of penetrating injury while swimming in pond or river water. PMID:25371647

  7. Temporal response of bone to unloading

    SciTech Connect

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

    1986-02-01

    A model of weightlessness in which the hindlimbs of rats are elevated by their tails at a 40 degrees angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with /sup 45/Ca and (/sup 3/H)proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more /sup 45/Ca and (/sup 3/H)proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that 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 by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading.

  8. Lamellar Microstructure Alignment in Ti-47Al Alloy by Electromagnetic Confinement and Directional Solidification Using a Seed

    NASA Astrophysics Data System (ADS)

    Du, Yujun; Shen, Jun; Xiong, Yilong; Ren, Chunhe; Fu, Hengzhi

    2015-06-01

    As a promising electromagnetic process to obtain TiAl samples without contamination, electromagnetic confinement and directional solidification was successfully applied for lamellar microstructure control in Ti-47Al alloy. Seeded by a Ti-43Al-3Si seed, columnar ? grains grew stably and the lamellae within these grains were aligned parallel to the growth direction. However, stray ? or ? grains, in which the lamellae were complex, nucleated and grew in the sample edge. The possible reasons for the formation of stray grains were discussed by analyzing the temperature gradient at the solid/liquid interface and the macrosegregation of Ti5Si3 particles and Al solute along the sample radius. Moreover, the fluid flow induced by electromagnetic force, which led to the macrosegregation, was also discussed by using a simple model.

  9. Fluctuation Effects in AB/A/B Diblock Copolymer-Homopolymer Ternary Mixtures near the Lamellar-Disorder Transition

    NASA Astrophysics Data System (ADS)

    Gillard, Timothy; Hickey, Robert; Habersberger, Brian; Lodge, Timothy; Bates, Frank

    2015-03-01

    Fluctuations profoundly influence the phase behavior of block polymer-based soft materials. In ternary blends of an AB diblock copolymer with A- and B-type homopolymers, fluctuations destroy a mean-field predicted higher-order multicritical Lifshitz point and lead to the formation of the technologically important polymeric bicontinuous microemulsion phase (B ?E). Here we report a fascinating change in character of the lamellar-to-disorder phase transition as the composition of homopolymer in the ternary blend is increased from zero (neat diblock) to the onset of the B ?E channel. As the B ?E channel is approached, the transition exhibits increasingly second-order character with the development of large-scale fluctuating smectic correlations in the disordered state near the transition. This change in character of the transition is documented with a combination of scattering, optical transmission, rheology, and TEM experiments in model blends of poly(cyclohexylethylene- b-ethylene) with the constituent homopolymers.

  10. Bone grafts and their substitutes.

    PubMed

    Fillingham, Y; Jacobs, J

    2016-01-01

    The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):6-9. PMID:26733632

  11. Bone Metabolism on ISS Missions

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

    2014-01-01

    Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those that existed before space flight. Studies to assess bone strength after flight are underway at NASA, to better understand the results of bone remodeling. Studies are also underway to evaluate optimized exercise protocols and nutritional countermeasures. Regardless, there is clear evidence of progress being made to protect bone during spaceflight.

  12. miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway.

    PubMed

    Li, H; Li, T; Fan, J; Li, T; Fan, L; Wang, S; Weng, X; Han, Q; Zhao, R C

    2015-12-01

    Osteoporosis is a disease marked by reduced bone mass, leading to an increased risk of fractures or broken bones. Bone formation is mediated by recruiting mesenchymal stem cells (MSCs). Elucidation of the molecular mechanisms that regulate MSC differentiation into osteoblasts is of great importance for the development of anabolic therapies for osteoporosis and other bone metabolism-related diseases. microRNAs (miRNAs) have been reported to have crucial roles in bone development, osteogenic differentiation and osteoporosis pathophysiology. However, to date, only a few miRNAs have been reported to enhance osteogenesis and regulate the suppressive effect of glucocorticoids on osteogenic differentiation. In this study, we discovered that miR-216a, a pancreatic-specific miRNA, was significantly upregulated during osteogenic differentiation in human adipose-derived MSCs (hAMSCs). The expression of miR-216a was positively correlated with the expression of bone formation marker genes in clinical osteoporosis samples. Functional analysis demonstrated that miR-216a can markedly promote osteogenic differentiation of hAMSCs, rescue the suppressive effect of dexamethasone (DEX) on osteogenic differentiation in vitro and enhance bone formation in vivo. c-Cbl, a gene that encodes a RING finger E3 ubiquitin ligase, was identified as a direct target of miR-216a. Downregulation of c-Cbl by short hairpin RNAs can mimic the promotion effects of miR-216a and significantly rescue the suppressive effects of DEX on osteogenesis. Pathway analysis indicated that miR-216a regulation of osteogenic differentiation occurs via the c-Cbl-mediated phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The recovery effects of miR-216a on the inhibition of osteogenesis by DEX were attenuated after blocking the PI3K pathway. Thus, our findings suggest that miR-216a may serve as a novel therapeutic agent for the prevention and treatment of osteoporosis and other bone metabolism-related diseases. PMID:26206089

  13. Mechanistic aspects of fracture and R-curve behavior in elk antler bone

    SciTech Connect

    Launey, Maximilien E.; Chen, Po-Yu; McKittrick, Joanna; Ritchie, Robert O.

    2009-11-23

    Bone is an adaptative material that is designed for different functional requirements; indeed, bones have a variety of properties depending on their role in the body. To understand the mechanical response of bone requires the elucidation of its structure-function relationships. Here, we examine the fracture toughness of compact bone of elk antler which is an extremely fast growing primary bone designed for a totally different function than human (secondary) bone. We find that antler in the transverse (breaking) orientation is one of the toughest biological materials known. Its resistance to fracture is achieved during crack growth (extrinsically) by a combination of gross crack deflection/twisting and crack bridging via uncracked 'ligaments' in the crack wake, both mechanisms activated by microcracking primarily at lamellar boundaries. We present an assessment of the toughening mechanisms acting in antler as compared to human cortical bone, and identify an enhanced role of inelastic deformation in antler which further contributes to its (intrinsic) toughness.

  14. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    PubMed

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6?months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

  15. Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

    NASA Technical Reports Server (NTRS)

    Halloran, B.; Weider, T.; Morey-Holton, E.

    1999-01-01

    The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

  16. Atomistic studies of interactions between the dominant lattice dislocations and c/c-lamellar boundaries in lamellar c-TiAl

    E-print Network

    Paxton, Anthony T.

    in c-TiAl (ordinary screw 1 2 h110 and h1 0 1] superdislocations) with all three kinds of c of lamellar boundary controlled plastic deformation in PST TiAl. The interatomic inter- actions in our the activation of ordinary dislocation and superdislocation slip inside the c-lamellae and transfer of plastic

  17. Mechanical Signaling for Bone Modeling and Remodeling

    PubMed Central

    Robling, Alexander G.; Turner, Charles H.

    2012-01-01

    Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is great interest in elucidating how mechanical loading produces its observed effects, including increased bone formation, reduced bone loss, changes in bone cell differentiation and lifespan, among others. A molecular understanding of these processes is developing, and with it comes a profound new insight into the biology of bone. In this article, we review the nature of the physical stimulus to which bone cells mount an adaptive response, including the identity of the sensor cells, their attributes and physical environment, and putative mechanoreceptors they express. Particular attention is allotted to the focal adhesion and Wnt signaling, in light of their emerging role in bone mechanotransduction. The cellular mechanisms for increased bone loss during disuse, and reduced bone loss during loading are considered. Finally, we summarize the published data on bone cell accommodation, whereby bone cells stop responding to mechanical signaling events. Collectively, these data highlight the complex yet finely orchestrated process of mechanically regulated bone homeostasis. PMID:19817708

  18. Orientation of lamellar phases of lyotropic multicomponent mixtures, based on cetyltrimethylammonium bromide cationic detergent, in magnetic field

    NASA Astrophysics Data System (ADS)

    Kiirend, E. O.; Chumakova, S. P.; Pekhk, T. I.; Ivanov, N. R.

    2013-11-01

    The orientation of the lamellar phases in lyotropic systems based on cetyltrimethylammonium bromide (CTAB) detergent has been studied by polarization optical microscopy and 2H-NMR methods. The lamellar lyotropics studied are shown to align under a strong magnetic field of 11.7 T. According to 2H-NMR data, structural transformations of the lamellar phases may occur during orientation when the sample temperature increases.

  19. Vacuolar ATPase Regulates Surfactant Secretion in Rat Alveolar Type II Cells by Modulating Lamellar Body Calcium

    PubMed Central

    Chintagari, Narendranath Reddy; Mishra, Amarjit; Su, Lijing; Wang, Yang; Ayalew, Sahlu; Hartson, Steven D.; Liu, Lin

    2010-01-01

    Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase) dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1), an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca2+ chelator, BAPTA-AM, the protein kinase C (PKC) inhibitor, staurosporine, and the Ca2+/calmodulin-dependent protein kinase II (CaMKII), KN-62. Baf A1 induced Ca2+ release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca2+ pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca2+ mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion. PMID:20169059

  20. High-Temperature Sintering of Xenogeneic Bone Substitutes Leads to Increased Multinucleated Giant Cell Formation: In Vivo and Preliminary Clinical Results.

    PubMed

    Barbeck, Mike; Udeabor, Samuel; Lorenz, Jonas; Schlee, Markus; Holthaus, Marzellus Grosse; Raetscho, Nina; Choukroun, Joseph; Sader, Robert; Kirkpatrick, C James; Ghanaati, Shahram

    2015-10-01

    The present preclinical and clinical study assessed the inflammatory response to a high-temperature-treated xenogeneic material (Bego-Oss) and the effects of this material on the occurrence of multinucleated giant cells, implantation bed vascularization, and regenerative potential. After evaluation of the material characteristics via scanning electron microscopy, subcutaneous implantation in CD-1 mice was used to assess the inflammatory response to the material for up to 60 days. The clinical aspects of this study involved the use of human bone specimens 6 months after sinus augmentation. Established histologic and histomorphometric analysis methods were applied. After implantation, the material was well integrated into both species without any adverse reactions. Material-induced multinucleated giant cells were observed in both species and were associated with enhanced vascularization. These results revealed the high heat treatment led to an increase in the inflammatory tissue response to the biomaterial, and a combined increase in multinucleated giant cell formation. Further clarification of the differentiation of the multinucleated giant cells toward so-called osteoclast-like cells or foreign-body giant cells is needed to relate these cells to the physicochemical composition of the material. PMID:25105868

  1. Dynamics of edge dislocations in a sheared lamellar mesophase

    NASA Astrophysics Data System (ADS)

    Kumaran, V.

    2013-10-01

    The dynamics and interactions of edge dislocations in a nearly aligned sheared lamellar mesophase is analysed to provide insights into the relationship between disorder and rheology. First, the mesoscale permeation and momentum equations for the displacement field in the presence of external forces are derived from the model H equations for the concentration and momentum field. The secondary flow generated due to the mean shear around an isolated defect is calculated, and the excess viscosity due to the presence of the defect is determined from the excess energy dissipation due to the secondary flow. The excess viscosity for an isolated defect is found to increase with system size in the cross-stream direction as L3/2 for an isolated defect, though this divergence is cut-off due to interactions in a defect suspension. As the defects are sheared past each other due to the mean flow, the Peach-Koehler force due to elastic interaction between pairs of defects is found to cause no net displacement relative to each other as they approach from large separation to the distance of closest approach. The equivalent force due to viscous interactions is found to increase the separation for defects of opposite sign, and decrease the separation for defects of same sign. During defect interactions, we find that there is no buckling instability due to dilation of layers for systems of realistic size. However, there is another mechanism, which is the velocity difference generated across a slightly deformed bilayer due to the mean shear, which could result in the creation of new defects.

  2. Onlay Bone Grafts in Head and Neck Reconstruction

    PubMed Central

    Yazar, Sukru

    2010-01-01

    Bone grafts are used in a variety of clinical situations and can be divided into two categories: treatment of bone gaps (inlay bone grafting) and bone projection (onlay bone grafting). Cortical grafts are useful in situations requiring immediate mechanical strength. These grafts can survive with or without complete revascularization or resorption and are primarily used by plastic surgeons in the treatment of bone volume deficiency. Cancellous grafts, in contrast, have no mechanical strength and therefore require additional support to bridge bone defects. Thus, they are used primarily for the treatment of bone gaps and in general revascularize quickly, resorb completely, and stimulate significant new bone formation. PMID:22550447

  3. Bone Infections

    MedlinePLUS

    ... of the body, bones can get infected. The infections are usually bacterial, but can also be fungal. ... bloodstream. People who are at risk for bone infections include those with diabetes, poor circulation, or recent ...

  4. Bone tumor

    MedlinePLUS

    ... Bone metastases. In: Niederhuber JE, Armitage JO, Doroshow JH, et al., eds. Abeloff's Clinical Oncology . 5th ed. ... aggressive tumors of bone. In: Canale ST, Beaty JH, eds. Campbell's Operative Orthopaedics. Philadelphia, Pa: Elsevier Mosby; ...

  5. Bone Markers

    MedlinePLUS

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

  6. Quantification of Bone Growth Rate Variability in Rats Exposed to Micro- (near zero G) and Macrogravity (2G)

    NASA Technical Reports Server (NTRS)

    Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily

    1996-01-01

    Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

  7. Quantitation of Bone Growth Rate Variability in Rats Exposed to Micro-(near zero G) and Macrogravity (2G)

    NASA Technical Reports Server (NTRS)

    Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily

    1997-01-01

    Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro- (near zero G: e.g., Cosmos 1887 & 2044; SLS-1 & SLS-2) and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.

  8. Immunoregulation of bone remodelling

    PubMed Central

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  9. Wormian bones: a review.

    PubMed

    Bellary, Sharath S; Steinberg, Ashley; Mirzayan, Nadine; Shirak, Michelle; Tubbs, R Shane; Cohen-Gadol, Aaron A; Loukas, Marios

    2013-11-01

    Wormian bones are abnormal ossicles that develop from extra ossification centers within the cranium. They are most frequently located in the lambdoid suture or the coronal suture, and have been seen in the fontanelles, particularly the posterior fontanelle. It is unclear at this time exactly how or why they are formed, although genetic as well as environmental factors have been proposed. Their initial formation is thought to be caused by a degree of dural strain and increased sutural width. These conditions can result from mechanically induced stress due to intentional deformation like that practiced in ancient cultures, premature sutural closure, or from reduced skull ossification as seen in metabolic bone diseases. The cause of the malformation can have an influence on the number and location of Wormian bones. Clinically, Wormian bones are used as markers in the diagnoses of many autosomal dominant genetic disorders, namely, craniosynostosis and osteogenesis imperfecta. PMID:23959948

  10. High Heat Insulating Thermal Barrier Coating Designed with Large Two-Dimensional Inter-lamellar Pores

    NASA Astrophysics Data System (ADS)

    Liu, Tao; Zhang, Shan-Lin; Luo, Xiao-Tao; Yang, Guan-Jun; Li, Cheng-Xin; Li, Chang-Jiu

    2015-11-01

    Atmospheric plasma-sprayed ceramic coatings with a lamellar structure exhibit low thermal conductivity. However, high-temperature exposure causes sintering, which heals inter-lamellar two-dimensional (2D) pores and intra-splat pores. Such sintering effect increases the thermal conductivity of the coatings and consequently reduces the thermal insulation ability of TBCs. In this study, inter-lamellar 2D pores with a large opening width were introduced into the La2Zr2O7 (LZO) coating through the spraying of a LZO-SrO coating and the removal of the SrO splats in water. Then, the conventional LZO coating and the porous LZO coating were subjected to high-temperature exposure at 1300 °C, for different durations. It was found that the 2D pores resulting from SrO splats present little healing during high-temperature exposure, while the conventional 2D inter-lamellar pores with a small opening width heal rapidly. Thus, the thermal conductivity of the conventional LZO coating increased rapidly, while the unhealed 2D pores in the highly porous LZO coating contributed to the coating low thermal conductivity. The present results indicated that a high heat insulating thermal barrier coating with high stability can be fabricated though the introduction of inter-lamellar 2D pores with large opening width.

  11. Experiment K305: Quantitative analysis of selected bone parameters

    NASA Technical Reports Server (NTRS)

    Wrongski, T. J.; Morey-Holton, E.; Cann, C. E.; Arnaud, C. D.; Baylink, D. J.; Turner, R. T.; Jee, W. S. S.

    1981-01-01

    The skeletal alterations induced by space flight were determined to be a reduced rate of periosteal bone formation in tibial and humeral diaphyses, a decreased trabecular bone volume, and an increased fat content of the bone marrow in the proximal tibial metaphysis. An increased incidence of arrest lines in flight animals suggested that periosteal bone formation may have ceased during space flight. Endosteal bone resorption was not affected markedly.

  12. Remodeling of tissue-engineered bone structures in vivo

    PubMed Central

    Hofmann, Sandra; Hilbe, Monika; Fajardo, Robert J.; Hagenmüller, Henri; Nuss, Katja; Arras, Margarete; Müller, Ralph; von Rechenberg, Brigitte; Kaplan, David L.; Merkle, Hans P.; Meinel, Lorenz

    2013-01-01

    Implant design for bone regeneration is expected to be optimized when implant structures resemble the anatomical situation of the defect site. We tested the validity of this hypothesis by exploring the feasibility of generating different in vitro engineered bone-like structures originating from porous silk fibroin scaffolds decorated with RGD sequences (SF-RGD), seeded with human mesenchymal stem cells (hMSC). Scaffolds with small (106 – 212 ?m), medium (212 – 300 ?m) and large pore diameter ranges (300 – 425 ?m) were seeded with hMSC and subsequently differentiated in vitro into bone-like tissue resembling initial scaffold geometries and featuring bone-like structures. Eight weeks after implantation into calvarial defects in mice, the in vitro engineered bone-like tissues had remodeled into bone featuring different proportions of woven/lamellar bone bridging the defects. Regardless of pore diameter all implants integrated well, vascularization was advanced and, bone marrow ingrowth had started. Ultimately, in this defect model, the geometry of the in vitro generated tissue-engineered bone structure, trabecular- or plate-like, had no significant impact on the healing of the defect, owing to an efficient remodeling of its structure after implantation. PMID:23958323

  13. New laboratory tools in the assessment of bone quality.

    PubMed

    Chappard, D; Baslé, M F; Legrand, E; Audran, M

    2011-08-01

    Bone quality is a complex set of intricated and interdependent factors that influence bone strength. A number of methods have emerged to measure bone quality, taking into account the organic or the mineral phase of the bone matrix, in the laboratory. Bone quality is a complex set of different factors that are interdependent. The bone matrix organization can be described at five different levels of anatomical organization: nature (organic and mineral), texture (woven or lamellar), structure (osteons in the cortices and arch-like packets in trabecular bone), microarchitecture, and macroarchitecture. Any change in one of these levels can alter bone quality. An altered bone remodeling can affect bone quality by influencing one or more of these factors. We have reviewed here the main methods that can be used in the laboratory to explore bone quality on bone samples. Bone remodeling can be evaluated by histomorphometry; microarchitecture is explored in 2D on histological sections and in 3D by microCT or synchrotron. Microradiography and scanning electron microscopy in the backscattered electron mode can measure the mineral distribution; Raman and Fourier-transformed infra-red spectroscopy and imaging can simultaneously explore the organic and mineral phase of the matrix on multispectral images; scanning acoustic microscopy and nanoindentation provide biomechanical information on individual trabeculae. Finally, some histological methods (polarization, surface staining, fluorescence, osteocyte staining) may also be of interest in the understanding of quality as a component of bone fragility. A growing number of laboratory techniques are now available. Some of them have been described many years ago and can find a new youth; others having benefited from improvements in physical and computer techniques are now available. PMID:21347743

  14. Metallic Nanomaterials for Bone Tissue Engineering.

    PubMed

    Dhivya, S; Ajita, J; Selvamurugan, N

    2015-10-01

    Conventional grafting techniques for bone regeneration are currently being replaced by tissue engineering approaches of using 3D biomimetic materials. Of these biomaterials, metals have the highest mechanical strength; moreover, they play a major role in accelerating bone formation and promoting bone regeneration. They act as cofactors for enzymes, serving as a structural component of bone forming enzymes and proteins, stimulating angiogenesis, increasing extra-cellular matrix synthesis, promoting bone formation, and inhibiting bone resorption. Metals have the inherent ability to promote osseointegration and osteoconductivity and possess antimicrobial activity. The current developments in bone tissue engineering focus on metal surface modifications by physical and chemical treatments to improve their bioactivity. Based on the recent literature available, this review aims at discussing the biological role of metals, namely Zn, Ti, Zr, B, Sr, Mg, Ag, and Cu along with their surface modifications for significantly enhanced bone regeneration. PMID:26502634

  15. 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

  16. 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.

  17. Retraction of cold-drawn polyethylene - Influence of lamellar thickness and density.

    NASA Technical Reports Server (NTRS)

    Falender, J. R.; Hansen, D.

    1972-01-01

    The role of crystal morphology in the retraction of oriented linear polyethylene was studied utilizing samples crystallized under conditions controlled to vary, separately, lamellar crystal thickness and density. Samples were oriented in a simple shear deformation to a strain of 4.0 prior to measuring retraction tendency in creep- and relaxation-type tests. Characterizations of specimens were made using wide- and small-angle x-ray techniques. The specific morphological variations were chosen to test the hypothesis that a long-range elastic restoring force can originate in conjunction with deformation of lamellar crystals and the consequent increase in lamellar crystal surface area and surface free energy. The results support this hypothesis.

  18. Lamellar-twisting-induced circular dichroism of chromophore moieties in banded spherulites with evolution of homochirality.

    PubMed

    Li, Ming-Chia; Wang, Hsiao-Fang; Chiang, Chen-Hung; Lee, Yu-Der; Ho, Rong-Ming

    2014-04-22

    Banded spherulites are formed by crystallization of a chiral polymer that is end-capped with chromophore. Induced circular dichroism (ICD) of the chromophore can be found in the crystallized chiral polymers, giving exclusive optical response of the ICD. The ICD signals are presumed to be driven by the lamellar twisting in the crystalline spherulites, and the exclusive optical activity is attributed to the chirality transfer from molecular level to macroscopic level. To verify the suggested mechanism, the sense of the lamellar twisting in the crystalline spherulite is determined using PLM for the comparison with the ICD signals of the chromophore in the electron circular dichroism spectrum. The conformational chirality of the chiral polymer is determined by the vibrational circular dichroism spectrum. On the basis of the chiroptical results, evolution of homochirality from helical polymer chains (conformational chirality) to lamellar twisting in the banded spherulite (hierachical chirality) is suggested. PMID:24644091

  19. Lyotropic La-containing lamellar liquid crystals: phase behaviour, thermal and structural properties.

    PubMed

    Selivanova, N M; Konov, A B; Romanova, K A; Gubaidullin, A T; Galyametdinov, Yu G

    2015-10-21

    This paper provides the results of POM, DSC and XRPD methods characterizing the liquid crystalline behaviour, thermal properties and structural parameters of lyotropic systems based on a nonionic surfactant and lanthanum nitrate (La(3+)). The systems based on tetraethylene glycol monododecyl ether (C12EO4) and lanthanum nitrate have been demonstrated to form a lamellar phase. The concentration and temperature ranges of the existence of mesophases as well as thermodynamic parameters of phase transitions have been estimated. The structural parameters of the lamellar phase of the C12EO4/La(3+)/water systems have been determined using X-ray diffraction. The model of molecular packing in lamellar lanthanide-containing lyotropic mesophases was proposed for the observed patterns of structural parameters obtained at various water contents. NMR (1)H with a pulsed magnetic field gradient has been used to characterize molecular motions in the C12EO4/La(3+)/H2O systems with different water contents. PMID:26314681

  20. High-temperature deformation of uniaxially aligned lamellar TiAl/Ti{sub 3}Al

    SciTech Connect

    Heinrich, H.; Abaecherli, V.; Wilkins, D.J.; Kostorz, G.

    1999-07-01

    Uniaxially aligned polysynthetically twinned two-phase TiAl/Ti{sub 3}Al material is produced by induction zone melting and deformed in uniaxial compression. Above 1,000 K the strain rate sensitivity is independent of the lamellar orientation and increases strongly with increasing deformation temperature. Results for the strain rate sensitivity parameters are somewhat lower than those obtained for {gamma}-TiAl single- and polycrystals. If the lamellae are oriented parallel or perpendicular to the deformation axis, the flow stress decreases with increasing strain. After plastic deformation the dislocation density in the lamellae is remarkably low indicating recovery processes. At the lamellar interfaces misfit dislocations and periodic arrangements of dislocations with Burgers vectors inclined to the lamellar boundaries are found. In contrast to deformation at lower temperatures, deformation twinning is rare.

  1. Strengthening behavior of beta phase in lamellar microstructure of TiAl alloys

    NASA Astrophysics Data System (ADS)

    Zhu, Hanliang; Seo, D. Y.; Maruyama, K.

    2010-01-01

    ? phase can be introduced to TiAl alloys by the additions of ? stabilizing elements such as Cr, Nb, W, and Mo. The ? phase has a body-centered cubic lattice structure and is softer than the ?2 and ? phases in TiAl alloys at elevated temperatures, and hence is thought to have a detrimental effect on creep strength. However, fine ? precipitates can be formed at lamellar interfaces by proper heat treatment conditions and the ? interfacial precipitate improves the creep resistance of fully lamellar TiAl alloys, since the phase interface of ?/? retards the motion of dislocations during creep. This paper reviews recent research on high-temperature strengthening behavior of the ? phase in fully lamellar TiAl alloys.

  2. Identification of O-Linked N-Acetylglucosamine (O-GlcNAc)-modified Osteoblast Proteins by Electron Transfer Dissociation Tandem Mass Spectrometry Reveals Proteins Critical for Bone Formation*

    PubMed Central

    Nagel, Alexis K.; Schilling, Michael; Comte-Walters, Susana; Berkaw, Mary N.; Ball, Lauren E.

    2013-01-01

    The nutrient-responsive ?-O-linked N-acetylglucosamine (O-GlcNAc) modification of critical effector proteins modulates signaling and transcriptional pathways contributing to cellular development and survival. An elevation in global protein O-GlcNAc modification occurs during the early stages of osteoblast differentiation and correlates with enhanced transcriptional activity of RUNX2, a key regulator of osteogenesis. To identify other substrates of O-GlcNAc transferase in differentiating MC3T3E1 osteoblasts, O-GlcNAc-modified peptides were enriched by wheat germ agglutinin lectin weak affinity chromatography and identified by tandem mass spectrometry using electron transfer dissociation. This peptide fragmentation approach leaves the labile O-linkage intact permitting direct identification of O-GlcNAc-modified peptides. O-GlcNAc modification was observed on enzymes involved in post-translational regulation, including MAST4 and WNK1 kinases, a ubiquitin-associated protein (UBAP2l), and the histone acetyltransferase CREB-binding protein. CREB-binding protein, a transcriptional co-activator that associates with CREB and RUNX2, is O-GlcNAcylated at Ser-147 and Ser-2360, the latter of which is a known site of phosphorylation. Additionally, O-GlcNAcylation of components of the TGF?-activated kinase 1 (TAK1) signaling complex, TAB1 and TAB2, occurred in close proximity to known sites of Ser/Thr phosphorylation and a putative nuclear localization sequence within TAB2. These findings demonstrate the presence of O-GlcNAc modification on proteins critical to bone formation, remodeling, and fracture healing and will enable evaluation of this modification on protein function and regulation. PMID:23443134

  3. [Newly developed drugs to improve bone strength].

    PubMed

    Hagino, Hiroshi

    2016-01-01

    Drugs for the treatment of osteoporosis improve bone strength by inhibiting bone resorption or stimulating bone formation. New drugs already using some action mechanism such as bisphosphonate or parathyroid hormone-related peptide analog are being developed in Japan. In addition, new drugs with new action mechanisms such as cathepsin K inhibitor or anti-sclerostin antibody are also being developed and it has been reported that they have good potential to increase bone mineral density. PMID:26728536

  4. Radiology of bone diseases. 5th edition

    SciTech Connect

    Greenfield, G.

    1990-01-01

    This book reports on anatomy, physiology, and biochemistry of bone. This book presents alterations in overall characteristics such as density and bone texture. It describes Salterations in specific anatomic regions of bone, as well ad discuss solitary bone lesions. The style in which the diseases are grouped according to specific regions and morphologic alterations rather than by individual pathologic condition is the most powerful aspect of this format.

  5. 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.

  6. Skeletal remodelling and bone related hormones in two adults with increased bone mass.

    PubMed

    Manzke, E; Gruber, H E; Hiness, R W; Baylink, D J

    1982-01-01

    This study of two cases documents increased bone mass in a 30-yr old man and osteopetrosis in a 38-yr-old woman and examines the patients in terms of radiologic features, bone photon absorptiometry and bo