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1

Peripheral Leptin Regulates Bone Formation  

PubMed Central

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

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

2012-01-01

2

Dilatational band formation in bone  

PubMed Central

Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone’s nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC?/?, OPN?/?, OC-OPN?/?;?/?) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone. PMID:23129653

Poundarik, Atharva A.; Diab, Tamim; Sroga, Grazyna E.; Ural, Ani; Boskey, Adele L.; Gundberg, Caren M.; Vashishth, Deepak

2012-01-01

3

Evidence for arrested bone formation during spaceflight  

NASA Technical Reports Server (NTRS)

Addressing the question of whether the bone formed in space is unusual, the morphology of bone made at the tibial diaphysis of rats before, during, and after spaceflight is studied. Evidence of arrest lines in the bone formed in space is reported suggesting that bone formation ceases along portions of the periosteum during spaceflight. Visualized by microradiography, the arrest lines are shown to be less mineralized than the surrounding bone matrix. When viewed by scanning electron microscopy, it is seen that bone fractures more readily at the site of an arrest line. These observations are seen as suggesting that arrest lines are a zone of weakness and that their formation may result in decreased bone strength in spite of normalization of bone formation after flight. The occurrence, location, and morphology of arrest lines are seen as suggesting that they are a visible result of the phenomenon of arrested bone formation.

Turner, R. T.; Bobyn, J. D.; Duvall, P.; Morey, E. R.; Baylink, D. J.; Spector, M.

1982-01-01

4

Inhibition of bone formation during space flight  

NASA Technical Reports Server (NTRS)

Parameters of bone formation and resorption were measured in rats orbited for 19.5 days aboard the Soviet Cosmos 782 biological satellite. The most striking effects were on bone formation. During flight, rats formed significantly less periosteal bone than did control rats on the ground. An arrest line at both the periosteum and the endosteum of flight animals suggests that a complete cecessation of bone growth occurred. During a 26-day postflight period, the defect in bone formation was corrected. No significant changes in bone resorption were observed.

Morey, E. R.; Baylink, D. J.

1978-01-01

5

Shell Formation and Bone Strength Laying Hens  

E-print Network

Shell Formation and Bone Strength in Laying Hens Effects of Age, Daidzein and Exogenous Estrogen Cover aquarelle: E. Spörndly-Nees #12;Shell Formation and Bone Strength in Laying Hens Effects of Age as well as an economical problem. Parallel with reduced shell quality the bone strength declines

6

Recombinant Human Bone Morphogenetic Protein Induces Bone Formation  

Microsoft Academic Search

We 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 mug of partially purified recombinant human BMP-2A resulted in cartilage by day

Elizabeth A. Wang; Vicki Rosen; Josephine S. D'Alessandro; Marc Bauduy; Paul Cordes; Tomoko Harada; David I. Israel; Rodney M. Hewick; Kelvin M. Kerns; Peter Lapan; Deborah H. Luxenberg; David McQuid; Ioannis K. Moutsatsos; John Nove; John M. Wozney

1990-01-01

7

Space flight and bone formation  

NASA Technical Reports Server (NTRS)

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.

Doty, St B.

2004-01-01

8

Early radiographic changes in radiation bone injury  

SciTech Connect

A chronologic series of periapical radiographs was evaluated for the purpose of detecting damage to bone and tooth-supporting tissues in a patient receiving radiation therapy for a basal cell carcinoma of the mandibular gingiva. Widening of the periodontal space was one of the early radiographic changes observed. It is suggested, from the sequence of radiographic changes, that radiation-induced changed in the circulatory system of the bone might be primarily responsible for the resulting changes.

Fujita, M.; Tanimoto, K.; Wada, T.

1986-06-01

9

The effects of early postoperative radiation on vascularized bone grafts  

SciTech Connect

The effects of early postoperative radiation were assessed in free nonvascularized and free vascularized rib grafts in the canine model. The mandibles of one-half of the dogs were exposed to a cobalt 60 radiation dose of 4080 cGy over a 4-week period, starting 2 weeks postoperatively. The patency of vascularized grafts was confirmed with bone scintigraphy. Histological studies, including ultraviolet microscopy with trifluorochrome labeling, and histomorphometric analyses were performed. Osteocytes persist within the cortex of the vascularized nonradiated grafts to a much greater extent than in nonvascularized, nonradiated grafts. Cortical osteocytes do not persist in either vascularized or nonvascularized grafts subjected to radiation. New bone formation is significantly retarded in radiated grafts compared with nonradiated grafts. Periosteum and endosteum remained viable in the radiated vascularized grafts, producing both bone union and increased bone turnover, neither of which were evident to any significant extent in nonvascularized grafts. Bone union was achieved in vascularized and non-vascularized nonradiated bone. In the radiated group of dogs, union was only seen in the vascularized bone grafts.

Evans, H.B.; Brown, S.; Hurst, L.N. (Division of Plastic and Reconstructive Surgery, University of Western Ontario, London (Canada))

1991-06-01

10

MicroRNAs involved in bone formation.  

PubMed

During skeletal development, mesenchymal progenitor cells undergo a multistage differentiation process in which they proliferate and become bone- and cartilage-forming cells. This process is tightly regulated by multiple levels of regulatory systems. The small non-coding RNAs, microRNAs (miRNAs), post-transcriptionally regulate gene expression. Recent studies have demonstrated that miRNAs play significant roles in all stages of bone formation, suggesting the possibility that miRNAs can be novel therapeutic targets for skeletal diseases. Here, we review the role and mechanism of action of miRNAs in bone formation. We discuss roles of specific miRNAs in major types of bone cells, osteoblasts, chondrocytes, osteoclasts, and their progenitors. Except a few, the current knowledge about miRNAs in bone formation has been obtained mainly by in vitro studies; further validation of these findings in vivo is awaited. We also discuss about several miRNAs of particular interest in the light of future therapies of bone diseases. PMID:25108446

Papaioannou, Garyfallia; Mirzamohammadi, Fatemeh; Kobayashi, Tatsuya

2014-12-01

11

[BMP signaling and bone formation].  

PubMed

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

Katagiri, Takenobu

2012-11-01

12

Novel Regulators of Bone Formation: Molecular Clones and Activities  

Microsoft Academic Search

Protein extracts derived from bone can initiate the process that begins with cartilage formation and ends in de novo bone formation. The critical components of this extract, termed bone morphogenetic protein (BMP), that direct cartilage and bone formation as well as the constitutive elements supplied by the animal during this process have long remained unclear. Amino acid sequence has been

John M. Wozney; Vicki Rosen; Anthony J. Celeste; Lisa M. Mitsock; Matthew J. Whitters; Ronald W. Kriz; Rodney M. Hewick; Elizabeth A. Wang

1988-01-01

13

Increased bone formation in osteocalcin-deficient mice  

Microsoft Academic Search

VERTEBRATES constantly remodel bone. The resorption of preexisting bone by osteoclasts and the formation of new bone by osteoblasts is strictly coordinated to maintain bone mass within defined limits. A few molecular determinants of bone remodelling that affect osteoclast activity1-3 have been characterized, but the molecular determinants of osteoblast activity are unknown. To investigate the role of osteocalcin, the most

Patricia Ducy; Christelle Desbois; Brendan Boyce; Gerald Pinero; Beryl Story; Colin Dunstan; Erica Smith; Jeffrey Bonadio; Steven Goldstein; Caren Gundberg; Allan Bradley; Gerard Karsenty

1996-01-01

14

Erythropoietin Couples Hematopoiesis with Bone Formation  

PubMed Central

Background It is well established that bleeding activates the hematopoietic system to regenerate the loss of mature blood elements. We have shown that hematopoietic stem cells (HSCs) isolated from animals challenged with an acute bleed regulate osteoblast differentiation from marrow stromal cells. This suggests that HSCs participate in bone formation where the molecular basis for this activity is the production of BMP2 and BMP6 by HSCs. Yet, what stimulates HSCs to produce BMPs is unclear. Methodology/Principal Findings In this study, we demonstrate that erythropoietin (Epo) activates Jak-Stat signaling pathways in HSCs which leads to the production of BMPs. Critically, Epo also directly activates mesenchymal cells to form osteoblasts in vitro, which in vivo leads to bone formation. Importantly, Epo first activates osteoclastogenesis which is later followed by osteoblastogenesis that is induced by either Epo directly or the expression of BMPs by HSCs to form bone. Conclusions/Significance These data for the first time demonstrate that Epo regulates the formation of bone by both direct and indirect pathways, and further demonstrates the exquisite coupling between hematopoesis and osteopoiesis in the marrow. PMID:20523730

Ziegler, Anne M.; Pedersen, Elisabeth A.; Wang, Jianhua; Wang, Zhuo; Song, Junhui; Wang, Jingcheng; Lee, Clara H.; Sud, Sudha; Pienta, Kenneth J.; Krebsbach, Paul H.; Taichman, Russell S.

2010-01-01

15

Experimental adipocere formation: implications for adipocere formation on buried bone.  

PubMed

Adipocere, or grave wax (adipo = fat, cere = wax), is a distinctive decomposition product composed primarily of fatty acids (FA) and their alkali salts. FA result from the bacterial enzymatic hydrolysis of body fats. Reactions with ammonia and alkali metals originating from body fluids and pore waters of the depositional environment produce alkali salts of FA (soap). Adipocere formation is generally associated with burial of corpses with ample adipose tissue available. No indications that adipocere can form on defleshed remains have been presented in the literature. At the termination of a long-term bone diagenesis experiment, several samples were found to possess growths of an unknown compound. Gas chromatography-mass spectrometry confirmed that the growths are adipocere. The results herein reveal that adipocere can indeed form on defleshed bones under the right conditions and that even residual adipose and lipids in defleshed bones are sufficient to produce adipocere growth on the surfaces of bone. PMID:22211839

Moses, Randolph J

2012-05-01

16

The Relation between Bone and Stone Formation  

PubMed Central

Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total body calcium. The source of this additional urine calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD) which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover, as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of hypercalciuria on bone we utilized our genetic hypercalciuric stone-forming (GHS) rats which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls and all the GHS rats form kidney stones while control rats do not. The hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and their bones are more fracture prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of hypercalciuria and stone formation in humans to ultimately improve bone health of patients with kidney stones. PMID:23247537

Krieger, Nancy S.; Bushinsky, David A.

2012-01-01

17

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

SciTech Connect

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.

Goodman, W.G.

1984-05-01

18

Regulation of bone resorption and formation by purines and pyrimidines  

E-print Network

Regulation of bone resorption and formation by purines and pyrimidines Astrid Hoebertz1 , Timothy R, signalling through P2 receptors, might play important roles in the regulation of bone and cartilage cells Osteoblasts (bone-forming cells) Osteoclasts (bone-resorbing cells) Origin Derived from precursors

Burnstock, Geoffrey

19

Early periosteal changes in translation-induced bone modelling.  

PubMed Central

This primarily ultrastructural study examines the effects of strain induced in the periosteum using an in vivo translation model with minimal internal bone strain. Caudal vertebrae (CV 7, 8, 9) from 4 d rats were threaded onto the arms of prestressed helical torsion springs and transplanted subcutaneously into 50 g hosts of the same inbred strain. After 7 d the appliances were activated in the experimental rats causing the bones to translate, i.e. to move through the soft tissues. Tissues for histology were obtained at this time (0) and at 1, 3, 5, 7, 10 and 14 d; for electron microscopy, experimental tissues were obtained at 0 time, 30 min, 1, 2, 6, 12, 18 and 24 h and at 0 time and 12 h for the controls. As the arms of the appliance move apart, traction on the enveloping soft tissues produces compression of the periosteum on the leading side and tension on the trailing side with resultant eccentric remodelling of the bones, generally opposite to the direction of movement. A rapid and differential structural response occurs, characterised by accelerated formation on the trailing side with the reverse on the leading, where changes are not as marked initially. Long thin trabeculae oriented in the line of tension form on the trailing side whereas the shaft on the leading side becomes thinner and flatter. Ultrastructural examination of the early stages shows that the fibrous periosteum is first affected, with alterations in collagen packing preceding cellular changes. The midzone shows the greatest change and events here presage those which finally occur at the bone surface and are reflected in altered osteoblastic activity. This study shows that translation-induced stress produces rapid morphological changes in the periosteum which, by acting as an integrated unit, has the capacity to modulate the adaptive bone modelling response. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:8226294

Feik, S A

1993-01-01

20

Silicon: A requirement in bone formation independent of vitamin D 1  

Microsoft Academic Search

Summary  Silicon has been reported to be involved in an early stage of bone formation as a result of earlier in vitro and in vivo studies\\u000a in this laboratory. It is now possible to demonstrate that silicon exerts an effect on bone formation independent of the action\\u000a of vitamin D. Day-old cockerels were fed Sideficient and Si-supplemented diets with adequate and

Edith M. Carlisle

1981-01-01

21

Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats  

Microsoft Academic Search

Cells from fetal or neonatal skeleton can synthesize bone-like tissue in vitro. In contrast, formation of bone-like tissue in vitro by cells derived from adult animals has rarely been reported and has not been achieved using cells from bone marrow. We have explored development of bone-like tissue in vitro by bone marrow stromal cells. Marrow stromal cells obtained from 40–43-day-old

C. Maniatopoulos; J. Sodek; A. H. Melcher

1988-01-01

22

Bone Balance within a Cortical BMU: Local Controls of Bone Resorption and Formation  

PubMed Central

Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors. PMID:22844401

Smith, David W.; Gardiner, Bruce S.; Dunstan, Colin

2012-01-01

23

The impact of skeletal unloading on bone formation  

NASA Technical Reports Server (NTRS)

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.

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

2003-01-01

24

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

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

25

In Vitro and In Vivo effects of ipriflavone on bone formation and bone biomechanics  

Microsoft Academic Search

Ipriflavone (IP) positively affects bone density in postmenopausal osteoporosis, primarily by inhibiting bone resorption.\\u000a Using in vitro models of human osteoblast differentiation, we have observed that IP and some of its metabolites stimulate the expression\\u000a of bone sialoprotein, decorin, and type I collagen, and facilitate the deposition of mineralized matrix. This suggests that\\u000a IP may stimulate bone formation in addition

R. Civitelli

1997-01-01

26

Differential Gene Expression from Microarray Analysis Distinguishes Woven and Lamellar Bone Formation in the Rat Ulna following Mechanical Loading  

PubMed Central

Formation of woven and lamellar bone in the adult skeleton can be induced through mechanical loading. Although much is known about the morphological appearance and structural properties of the newly formed bone, the molecular responses to loading are still not well understood. The objective of our study was to use a microarray to distinguish the molecular responses between woven and lamellar bone formation induced through mechanical loading. Rat forelimb loading was completed in a single bout to induce the formation of woven bone (WBF loading) or lamellar bone (LBF loading). A set of normal (non-loaded) rats were used as controls. Microarrays were performed at three timepoints after loading: 1 hr, 1 day and 3 days. Confirmation of microarray results was done for a select group of genes using quantitative real-time PCR (qRT-PCR). The micorarray identified numerous genes and pathways that were differentially regulated for woven, but not lamellar bone formation. Few changes in gene expression were evident comparing lamellar bone formation to normal controls. A total of 395 genes were differentially expressed between formation of woven and lamellar bone 1 hr after loading, while 5883 and 5974 genes were differentially expressed on days 1 and 3, respectively. Results suggest that not only are the levels of expression different for each type of bone formation, but that distinct pathways are activated only for woven bone formation. A strong early inflammatory response preceded an increase in angiogenic and osteogenic gene expression for woven bone formation. Furthermore, at later timepoints there was evidence of bone resorption after WBF loading. In summary, the vast coverage of the microarray offers a comprehensive characterization of the early differences in expression between woven and lamellar bone formation. PMID:22216249

McKenzie, Jennifer A.; Bixby, Elise C.; Silva, Matthew J.

2011-01-01

27

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

Microsoft Academic Search

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

Seth W. Donahue; Michael R. Vaughan; Laurence M. Demers; Henry J. Donahue

2003-01-01

28

Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.  

PubMed

Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover. PMID:24126694

Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

2014-09-01

29

Increased production of IL-7 uncouples bone formation from bone resorption during estrogen deficiency  

PubMed Central

Postmenopausal bone loss stems from the inability of osteoblastic activity to match the increase in osteoclastic bone resorption induced by estrogen deficiency. However, the mechanism that uncouples osteoblast from osteoclast activities remains unexplained. We show that ovariectomy enhances the production of the osteoclastogenic cytokine IL-7, and that its neutralization in vivo prevents ovariectomy-induced bone loss. Surprisingly, serum osteocalcin levels, a biochemical marker of bone formation, suggested that the bone-sparing effects of IL-7 neutralization were due not only to inhibition of bone resorption, but also to stimulation of bone formation. Consistent with these data, addition of IL-7 to neonatal calvarial organ cultures blocked new bone formation, and injection of IL-7 into mice in vivo inhibited bone formation as measured by calcein incorporation into long bones. The antianabolic effects of IL-7 were consistent with an observed downregulation of the osteoblast-specific transcription factor core-binding factor ?1/Runx2. Thus, because it targets both the osteoclast and the osteoblast pathways, IL-7 is central to the altered bone turnover characteristic of estrogen deficiency. PMID:12464669

Weitzmann, M. Neale; Roggia, Cristiana; Toraldo, Gianluca; Weitzmann, Louise; Pacifici, Roberto

2002-01-01

30

Leptin regulates bone formation via the sympathetic nervous system  

NASA Technical Reports Server (NTRS)

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.

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

2002-01-01

31

Early Formation of Terrestrial Crust  

NASA Astrophysics Data System (ADS)

Early (?4.5 Ga) Formation of Terrestrial Crust T.M. Harrison1, A.K. Schmitt1, M.T. McCulloch2, and O.M. Lovera1 1Department of Earth and Space Sciences and IGPP, UCLA, Los Angeles, CA 90095, USA; 2Research School of Earth Sciences, Australian National University, Canberra, A.C.T. 2601 AUSTRALIA Large deviations in ?repsilonHf(T) from bulk silicate Earth seen in >4 Ga detrital zircons from Jack Hills, Western Australia, have been interpreted as reflecting a major differentiation of the silicate Earth at ca. 4.4 to 4.5 Ga. We have expanded the characterization of 176Hf/177Hf (Hf) in Hadean zircons by acquiring a further 116 laser ablation Lu-Hf measurements on 87 grains with ion microprobe 207Pb/206Pb ages up to 4.36 Ga. Most measurements employed concurrent Lu-Hf and 207Pb/206Pb analyses, permitting assessment of the use of ion microprobe data to characterize the age of the volumetrically larger domain sampled by laser drilling. Our new results confirm and extend the earlier observation of significant negative deviations in ?repsilonHf(T) throughout the Hadean, although no positive ?repsilonHf(T) values were documented in this study. These data yields an essentially uniform spectrum of single-stage model ages between 4.54 and 4.20 Ga for extraction of the zircons' protoliths from a chondritic reservoir. We derived the full error propagation expression for a parameter, ?repsilono, which measures the difference of a sample from solar system initial (Hf) (Hfo), and from this conclude that data plotting close to (Hfo), are statistically meaningful and consistent with silicate differentiation at 4.540±0.006 Ga. ?18O and Ti thermometry for these Hadean zircons show little obvious correlation with initial (Hf), consistent with their derivation through fusion of a broad suite of crustal rock types under near water-saturated conditions. Together with the inclusion assemblage and other isotopic and trace element data obtained from these ancient zircons, our results indicate essentially continuous derivation of crust from the mantle from 4.5 to 4.2 Ga, concurrent with recycling into the mantle and internal crustal re-working. These results represent further evidence that by 4.35 Ga, portions of the crust had taken on continental characteristics.

Harrison, T. M.; Schmitt, A. K.; McCulloch, M. T.; Lovera, O. M.

2007-12-01

32

Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis  

PubMed Central

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (?/?) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP?/? mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (?12 mo) BSP?/? mice. At 4 mo, BSP?/? mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP?/? versus WT bone marrow stromal cultures. BSP?/? hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP?/? mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN?/? mice. PMID:18458111

Malaval, Luc; Wade-Guéye, Ndéyé Marième; Boudiffa, Maya; Fei, Jia; Zirngibl, Ralph; Chen, Frieda; Laroche, Norbert; Roux, Jean-Paul; Burt-Pichat, Brigitte; Duboeuf, François; Boivin, Georges; Jurdic, Pierre; Lafage-Proust, Marie-Hélène; Amédée, Joëlle; Vico, Laurence; Rossant, Janet; Aubin, Jane E.

2008-01-01

33

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

SciTech Connect

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.

Nurmio, Mirja, E-mail: Mirja.Nurmio@utu.fi [Department of Physiology, University of Turku (Finland); Department of Pediatrics, University of Turku (Finland); Joki, Henna, E-mail: Henna.Joki@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Kallio, Jenny, E-mail: Jenny.Kallio@utu.fi [Department of Physiology, University of Turku (Finland); Maeaettae, Jorma A., E-mail: jorma.maatta@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Department of Turku Center for Disease Modeling, University of Turku (Finland); Vaeaenaenen, H. Kalervo, E-mail: kalervo.vaananen@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland); Toppari, Jorma, E-mail: Jorma.Toppari@utu.fi [Department of Physiology, University of Turku (Finland); Department of Pediatrics, University of Turku (Finland); Jahnukainen, Kirsi, E-mail: Kirsi.Jahnukainen@utu.fi [Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institutet and University Hospital, Stockholm (Sweden); Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki (Finland); Laitala-Leinonen, Tiina, E-mail: tilale@utu.fi [Department of Cell Biology and Anatomy, University of Turku (Finland)

2011-08-01

34

Polymer-ceramic composite that mimics bone formation  

NASA Astrophysics Data System (ADS)

Research was done on a biomimetic building material with the unique properties of bone. Bone, as well as other natural materials such as shell, obtains its toughness and strength as a result of utilizing optimum materials, structural form and carefully controlling the process of bone formation. The organic fibers are made first and the matrix grown around them as opposed to conventional ceramics in which any fibers are added to the matrix. The research presented focuses on creating a polymer/cement composite which mimics bone by controlling the chemical makeup and sequencing of fabrication. The rules under which bone material naturally forms, albeit at a macroscale, are followed in order to match the intimate connection between material phases of bone. The research presented here uses cement and condensation polymers. The proposed design more carefully controls the formation process by utilizing the symbiotic relationship of the two material formation reactions. The inorganic phase formation is initiated and controlled by the organic phase formation as occurs in bone formation. Like bone this new material offers great opportunity for improved mechanical and chemical bonding.

Dry, Carolyn M.

1999-05-01

35

Impaired Bone Formation in Pdia3 Deficient Mice  

PubMed Central

1?,25-dihydroxyvitamin D3 [1?,25(OH)2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3) mediates 1?,25(OH)2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/? heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/? mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/? mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/? mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/? heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1?,25(OH)2D3’s actions in regulating skeletal development. PMID:25405762

Wang, Yun; Nizkorodov, Alexandr; Riemenschneider, Kelsie; Lee, Christopher S. D.; Olivares-Navarrete, Rene; Schwartz, Zvi; Boyan, Barbara D.

2014-01-01

36

Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo  

PubMed Central

Amylin is a member of the calcitonin family of hormones cosecreted with insulin by pancreatic ? cells. Cell culture assays suggest that amylin could affect bone formation and bone resorption, this latter function after its binding to the calcitonin receptor (CALCR). Here we show that Amylin inactivation leads to a low bone mass due to an increase in bone resorption, whereas bone formation is unaffected. In vitro, amylin inhibits fusion of mononucleated osteoclast precursors into multinucleated osteoclasts in an ERK1/2-dependent manner. Although Amylin +/? mice like Amylin-deficient mice display a low bone mass phenotype and increased bone resorption, Calcr +/? mice display a high bone mass due to an increase in bone formation. Moreover, compound heterozygote mice for Calcr and Amylin inactivation displayed bone abnormalities observed in both Calcr +/? and Amylin +/? mice, thereby ruling out that amylin uses CALCR to inhibit osteoclastogenesis in vivo. Thus, amylin is a physiological regulator of bone resorption that acts through an unidentified receptor. PMID:14970190

Dacquin, Romain; Davey, Rachel A.; Laplace, Catherine; Levasseur, Regis; Morris, Howard A.; Goldring, Steven R.; Gebre-Medhin, Samuel; Galson, Deborah L.; Zajac, Jeffrey D.; Karsenty, Gerard

2004-01-01

37

Regulation of bone morphogenetic proteins in early embryonic development  

NASA Astrophysics Data System (ADS)

Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-? family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

Yamamoto, Yukiyo; Oelgeschläger, Michael

2004-11-01

38

Early chronic kidney disease-mineral bone disorder stimulates vascular calcification  

PubMed Central

The chronic kidney disease-mineral and bone disorder (CKD-MBD) syndrome is an extremely important complication of kidney diseases. Here we tested whether CKD-MBD causes vascular calcification in early kidney failure by developing a mouse model of early CKD in a background of atherosclerosis stimulated arterial calcification. CKD equivalent in glomerular filtration reduction to human CKD stage 2 stimulated early vascular calcification and inhibited the tissue expression of ?-klotho (klotho) in the aorta. In addition, osteoblast transition in the aorta was stimulated by early CKD as shown by the expression of the critical transcription factor, RUNX2. The ligand associated with the klotho-fibroblast growth factor receptor complex, FGF23, was found to be expressed in the vascular media of sham operated mice. Its expression was decreased in early CKD. Increased circulating levels of the osteocyte secreted proteins, FGF23, and sclerostin may have been related to increased circulating klotho levels. Finally, we observed low turnover bone disease with a reduction in bone formation rates more than bone resorption. Thus, the CKD-MBD, characterized by cardiovascular risk factors, vascular calcification, increased circulating klotho, FGF23 and sclerostin levels, and low turnover renal osteodystrophy, was established in early CKD. Early CKD caused a reduction of vascular klotho, stimulated vascular osteoblastic transition, increased osteocytic secreted proteins, and inhibited skeletal modeling producing the CKD-MBD. PMID:23884339

Fang, Yifu; Ginsberg, Charles; Sugatani, Toshifumi; Monier-Faugere, Marie-Claude; Malluche, Hartmut; Hruska, Keith A

2013-01-01

39

Osteopenia and decreased bone formation in osteonectin-deficient mice  

PubMed Central

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

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

2000-01-01

40

Controlled Delivery of Zoledronate Improved Bone Formation Locally In Vivo  

PubMed Central

Bisphosphonates (BPs) have been widely used in clinical treatment of bone diseases with increased bone resorption because of their strong affinity for bone and their inhibition of bone resorption. Recently, there has been growing interest in their improvement of bone formation. However, the effect of local controlled delivery of BPs is unclear. We used polylactide acid-glycolic acid copolymer (PLGA) as a drug carrier to deliver various doses of the bisphosphonate zoledronate (Zol) into the distal femur of 8-week-old Sprague-Dawley rats. After 6 weeks, samples were harvested and analyzed by micro-CT and histology. The average bone mineral density and mineralized bone volume fraction were higher with medium- and high-dose PLGA-Zol (30 and 300 µg Zol, respectively) than control and low-dose Zol (3 µg PLGA-Zol; p<0.05). Local controlled delivery of Zol decreased the numbers of osteoclast and increased the numbers of osteoblast. Moreover, local controlled delivery of medium- and high-dose Zol accelerated the expression of bone-formation markers. PLGA used as a drug carrier for controlled delivery of Zol may promote local bone formation. PMID:24618585

Peng, Jiang; Lu, Qiang; Wang, Yu; Wang, Aiyuan; Guo, Quanyi; Gao, Xupeng; Xu, Wenjing; Lu, Shibi

2014-01-01

41

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys  

NASA Technical Reports Server (NTRS)

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.

Cann, Christopher; Young, Donald R.

1976-01-01

42

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

PubMed

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

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

2012-06-01

43

Early Formative Evaluation of Educational Television  

Microsoft Academic Search

This article examines the incorporation of formative evaluation in the early stages of ETV programme development, and argues that Self?Formative Evaluation, an evaluation system conducted by the developers of an ETV programme and in?house evaluators, should be conducted. A list of criteria that can be used in this evaluation process is given

A. Duby

1988-01-01

44

Premature loss of bone remodeling compartment canopies is associated with deficient bone formation: a study of healthy individuals and patients with Cushing's syndrome.  

PubMed

A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling were proposed to be critical players in this mechanism. Here, we provide support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces. Both cohorts showed almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above bone forming surfaces. This indicates that BRC canopies are invariably associated with the early stage of the remodeling cycle, but may disappear later. Interestingly, in control and two-thirds of the CS patients, a significant decline in canopy coverage occurred only once bone formation was initiated, but in the remaining third of the CS patients the prevalence of canopies already decreased before bone formation. This canopy loss before initiation of bone formation coincided with significantly less bone-forming surface compared with canopy loss at a later stage. These observations support a model where bone restitution is compromised in the absence of BRC canopies, and apparently does not start when the BRC canopy is lost before initiation of the bone formation step. This model is discussed in the context of possible biological roles of BRC canopies. It suggests that BRC canopies could be privileged targets for treating patients suffering from a negative bone formation-resorption balance. PMID:22162180

Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent; Hauge, Ellen Margrethe; Bollerslev, Jens; Amling, Michael; Barvencik, Florian; Delaissé, Jean-Marie

2012-04-01

45

Early active mobilization following UCL repair With Mitek bone anchor.  

PubMed

Ulnar collateral ligament (UCL) injuries of the thumb are common. Surgical repair is accepted as the treatment of choice for complete rupture of the ligament. Biomechanical studies have suggested that Mitek bone anchor repairs are potentially safe and strong enough to allow early controlled active mobilization. To date, there have been no studies to compare early active mobilization following Mitek bone anchor repair to standard postoperative rehabilitation involving thumb spica immobilization for the first 4 to 6 weeks. We performed a small pilot randomized control trial to assess the outcome of this new rehabilitation technique to that of standard immobilization following UCL repair with Mitek bone anchor. Our results show that on average early active mobilization leads to an earlier return to full hand function (6 vs. 8 wk) and an earlier return to work (7 vs. 11 wk). There is no difference in the final range of motion achieved. We suggest that Mitek bone anchor repairs for UCL ruptures are robust enough to allow early active mobilization and that a larger trial is warranted to assess whether early active mobilization is superior to standard rehabilitation. PMID:23970193

Crowley, Timothy P; Stevenson, Susan; Taghizadeh, Reika; Addison, Patrick; Milner, Richard H

2013-09-01

46

Endochondral bone formation in embryonic mouse pre-metatarsals  

NASA Technical Reports Server (NTRS)

Long term exposure to a reduced gravitational environment has a deleterious effect on bone. The developmental events which occur prior to initial bone deposition will provide insight into the regulation of mature bone physiology. We have characterized a system in which the events preceding bone formation take place in an isolated in vitro organ culture environment. We show that cultured pre-metatarsal tissue parallels development of pre-metatarsal tissue in the embryo. Both undergo mesenchyme differentiation and morphogenesis to form a cartilage rod, which resembles the future bone, followed by terminal chondrocyte differentiation in a definite morphogenetic pattern. These sequential steps occur prior to osteoblast maturation and bone matrix deposition in the developing organism. Alkaline phosphatase (ALP) activity is a distinctive enzymatic marker for mineralizing tissues. We have measured this activity throughout pre-metatarsal development and show (a) where in the tissue it is predominantly found, and (b) that this is indeed the mineralizing isoform of the enzyme.

Klement, B. J.; Spooner, B. S.

1992-01-01

47

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

PubMed Central

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

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

2014-01-01

48

Early excision of heterotopic bone in the forearm  

Microsoft Academic Search

Five patients undergoing early excision of heterotopic bone in the forearm with radiation therapy and indomethacin were reviewed. Inciting causes of heterotopic ossification included distal biceps tendon repairs, ulna fractures, and a fracture of the radius and ulna. Preoperative forearm rotation arc averaged 17°. Excision was performed at an average of 4 months after injury. Patients were administered 500 to

Daphne M. Beingessner; Stuart D. Patterson; Graham J. W. King

2000-01-01

49

The influence of age on adaptive bone formation and bone resorption.  

PubMed

Bone is a tissue with enormous adaptive capacity, balancing resorption and formation processes. It is known that mechanical loading shifts this balance towards an increased formation, leading to enhanced bone mass and mechanical performance. What is not known is how this adaptive response to mechanical loading changes with age. Using dynamic micro-tomography, we show that structural adaptive changes of trabecular bone within the tibia of living mice subjected to two weeks of in vivo cyclic loading are altered by aging. Comparisons of 10, 26 and 78 weeks old animals reveal that the adaptive capacity diminishes. Strikingly, adaptation was asymmetric in that loading increases formation more than it reduces resorption. This asymmetry further shifts the (re)modeling balance towards a net bone loss with age. Loading results in a major increase in the surface area of mineralizing bone. Interestingly, the resorption thickness is independent of loading in trabecular bone in all age groups. This data suggests that during youth, mechanical stimulation induces the recruitment of bone modeling cells whereas in old age, only bone forming cells are affected. These findings provide mechanistic insights into the processes that guide skeletal aging in mice as well as in other mammals. PMID:25128376

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

2014-11-01

50

Expression of bone morphogenic protein in sinonasal inverted papilloma with new bone formation  

PubMed Central

Inverted papilloma (IP) is a common benign tumor in the nose and sinus. Osteogenesis in sinonasal IP is extremely rare; to date, only five cases of IP with new bone formation appear in the literature. In addition, the mechanism of osteogenesis in IP remains unclear. Here, we describe three cases of IP with new bone formation and an investigation into a possible role for bone morphogenic protein (BMP) in osteogenesis. Of three patients with sinonasal IP with new bone formation, two were treated by endoscopic sinus surgery and one was followed up with watchful waiting. Tumor tissues were subjected to immunohistochemistry to detect BMP expression. The patients were successfully treated surgically and showed no evidence of recurrence postoperatively. Follow-up examination is ongoing. Immunohistochemically, the tumors expressed BMP-4 but not BMP-2 or BMP-7. ESS could be successfully used to achieve complete removal of the sinonasal IPs with new bone formation. BMP-4 might be associated with new bone formation in the tumor. PMID:22852110

Okamoto, Tomoyo; Nomi, Nozomi; Umemoto, Shingo; Suzuki, Masashi

2011-01-01

51

Bone formation in rabbit's leg muscle after autologous transplantation of bone marrow-derived mesenchymal stem cells expressing human bone morphogenic protein-2  

PubMed Central

Background: To test whether autologous transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) expressing human bone morphogenic protein-2 (hBMP-2) can produce bone in rabbit leg muscles. Materials and Methods: MSCs were isolated from BM of the iliac crest of rabbits and then infected with lentiviral vectors (LVs) bearing hBMP-2 and green fluorescent protein under the control of the cytomegalovirus (immediate early promoter). Differentiation of transduced MSCs to osteoblasts in vitro was evaluated with an alkaline phosphatase activity assay and immuohistochemistry against osteoblast specific markers. MSCs expressing hBMP-2 were placed in an absorbable gelatin sponge, which was then transplanted into the gastrocnemius of rabbits from which MSCs were isolated. Bone formation was examined by X-ray and histological analysis. Results: LVs efficiently mediated hBMP-2 gene expression in rabbit BM-MSCs. Ectopic expression of hBMP in these MSCs induced osteoblastic differentiation in vitro. Bone was formed after the MSCs expressing hBMP-2 were transplanted into rabbit muscles. Conclusion: Ectopic expression of hBMP-2 in rabbit MSCs induces them to differentiate into osteoblasts in vitro and to form a bone in vivo. PMID:25143636

Wei, Licheng; Lei, Guang-Hua; Yi, Han-Wen; Sheng, Pu-yi

2014-01-01

52

Measurement of spinal or peripheral bone mass to estimate early postmenopausal bone loss  

SciTech Connect

This report presents data from 153 healthy, early postmenopausal women who were randomly allocated to two years of treatment with estrogen or placebo. Bone mineral content in the forearms was measured by single-photon absorptiometry, and bone mineral density of the lumbar spine and total-body bone mineral by dual-photon absorptiometry, before and after one and two years of treatment. At the end of the two years, there were highly significant differences of 6 to 7 percent between the estrogen and the placebo groups at all sites measured. The range of the changes of the spine measurement was twice that of the forearm and total-body measurements. It is concluded that measurement of the forearm by single-photon absorptiometry is superior to measurement of the spine by dual-photon absorptiometry both in clinical studies and in the individual patient for detecting estrogen-dependent bone loss and its treatment by estrogen replacement.

Riis, B.J.; Christiansen, C.

1988-04-01

53

Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers.  

PubMed

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues. PMID:12689681

Saito, N; Okada, T; Horiuchi, H; Ota, H; Takahashi, J; Murakami, N; Nawata, M; Kojima, S; Nozaki, K; Takaoka, K

2003-04-01

54

Recapitulation of signals regulating embryonic bone formation during postnatal growth and in fracture repair  

E-print Network

that regulate embryonic endochondral ossification are also expressed during postnatal bone growth and fracture Ireland Ltd. Keywords: Ihh; Parathyroid hormone-related protein; Fracture repair; Bone; EndochondralRecapitulation of signals regulating embryonic bone formation during postnatal growth

Tabin, Cliff

55

Effects Of Stress On Bone-Formation Markers In Rats  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

56

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

Microsoft Academic Search

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

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

2008-01-01

57

Targeting the Wnt Signaling Pathway to Augment Bone Formation  

PubMed Central

Recent discoveries in humans and mice have revealed that the Wnt (Wingless and Int-1) signaling pathway is responsible for a complex array of functions in maintaining bone homeostasis. The Wnt proteins are key modulators of mesenchymal lineage specification and regulate most aspects of osteoblast physiology and post-natal bone acquisition by controlling the differentiation and activity of osteoblasts and osteoclasts. Initial reports have indicated that activators of Wnt signaling are potent promoters of osteogenesis; however, systemic hyperactivation of the canonical Wnt pathway could potentially accelerate neoplastic transformation and subsequent tumor growth. Alternatively, recent investigations of natural soluble antagonists of Wnt signaling in bone suggest the possibilities of bone-specific therapies targeting the negative regulators of Wnt pathway, especially sclerostin. With this new knowledge, novel pharmacologic interventions that alter Wnt signaling are being evaluated for the management of osteoporosis. In this article, we briefly describe the Wnt signaling elements, their characterized role in bone, and summarize the current knowledge on the potential to enhance bone formation through the manipulation of Wnt signaling antagonists. PMID:19032924

Shahnazari, Mohammad; Yao, Wei; Corr, Maripat; Lane, Nancy E.

2014-01-01

58

Surface microcracks signal osteoblasts to regulate alignment and bone formation.  

PubMed

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 21days 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 microscopy 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

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

2014-11-01

59

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

E-print Network

Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone in disorders of reduced bone mass, we tested whether lithium could improve bone mass in mice. We gavage) and assessed the effect on bone metabolism after 4 weeks of therapy. Lrp5 / mice lack the Wnt coreceptor low

60

Interference with the Microenvironment Support Impairs the De Novo Formation of Bone Metastasis In Vivo  

Microsoft Academic Search

Interference with the microenvironmental growth support is an attractive therapeutic strategy for repressing metastatic tumor growth. Bone is a highly dynamic tissue that is continuously remodeled by bone resorption and subsequent bone formation. Growth factors supporting bone metastatic growth are released especially during bone resorption. Differently from most other tissues, drugs that can limit local turnover, such as bisphosphonates, are

Gabri van der Pluijm; Ivo Que; Bianca Sijmons; Jeroen T Buijs; Antoinette Wetterwald; George N Thalmann; Socrates E Papapoulos; Marco G Cecchini

61

Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation  

Microsoft Academic Search

Osteocytes are the most abundant cells in bone and are ideally located to influence bone turnover through their syncytial relationship with surface bone cells. Osteocyte-derived signals have remained largely enigmatic, but it was recently reported that human osteocytes secrete sclerostin, an inhibitor of bone formation. Absent sclerostin protein results in the high bone mass clinical disorder sclerosteosis. Here we report

Kenneth E. S. Poole; Rutger L. van Bezooijen; Nigel Loveridge; Herman Hamersma; Socrates E. Papapoulos; Clemens W. Löwik; Jonathan Reeve

2005-01-01

62

Protostar formation in the early universe.  

PubMed

The nature of the first generation of stars in the universe remains largely unknown. Observations imply the existence of massive primordial stars early in the history of the universe, and the standard theory for the growth of cosmic structure predicts that structures grow hierarchically through gravitational instability. We have developed an ab initio computer simulation of the formation of primordial stars that follows the relevant atomic and molecular processes in a primordial gas in an expanding universe. The results show that primeval density fluctuations left over from the Big Bang can drive the formation of a tiny protostar with a mass 1% that of the Sun. The protostar is a seed for the subsequent formation of a massive primordial star. PMID:18669856

Yoshida, Naoki; Omukai, Kazuyuki; Hernquist, Lars

2008-08-01

63

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation  

Microsoft Academic Search

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology\\/Principal

Erik Maronde; Arndt F. Schilling; Sebastian Seitz; Thorsten Schinke; Isabelle Schmutz; Horst van der G. T. J; Michael Amling; Urs Albrecht

2010-01-01

64

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

SciTech Connect

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.

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

1986-12-01

65

Craniosynostosis-Associated Fgfr2C342Y Mutant Bone Marrow Stromal Cells Exhibit Cell Autonomous Abnormalities in Osteoblast Differentiation and Bone Formation  

PubMed Central

We recently reported that cranial bones of Fgfr2C342Y/+ craniosynostotic mice are diminished in density when compared to those of wild type mice, and that cranial bone cells isolated from the mutant mice exhibit inhibited late stage osteoblast differentiation. To provide further support for the idea that craniosynostosis-associated Fgfr mutations lead to cell autonomous defects in osteoblast differentiation and mineralized tissue formation, here we tested bone marrow stromal cells isolated from Fgfr2C342Y/+ mice for their ability to differentiate into osteoblasts. Additionally, to determine if the low bone mass phenotype of Crouzon syndrome includes the appendicular skeleton, long bones were assessed by micro CT. Fgfr2C342Y/+ cells showed increased osteoblastic gene expression during early osteoblastic differentiation but decreased expression of alkaline phosphatase mRNA and enzyme activity, and decreased mineralization during later stages of differentiation, when cultured under 2D in vitro conditions. Cells isolated from Fgfr2C342Y/+ mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of Fgfr2C342Y/+ mice. These results demonstrate that marrow stromal cells of Fgfr2C342Y/+ mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the Fgfr2C342Y mutation influences both the axial and appendicular skeletons. PMID:23762837

Liu, J.; Kwon, T.-G.; Nam, H. K.; Hatch, N. E.

2013-01-01

66

Profilin1 regulates sternum development and endochondral bone formation.  

PubMed

Bone development is a dynamic process that requires cell motility and morphological adaptation under the control of actin cytoskeleton. This actin cytoskeleton system is regulated by critical modulators including actin-binding proteins. Among them, profilin1 (Pfn1) is a key player to control actin fiber structure, and it is involved in a number of cellular activities such as migration. During the early phase of body development, skeletal stem cells and osteoblastic progenitor cells migrate to form initial rudiments for future skeletons. During this migration, these cells extend their process based on actin cytoskeletal rearrangement to locate themselves in an appropriate location within microenvironment. However, the role of Pfn1 in regulation of mesenchymal progenitor cells (MPCs) during skeletal development is incompletely understood. Here we examined the role of Pfn1 in skeletal development using a genetic ablation of Pfn1 in MPCs by using Prx1-Cre recombinase. We found that Pfn1 deficiency in MPCs caused complete cleft sternum. Notably, Pfn1-deficient mice exhibited an absence of trabecular bone in the marrow space of appendicular long bone. This phenotype is location-specific, as Pfn1 deficiency did not largely affect osteoblasts in cortical bone. Pfn1 deficiency also suppressed longitudinal growth of long bone. In vitro, Pfn1 deficiency induced retardation of osteoblastic cell migration. These observations revealed that Pfn1 is a critical molecule for the skeletal development, and this could be at least in part associated with the retardation of cell migration. PMID:22773831

Miyajima, Daisuke; Hayata, Tadayoshi; Suzuki, Takafumi; Hemmi, Hiroaki; Nakamoto, Tetsuya; Notomi, Takuya; Amagasa, Teruo; Böttcher, Ralph T; Costell, Mercedes; Fässler, Reinhard; Ezura, Yoichi; Noda, Masaki

2012-09-28

67

Black hole formation in the early Universe  

NASA Astrophysics Data System (ADS)

Supermassive black holes with up to a 109 M? dwell in the centres of present-day galaxies, and their presence has been confirmed at z ? 6. Their formation at such early epochs is still an enigma. Different pathways have been suggested to assemble supermassive black holes in the first billion years after the big bang. Direct collapse has emerged as a highly plausible scenario to form black holes as it provides seed masses of 105-106 M?. Gravitational collapse in atomic cooling haloes with virial temperatures Tvir ? 104 K may lead to the formation of massive seed black holes in the presence of an intense background ultraviolet flux. Turbulence plays a central role in regulating accretion and transporting angular momentum. We present here the highest resolution cosmological large eddy simulations to date which track the evolution of high-density regions on scales of 0.25 au beyond the formation of the first peak, and study the impact of subgrid-scale turbulence. The peak density reached in these simulations is 1.2 × 10-8 g cm-3. Our findings show that while fragmentation occasionally occurs, it does not prevent the growth of a central massive object resulting from turbulent accretion and occasional mergers. The central object reaches ˜1000 M? within four free-fall times, and we expect further growth up to 106 M? through accretion in about 1 Myr. The direct collapse model thus provides a viable pathway of forming high-mass black holes at early cosmic times.

Latif, M. A.; Schleicher, D. R. G.; Schmidt, W.; Niemeyer, J.

2013-08-01

68

Early formation of evolved asteroidal crust.  

PubMed

Mechanisms for the formation of crust on planetary bodies remain poorly understood. It is generally accepted that Earth's andesitic continental crust is the product of plate tectonics, whereas the Moon acquired its feldspar-rich crust by way of plagioclase flotation in a magma ocean. Basaltic meteorites provide evidence that, like the terrestrial planets, some asteroids generated crust and underwent large-scale differentiation processes. Until now, however, no evolved felsic asteroidal crust has been sampled or observed. Here we report age and compositional data for the newly discovered, paired and differentiated meteorites Graves Nunatak (GRA) 06128 and GRA 06129. These meteorites are feldspar-rich, with andesite bulk compositions. Their age of 4.52 +/- 0.06 Gyr demonstrates formation early in Solar System history. The isotopic and elemental compositions, degree of metamorphic re-equilibration and sulphide-rich nature of the meteorites are most consistent with an origin as partial melts from a volatile-rich, oxidized asteroid. GRA 06128 and 06129 are the result of a newly recognized style of evolved crust formation, bearing witness to incomplete differentiation of their parent asteroid and to previously unrecognized diversity of early-formed materials in the Solar System. PMID:19129845

Day, James M D; Ash, Richard D; Liu, Yang; Bellucci, Jeremy J; Rumble, Douglas; McDonough, William F; Walker, Richard J; Taylor, Lawrence A

2009-01-01

69

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

SciTech Connect

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.

Kimura, Hiroaki [Department of Orthopaedics, Kyoto University, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedics, Kyoto University, Kyoto 606-8507 (Japan)]. E-mail: hakiyama@kuhp.kyoto-u.ac.jp; Nakamura, Takashi [Department of Orthopaedics, Kyoto University, Kyoto 606-8507 (Japan); Crombrugghe, Benoit de [Department of Molecular Genetics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030 (United States)

2007-05-18

70

Early planet formation as a trigger for further planet formation  

E-print Network

Recent discoveries of extrasolar planets at small orbital radii, or with significant eccentricities, indicate that interactions between massive planets and the disks of gas and dust from which they formed are vital for determining the final shape of planetary systems. We show that if this interaction occurs at an early epoch, when the protoplanetary disc was still massive, then rapid planet growth through accretion causes an otherwise stable disc to fragment into additional planetary mass bodies when the planetary mass reaches 4-5 Jupiter masses. We suggest that such catastrophic planet formation could account for apparent differences in the mass function of massive planets and brown dwarfs, and the existence of young stars that appear to have dissipated their discs at an early epoch. Subsequent gravitational interactions will lead to planetary systems comprising a small number of massive planets in eccentric orbits.

Philip J. Armitage; Brad M. S. Hansen

1999-12-08

71

Star Formation in Early-type Galaxies  

NASA Astrophysics Data System (ADS)

We use a spectroscopic sample 37,474 early-type galaxies selected by morphology from the second data release of the Sloan Digital Sky Survey to search for actively star-forming early-type galaxies that may be the progenitors of post-star-burst, early-type galaxies referred to as E+A galaxies. Within our sample, we find that about 3% of the galaxies show clear evidence for current star formation. Visual inspection of the most nearby galaxies estimates that about 1/3 of these star forming galaxies are bulge-dominated spiral galaxies; the rest are elliptical or lenticular galaxies. Visual inspection also revealed that a significant fraction of E+A galaxies within the sample are also bulge-dominated spirals. The star forming objects were found on average to be slightly higher surface brightness and to have lower velocity dispersions than the entire sample. The star forming galaxies also have lower velocity dispersions than the E+A galaxies in the sample, but are lower surface brightness. We find that the abundances of E+A and star forming galaxies within our sample both depend on environment in nearly the same way; higher numbers of both types of objects are found in lower density environments. We use population synthesis models to explore the possible distributions for the star formation time scales in these objects. The best fitting scenario requires that the star formation time scale be inversely proportional to the initial SFR and estimates the median time scale to be about 50 Myr with a standard deviation of about 1 dex. The fraction of galaxies with time scales greater than 1 Gyr for this distribution is about 10%. This fraction is significantly lower than what is required to explain the level of alpha-enhancement observed for the entire sample as quantified by the distribution of values for [Mg/Fe] without invoking any change in the initial mass function.

Helmboldt, J. F.; Walterbos, R. A. M.

2004-12-01

72

Core and early crust formation on Mars  

NASA Astrophysics Data System (ADS)

One of the most striking surface features on Mars is the crustal dichotomy. It is the oldest geological feature on Mars and was formed more than 4.1 Ga ago by either exogenic or endogenic processes [1,2]. In order to find an internal origin of the crustal dichotomy, located within a maximum of 400 Ma of planetary differentiation, the thermal state of the planet resulting from core formation needs to be considered. Additionally, it was suggested that a primordial crust with up to 45 km thickness can be formed already during the Martian core formation [3]. We suggest that the sinking of iron diapirs delivered by predifferentiated impactors induced impact- and shear heating-related temperature anomalies in the mantle that fostered the formation of early Martian crust. Thus, the crustal thickness distribution would largely be a result of planetary core formation, late impact history and the onset of mantle convection. To test this hypothesis we use numerical models to simulate the formation of the Martian iron core and the resulting mantle convection pattern, while peridotite melting is enabled to track melting caused by shear and radioactive heating. We perform 2D simulations using the spherical-Cartesian code I2ELVIS for planetary accretion and the spherical code STAGYY for the consequent onset of mantle convection. We apply a temperature-, stress- and melt-fraction dependent viscoplastic rheology. Radioactive and shear heating as well as consumption of latent heat by silicate melting are taken into account. The depth of neutral buoyancy of silicate melt with respect to solid silicates is determined by the difference in compressibility of the liquid and solid phase. To self-consistently simulate the silicate phase changes expected inside a Mars-sized body, we use the thermodynamical database Perple_X. As initial condition for core formation, we apply randomly distributed iron diapirs with 75 km radius inside the planet, representing the cores of stochastically distributed impactors. Additionally, we explore the effect of one giant impactor core on the planetary evolution. Results indicate that the presence of a large impactor core induces hemispherically asymmetrical core formation. The amplitude of shear heating anomalies often exceeds the solidus of primitive mantle material and thus, the formation of a considerable amount of silicate melt is observed. The resulting temperature field after core formation is then read into the mantle convection code STAYY. The hemispherical magma ocean induced by one late giant impactor favours a dichotomous crust formation during and shortly after core formation. Afterwards, the extraction of excess heat produced by the sinking of the giant impactor through the mantle leads to a localized region of massive magmatism, comparable to Tharsis, which is sustained during later evolution by a single plume forming beneath the province. The rest of the mantle is dominated by a sluggish convection pattern with limited crust formation that preserves the early formed dichotomous crustal structure until recent time. References [1] Nimmo, F. et al., Nature, 453, 1220-1223, 2008. [2] Keller, T. & Tackley, P.J., Icarus, 202, 429-443, 2009. [3] Norman, M.D., Meteorit. Planet. Sci., 34, 439-449, 1999.

Golabek, G. J.; Keller, T.; Gerya, T.; Tackley, P. J.; Connolly, J.; Zhu, G.

2010-12-01

73

Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair  

PubMed Central

Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1?/? mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1?/? mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1?/? callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

2011-01-01

74

Computational simulation of the early stage of bone healing under different configurations of locking compression plates.  

PubMed

Flexible fixation or the so-called 'biological fixation' has been shown to encourage the formation of fracture callus, leading to better healing outcomes. However, the nature of the relationship between the degree of mechanical stability provided by a flexible fixation and the optimal healing outcomes has not been fully understood. In this study, we have developed a validated quantitative model to predict how cells in fracture callus might respond to change in their mechanical microenvironment due to different configurations of locking compression plate (LCP) in clinical practice, particularly in the early stage of healing. The model predicts that increasing flexibility of the LCP by changing the bone-plate distance (BPD) or the plate working length (WL) could enhance interfragmentary strain in the presence of a relatively large gap size (>3 mm). Furthermore, conventional LCP normally results in asymmetric tissue development during early stage of callus formation, and the increase of BPD or WL is insufficient to alleviate this problem. PMID:24261957

Miramini, Saeed; Zhang, Lihai; Richardson, Martin; Pirpiris, Marinis; Mendis, Priyan; Oloyede, Kunle; Edwards, Glenn

2015-06-01

75

MicroRNA control of bone formation and homeostasis  

Microsoft Academic Search

MicroRNAs (miRNAs) repress cellular protein levels to provide a sophisticated parameter of gene regulation that coordinates a broad spectrum of biological processes. Bone organogenesis is a complex process involving the differentiation and crosstalk of multiple cell types for formation and remodeling of the skeleton. Inhibition of mRNA translation by miRNAs has emerged as an important regulator of developmental osteogenic signaling

Gary S. Stein; Andre J. van Wijnen; Janet L. Stein; Mohammad Q. Hassan; Tripti Gaur; Ying Zhang; Jane B. Lian

2012-01-01

76

The role of middle ear effusions and epidermal growth factor in cholesteatoma formation in the gerbilline temporal bone  

Microsoft Academic Search

To study the process of aural cholesteatoma formation, we used gerbilline temporal bones to examine histologically the early stages of spontaneous cholesteatomas associated with experimentally induced otitis media with effusion (OME) following electric cauterizations of the eustachian tube. Epidermal growth factor (EGF) was then localized immunohistochemically in the pars flaccida of normal ears and the forming spontaneous cholesteatomas. Findings in

F. Omura; K. Makino; M. Amatsu; H. Itoh

1995-01-01

77

Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II  

PubMed Central

Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency of numerous acid hydrolases results in accumulation of storage material in chondrocytes and osteoblasts, and impaired bone formation. In osteoclasts, no morphological or functional abnormalities are detected whereas osteoclastogenesis is dramatically increased in MLII mice. The high number of osteoclasts in MLII is associated with enhanced osteoblastic expression of the pro-osteoclastogenic cytokine interleukin-6, and pharmacological inhibition of bone resorption prevented the osteoporotic phenotype of MLII mice. Our findings show that progressive bone loss in MLII is due to the presence of dysfunctional osteoblasts combined with excessive osteoclastogenesis. They further underscore the importance of a deep skeletal phenotyping approach for other lysosomal diseases in which bone loss is a prominent feature. PMID:24127423

Kollmann, Katrin; Pestka, Jan Malte; Kuhn, Sonja Christin; Schone, Elisabeth; Schweizer, Michaela; Karkmann, Kathrin; Otomo, Takanobu; Catala-Lehnen, Philip; Failla, Antonio Virgilio; Marshall, Robert Percy; Krause, Matthias; Santer, Rene; Amling, Michael; Braulke, Thomas; Schinke, Thorsten

2013-01-01

78

Targeted deletion of Sost distal enhancer increases bone formation and bone mass  

PubMed Central

The Wnt antagonist Sost has emerged as a key regulator of bone homeostasis through the modulation of Lrp4/5/6 Wnt coreceptors. In humans, lack of Sclerostin causes sclerosteosis and van Buchem (VB) disease, two generalized skeletal hyperostosis disorders that result from hyperactive Wnt signaling. Unlike sclerosteosis, VB patients lack SOST coding mutations but carry a homozygous 52 kb noncoding deletion that is essential for the transcriptional activation of SOST in bone. We recently identified a putative bone enhancer, ECR5, in the VB deletion region, and showed that the transcriptional activity of ECR5 is controlled by Mef2C transcription factor in vitro. Here we report that mice lacking ECR5 or Mef2C through Col1-Cre osteoblast/osteocyte-specific ablation result in high bone mass (HBM) due to elevated bone formation rates. We conclude that the absence of the Sost-specific long-range regulatory element ECR5 causes VB disease in rodents, and that Mef2C is the main transcription factor responsible for ECR5-dependent Sost transcriptional activation in the adult skeleton. PMID:22886088

Collette, Nicole M.; Genetos, Damian C.; Economides, Aris N.; Xie, LiQin; Shahnazari, Mohammad; Yao, Wei; Lane, Nancy E.; Harland, Richard M.; Loots, Gabriela G.

2012-01-01

79

Abdominal Fat Is Associated With Lower Bone Formation and Inferior Bone Quality in Healthy Premenopausal Women: A Transiliac Bone Biopsy Study  

PubMed Central

Context: The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation. Objective: The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights. Design: We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies. Results: Body mass index (BMI) ranged from 20.1 to 39.2 kg/m2. Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm2/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = ?0.50; P < .01) and bone formation rate (r = ?0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI. Conclusions: At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation. PMID:23515452

Dempster, David W.; Recker, Robert R.; Lappe, Joan M.; Zhou, Hua; Zwahlen, Alexander; Muller, Ralph; Zhao, Binsheng; Guo, Xiaotao; Lang, Thomas; Saeed, Isra; Liu, X. Sherry; Guo, X. Edward; Cremers, Serge; Rosen, Clifford J.; Stein, Emily M.; Nickolas, Thomas L.; McMahon, Donald J.; Young, Polly; Shane, Elizabeth

2013-01-01

80

Recent Advances in the Use of Serological Bone Formation Markers to Monitor Callus Development and Fracture Healing  

PubMed Central

The failure of an osseous fracture to heal, or the development of a nonunion, is common; however, current diagnostic measures lack the capability of early and reliable detection of such events. Analyses of radiographic imaging and clinical examination, in combination, remain the gold standard for diagnosis; however, these methods are not reliable for early detection. Delayed diagnosis of a nonunion is costly from both the patient and treatment standpoints. In response, repeated efforts have been made to identify bone metabolic markers as diagnostic or prognostic tools for monitoring bone healing. Thus far, the evidence regarding a correlation between the kinetics of most bone metabolic markers and nonunion is very limited. With the aim of classifying the role of biological pathways of bone metabolism and of understanding bone conditions in the development of osteoporosis, advances have been made in our knowledge of the molecular basis of bone remodeling, fracture healing, and its failure. Procollagen type I amino-terminal propeptide has been shown to be a reliable bone formation marker in osteoporosis therapy and its kinetics during fracture healing has been recently described. In this article, we suggest that procollagen type I amino-terminal propeptide presents a good opportunity for early detection of nonunion. We also review the role and potential of serum PINP, as well as other markers, as indications of fracture healing. PMID:21133841

Coulibaly, Marlon O.; Sietsema, Debra L.; Burgers, Travis A.; Mason, Jim; Williams, Bart O.; Jones, Clifford B.

2011-01-01

81

Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis  

Microsoft Academic Search

Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured

Seth W. Donahue; Sarah A. Galley; Michael R. Vaughan; Patricia Patterson-Buckendahl; Laurence M. Demers; Josef L. Vance; Meghan E. McGee

2006-01-01

82

SOST\\/sclerostin, an osteocyte-derived negative regulator of bone formation  

Microsoft Academic Search

Sclerosteosis and Van Buchem disease are two closely related bone disorders characterized by progressive bone thickening due to increased bone formation. Sclerosteosis is associated with mutations in the SOST gene and Van Buchem disease with a 52kb deletion downstream of the SOST gene that probably affects transcription of the gene. Expression of the gene product sclerostin in bone is restricted

Rutger L. van Bezooijen; Peter ten Dijke; Socrates E. Papapoulos; Clemens W. G. M. Löwik

2005-01-01

83

Cinacalcet Decreases Bone Formation Rate in Hypercalcemic Hyperparathyroidism after Kidney Transplantation  

Microsoft Academic Search

Background\\/Aims: Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. Its effect on bone, however, has not been investigated in this population. Methods: We prospectively examined bone turnover, histomorphometry and density as well as serum bone biomarkers in 10 transplant recipients before and after treatment with cinacalcet. Results: After 18–24 months of treatment with cinacalcet, bone formation decreased

Kyra A. Borchhardt; Danielle Diarra; Irene Sulzbacher; Thomas Benesch; Martin Haas; Gere Sunder-Plassmann

2010-01-01

84

Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats  

PubMed Central

Background Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. Methods Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml) for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 ?L of zoledronic acid solution (0.5 mg/ml) was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg) systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV) of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. Results In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007). In all groups receiving zoledronic acid, the BV/TV was higher compared to control. Conclusions This study found a strong inhibitory effect on bone resorption by bisphosphonates but also a limited inhibition of the ingrowth of new bone. Local treatment at surgery resulted in stronger inhibition of both resorption and bone formation compared to systemic treatment. PMID:23217097

2012-01-01

85

Does locally delivered Zoledronate influence peri-implant bone formation? - Spatio-temporal monitoring of bone remodeling in vivo.  

PubMed

Bisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on peri-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronate-loaded hydrogel for enhancement of peri-implant bone volume which is directly linked to improved implant fixation. PMID:25241159

Kettenberger, Ulrike; Ston, Julien; Thein, Eric; Procter, Philip; Pioletti, Dominique P

2014-12-01

86

Biglycan modulates angiogenesis and bone formation during fracture healing.  

PubMed

Matrix proteoglycans such as biglycan (Bgn) dominate skeletal tissue and yet its exact role in regulating bone function is still unclear. In this paper we describe the potential role of (Bgn) in the fracture healing process. We hypothesized that Bgn could regulate fracture healing because of previous work showing that it can affect normal bone formation. To test this hypothesis, we created fractures in femurs of 6-week-old male wild type (WT or Bgn+/0) and Bgn-deficient (Bgn-KO or Bgn-/0) mice using a custom-made standardized fracture device, and analyzed the process of healing over time. The formation of a callus around the fracture site was observed at both 7 and 14 days post-fracture in WT and Bgn-deficient mice and immunohistochemistry revealed that Bgn was highly expressed in the fracture callus of WT mice, localizing within woven bone and cartilage. Micro-computed tomography (?CT) analysis of the region surrounding the fracture line showed that the Bgn-deficient mice had a smaller callus than WT mice. Histology of the same region also showed the presence of less cartilage and woven bone in the Bgn-deficient mice compared to WT mice. Picrosirius red staining of the callus visualized under polarized light showed that there was less fibrillar collagen in the Bgn-deficient mice, a finding confirmed by immunohistochemistry using antibodies to type I collagen. Interestingly, real time RT-PCR of the callus at 7 days post-fracture showed a significant decrease in relative vascular endothelial growth factor A (VEGF) gene expression by Bgn-deficient mice as compared to WT. Moreover, VEGF was shown to bind directly to Bgn through a solid-phase binding assay. The inability of Bgn to directly enhance VEGF-induced signaling suggests that Bgn has a unique role in regulating vessel formation, potentially related to VEGF storage or stabilization in the matrix. Taken together, these results suggest that Bgn has a regulatory role in the process of bone formation during fracture healing, and further, that reduced angiogenesis could be the molecular basis. PMID:24373744

Berendsen, Agnes D; Pinnow, Emily L; Maeda, Azusa; Brown, Aaron C; McCartney-Francis, Nancy; Kram, Vardit; Owens, Rick T; Robey, Pamela G; Holmbeck, Kenn; de Castro, Luis F; Kilts, Tina M; Young, Marian F

2014-04-01

87

Dissociation of Bone Resorption and Bone Formation in Adult Mice with a Non-Functional V-ATPase in Osteoclasts Leads to Increased Bone Strength  

PubMed Central

Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption. To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks. Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for µCT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. µCT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone. In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength. PMID:22087326

Henriksen, Kim; Flores, Carmen; Thomsen, Jesper S.; Bruel, Anne-Marie; Thudium, Christian S.; Neutzsky-Wulff, Anita V.; Langenbach, Geerling E. J.; Sims, Natalie; Askmyr, Maria; Martin, Thomas J.; Everts, Vincent; Karsdal, Morten A.; Richter, Johan

2011-01-01

88

Ectopic bone formation associated with mesenchymal stem cells in a resorbable calcium deficient hydroxyapatite carrier  

Microsoft Academic Search

Bone substitute materials can induce bone formation in combination with mesenchymal stem cells (MSC). The aim of the current study was to examine ectopic in vivo bone formation with and without MSC on a new resorbable ceramic, called calcium deficient hydroxyapatite (CDHA). Ceramic blocks characterized by a large surface (48m2\\/g) were compared with ?-tricalcium phosphate (?-TCP), hydroxyapatite (HA) ceramics (both

Philip Kasten; Julia Vogel; Reto Luginbühl; Philip Niemeyer; Marcus Tonak; Helga Lorenz; Lars Helbig; Stefan Weiss; Jörg Fellenberg; Albrecht Leo; Hans-Georg Simank; Wiltrud Richter

2005-01-01

89

Histomorphometric evaluation of new bone formation in diabetic rats submitted to insertion of temporary implants  

Microsoft Academic Search

This study aimed to quantify new bone formation in the femurs of diabetic Wistar rats. Over an eight-week period, MTI-MP® implants were evaluated in control rats and in diabetic rats. At several points during this period, various markers for bone deposit were introduced. The material was observed under fluorescent light microscopy. New bone formation in periosteal and cortical regions linked

Cyro Eduardo de Carvalho; Renato Paulo Chopard

2004-01-01

90

Essential physics of early galaxy formation  

NASA Astrophysics Data System (ADS)

We present a theoretical model embedding the essential physics of early galaxy formation (z ? 5-12) based on the single premise that any galaxy can form stars with a maximal limiting efficiency that provides enough energy to expel all the remaining gas, quenching further star formation. This simple idea is implemented into a merger-tree-based semi-analytical model that utilizes two mass and redshift-independent parameters to capture the key physics of supernova feedback in ejecting gas from low-mass haloes, and tracks the resulting impact on the subsequent growth of more massive systems via halo mergers and gas accretion. Our model shows that: (i) the smallest haloes (halo mass Mh ? 1010 M?) build up their gas mass by accretion from the intergalactic medium; (ii) the bulk of the gas powering star formation in larger haloes (Mh ? 1011.5 M?) is brought in by merging progenitors; (iii) the faint-end UV luminosity function slope evolves according to ? = -1.75 log z - 0.52. In addition, (iv) the stellar mass-to-light ratio is well fitted by the functional form log M* = -0.38MUV - 0.13 z + 2.4, which we use to build the evolving stellar mass function to compare to observations. We end with a census of the cosmic stellar mass density (SMD) across galaxies with UV magnitudes over the range -23 ? MUV ? -11 spanning redshifts 5 < z < 12; (v) while currently detected LBGs contain ?50 per cent (10 per cent) of the total SMD at z = 5 (8), the James Webb Space Telescope will detect up to 25 per cent of the SMD at z ? 9.5.

Dayal, Pratika; Ferrara, Andrea; Dunlop, James S.; Pacucci, Fabio

2014-12-01

91

Developing bones are differentially affected by compromised skeletal muscle formation  

PubMed Central

Mechanical forces are essential for normal adult bone function and repair, but the impact of prenatal muscle contractions on bone development remains to be explored in depth in mammalian model systems. In this study, we analyze skeletogenesis in two ‘muscleless’ mouse mutant models in which the formation of skeletal muscle development is disrupted; Myf5nlacZ/nlacZ:MyoD?/? and Pax3Sp/Sp (Splotch). Ossification centers were found to be differentially affected in the muscleless limbs, with significant decreases in bone formation in the scapula, humerus, ulna and femur, but not in the tibia. In the scapula and humerus, the morphologies of ossification centers were abnormal in muscleless limbs. Histology of the humerus revealed a decreased extent of the hypertrophic zone in mutant limbs but no change in the shape of this region. The elbow joint was also found to be clearly affected with a dramatic reduction in the joint line, while no abnormalities were evident in the knee. The humeral deltoid tuberosity was significantly reduced in size in the Myf5nlacZ/nlacZ:MyoD?/? mutants while a change in shape but not in size was found in the humeral tuberosities of the Pax3Sp/Sp mutants. We also examined skeletal development in a ‘reduced muscle’ model, the Myf5nlacZ/+:MyoD?/? mutant, in which skeletal muscle forms but with reduced muscle mass. The reduced muscle phenotype appeared to have an intermediate effect on skeletal development, with reduced bone formation in the scapula and humerus compared to controls, but not in other rudiments. In summary, we have demonstrated that skeletal development is differentially affected by the lack of skeletal muscle, with certain rudiments and joints being more severely affected than others. These findings indicate that the response of skeletal progenitor cells to biophysical stimuli may depend upon their location in the embryonic limb, implying a complex interaction between mechanical forces and location-specific regulatory factors affecting bone and joint development. PMID:19948261

Nowlan, Niamh C.; Bourdon, Celine; Dumas, Gerard; Tajbakhsh, Shahragim; Prendergast, Patrick J.; Murphy, Paula

2010-01-01

92

MgCHA particles dispersion in porous PCL scaffolds: in vitro mineralization and in vivo bone formation.  

PubMed

In this work, we focus on the in vitro and in vivo response of composite scaffolds obtained by incorporating Mg,CO3 -doped hydroxyapatite (HA) particles in poly(?-caprolactone) (PCL) porous matrices. After a complete analysis of chemical and physical properties of synthesized particles (i.e. SEM/EDS, DSC, XRD and FTIR), we demonstrate that the Mg,CO3 doping influences the surface wettability with implications upon cell-material interaction and new bone formation mechanisms. In particular, ion substitution in apatite crystals positively influences the early in vitro cellular response of human mesenchymal stem cells (hMSCs), i.e. adhesion and proliferation, and promotes an extensive mineralization of the scaffold in osteogenic medium, thus conforming to a more faithful reproduction of the native bone environment than undoped HA particles, used as control in PCL matrices. Furthermore, we demonstrate that Mg,CO3 -doped HA in PCL scaffolds support the in vivo cellular response by inducing neo-bone formation as early as 2?months post-implantation, and abundant mature bone tissue at the sixth month, with a lamellar structure and completely formed bone marrow. Together, these results indicate that Mg(2+) and CO3 (2-) ion substitution in HA particles enhances the scaffold properties, providing the right chemical signals to combine with morphological requirements (i.e. pore size, shape and interconnectivity) to drive osteogenic response in scaffold-aided bone regeneration. PMID:22730225

Guarino, Vincenzo; Scaglione, Silvia; Sandri, Monica; Alvarez-Perez, Marco A; Tampieri, Anna; Quarto, Rodolfo; Ambrosio, Luigi

2014-04-01

93

Bone Resorption Increases as Early as the Second Day in Head- Down Bed Rest  

NASA Astrophysics Data System (ADS)

Long-term bed rest and space mission studies have shown that immobilization as well as microgravity induce increased bone resorption while bone formation tends to decrease. In order to analyze the kinetics of short-term changes in bone turnover we studied in a randomized, strictly controlled crossover design the effects of 6 days 6° head-down tilt bed rest (HDT) in 8 male healthy subjects (mean body weight (BW): 70.1 +/- 1.88 kg; mean age: 25.5 +/- 1.04 years) in our metabolic ward. Two days before arriving in the metabolic ward the subjects started with a diet consisting of an energy content of 10 MJ/d, 2000 mg Calcium/d, 400 i.U. Vitamin D, 200 mEq Na+ and 50 ml water/kg BW/d. The diet was continued in the metabolic ward. The metabolic ward period (11days) was divided into 3 parts: 4 ambulatory days, 6 days either HDT or control and 1 recovery day. Continuous urine collection started on the first day in the metabolic ward to analyze calcium excretion and bone resorption markers, namely C-telopeptide (CTX) and N-telopeptide (NTX). On the 2nd ambulatory day in the metabolic ward and on the 5th day in HDT or control blood was drawn to analyze serum calcium, parathyroid hormone, and bone formation markers (bone Alkaline Phosphatase (bAP), Procollagen-I-Propeptide (P-I-CP). Both study phases were identical with respect to environmental conditions, study protocol and diet. Urinary calcium excretion was as early as the first day in immobilization increased (p<0.01). CTX- and NTX-excretion stayed unchanged the first 24 hours in HDT compared to the control. But, already on the 2nd day of immobilization both bone resorption markers significantly increased. NTX-excretion was increased by 28.7 +/- 14.0% (p<0.05), while CTX-excretion rose by 17.8 +/- 8.3% (p<0.01). Both, the CTX- excretion as well as the calcium excretion keep the significantly higher level during the HDT period, and even continued through the first day of recovery. However, NTX excretion, descended from day three until the end of HDT. But, the level of NTX excretion during HDT was always higher than during control. In contrast to the bone resorption markers, the formation marker P-I-CP tended to decrease as early as the fifth day of immobilization (p<0.10). Serum calcium-, parathyroid hormone-, as well as bAP concentrations were unchanged. We conclude from these results of a pronounced rise of bone resorption markers that already 24 hours of immobilization induce a significant rise in osteoclast activity in healthy subjects. Thus, it appears possible to use short-term bed rest studies for the development of countermeasures to immobilization osteoporosis and to avoid long-term studies, which presently impose major detectable changes on the health status of healthy human subjects. Further studies are mandatory to investigate the underlying mechanisms and respective countermeasures.

Heer, M.; Kamps, N.; Mika, C.; Boese, A.; Gerzer, R.

94

The Clock Genes Period 2 and Cryptochrome 2 Differentially Balance Bone Formation  

Microsoft Academic Search

BackgroundClock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype.Methodology\\/Principal FindingsWe found

Erik Maronde; Arndt F. Schilling; Sebastian Seitz; Thorsten Schinke; Isabelle Schmutz; Gijsbertus van der Horst; Michael Amling; Urs Albrecht; Dong-Yan Jin

2010-01-01

95

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

PubMed Central

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

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

2013-01-01

96

Constitutively Active PTH/PTHrP Receptor Specifically Expressed in Osteoblasts Enhances Bone Formation Induced by Bone Marrow Ablation  

PubMed Central

Bone is maintained by continuous bone formation by osteoblasts provided by proliferation and differentiation of osteoprogenitors. Parathyroid hormone (PTH) activates bone formation, but because of the complexity of cells in the osteoblast lineage, how these osteoprogenitors are regulated by PTH in vivo is incompletely understood. To elucidate how signals by PTH in differentiated osteoblasts regulate osteoprogenitors in vivo, we conducted bone marrow ablation using Col1a1-constitutively active PTH/PTHrP receptor (caPPR) transgenic mice. These mice express caPPR specifically in osteoblasts by using 2.3 kb Col1a1 promoter and showed higher trabecular bone volume under steady-state conditions. In contrast, after bone marrow ablation, stromal cells recruited from bone surface extensively proliferated in the marrow cavity in transgenic mice, compared to limited proliferation in wild-type mice. Whereas de novo bone formation was restricted to the ablated area in wild-type mice, the entire marrow cavity, including not only ablated area but also outside the ablated area, was filled with newly formed bone in transgenic mice. Bone mineral density was significantly increased after ablation in transgenic mice. Bone marrow cell culture in osteogenic medium revealed that alkaline phosphatase-positive area was markedly increased in the cells obtained from transgenic mice. Furthermore, mRNA expression of Wnt-signaling molecules such as LRP5, Wnt7b, and Wnt10b were upregulated after marrow ablation in bone marrow cells of transgenic mice. These results indicate that constitutive activation of PTH/PTHrP receptor in differentiated osteoblasts enhances bone marrow ablation-induced recruitment, proliferation, and differentiation of osteoprogenitors. PMID:21866553

ONO, NORIAKI; NAKASHIMA, KAZUHISA; SCHIPANI, ERNESTINA; HAYATA, TADAYOSHI; EZURA, YOICHI; SOMA, KUNIMICHI; KRONENBERG, HENRY M.; NODA, MASAKI

2013-01-01

97

Enhancement of bone morphogenetic protein-2 expression and bone formation by coumarin derivatives via p38 and ERK-dependent pathway in osteoblasts  

Microsoft Academic Search

Osteoporosis is a reduction in skeletal mass due to an imbalance between bone resorption and bone formation. Bone morphogenetic protein (BMP) plays important roles in osteoblastic differentiation and bone formation. Therefore, components involved in BMP activation are good targets for the development of anti-osteoporosis drugs. In this study, imperatorin and bergapten, two coumarin derivatives, were shown to enhance alkaline phosphatase

Chih-Hsin Tang; Rong-Sen Yang; Mei-Yin Chien; Chien-Chich Chen; Wen-Mei Fu

2008-01-01

98

Analysis of the dynamics of bone formation, effect of cell seeding density, and potential of allogeneic cells in cell-based bone tissue engineering in goats.  

PubMed

After decades of research, relatively little is known about the role of bone marrow stromal cells (BMSCs) for bone tissue engineering. Although homogeneous cell seeding is regarded optimal, cell survival in large constructs is unlikely, except for the very periphery. Also no minimal and optimal BMSC densities have been identified. An interesting development is the use of allogeneic BMSCs. These have not yet been compared directly to autologous BMSCs. Culture-expanded BMSCs of 10 Dutch milk goats were cryopreserved and peroperatively seeded on 7 mm cubic scaffolds of 65% porous biphasic calcium phosphate (BCP). A range of BMSC densities (per cm3 scaffold) were prepared of 8E2 (= 8 x 10(2)), 8E3, 8E4, 8E5, 8E6 (considered the standard), and 1.6E7. Each goat received a control without cells, the six densities, and an 8E6 allogeneic BMSCs construct intramuscularly. After 3, 5, and 7 weeks, fluorochrome markers were administrated. At 9 weeks, implants were retrieved. The BCP scaffolds appeared to be autoinductive as the controls (without BMSCs) showed some bone. Early bone formation (before 3 weeks) appeared only at the peripheral 2mm of the BMSC-seeded constructs; the later 5- and 9-week labels were found more centrally, suggesting bone migration to the center. There was a minimum of 8E4 and optimum of 8E6 BMSCs/cm3. Allogeneic cells yielded comparable new bone. PMID:18558815

Kruyt, Moyo; De Bruijn, Joost; Rouwkema, Jeroen; Van Bliterswijk, Clemens; Oner, Cumhur; Verbout, Ab; Dhert, Wouter

2008-06-01

99

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

NASA Astrophysics Data System (ADS)

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.

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

2013-11-01

100

BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing  

E-print Network

BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time. In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked. Although other

Tabin, Cliff

101

Connexin 43 Deficiency Attenuates Loss of Trabecular Bone and Prevents Suppression of Cortical Bone Formation During Unloading  

PubMed Central

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and has been demonstrated as an integral component of skeletal homeostasis. In the present study, we sought to further refine the role of Cx43 in the response to mechanical unloading by subjecting skeletally mature mice with a bone-specific deletion of Cx43 (cKO) to three weeks of mechanical unloading via hindlimb suspension (HLS). The HLS model was selected to recapitulate the effects of skeletal unloading due to prolonged bed rest, reduced activity associated with aging, and spaceflight microgravity. At baseline, the cortical bone of cKO mice displayed an osteopenic phenotype, with expanded cortices, decreased cortical thickness, decreased bone mineral density, and increased porosity. There was no baseline trabecular phenotype. Following three weeks of HLS, wild-type (WT) mice experienced substantial declines in trabecular bone volume fraction, connectivity density, trabecular thickness, and trabecular tissue mineral density. These deleterious effects were attenuated in cKO mice. Conversely, there was a similar and significant amount of cortical bone loss in both WT and cKO. Interestingly, mechanical testing revealed a greater loss of strength and rigidity for cKO during HLS. Analysis of double-label quantitative histomorphometry data demonstrated a substantial decrease in bone formation rate, mineralizing surface, and mineral apposition rate at both the periosteal and endocortical surfaces of the femur following unloading of WT mice. This suppression of bone formation was not observed in cKO mice, where parameters were maintained at baseline levels. Taken together, the results of the present study indicate that Cx43 deficiency desensitizes bone to the effects of mechanical unloading, and that this may be due to an inability of mechanosensing osteocytes to effectively communicate the unloading state to osteoblasts to suppress bone formation. Cx43 may represent a novel therapeutic target for investigation as a countermeasure for age-related and unloading-induced bone loss. PMID:22714552

Lloyd, Shane A.; Lewis, Gregory S.; Zhang, Yue; Paul, Emmanuel M.; Donahue, Henry J.

2013-01-01

102

Star Formation in Early-type Galaxies  

Microsoft Academic Search

We use a spectroscopic sample 37,474 early-type galaxies selected by morphology from the second data release of the Sloan Digital Sky Survey to search for actively star-forming early-type galaxies that may be the progenitors of post-star-burst, early-type galaxies referred to as E+A galaxies. Within our sample, we find that about 3% of the galaxies show clear evidence for current star

J. F. Helmboldt; R. A. M. Walterbos

2004-01-01

103

Racial differences in cortical bone and their relationship to biochemical variables in black and white children in the early stages of puberty  

PubMed Central

Introduction Racial differences in bone structure likely have roots in childhood as bone size develops predominantly during growth. This study aimed to compare cortical bone health within the tibial diaphysis of black and white children in the early stages of puberty, and explore the contributions of biochemical variables in explaining racial variation in cortical bone properties. Methods A cross-sectional study was performed comparing peripheral quantitative computed tomography-derived cortical bone measures of the tibial diaphysis and biochemical variables in 314 participants (n=155 males; n=164 blacks) in the early stages of puberty. Results Blacks had greater cortical volumetric bone mineral density, mass and size compared to whites (all p<0.01), contributing to blacks having 17.0% greater tibial strength (polar strength-strain index [SSIP]) (p<0.001). Turnover markers indicated blacks had higher bone formation (osteocalcin [OC] and bone specific alkaline phosphatase) and lower bone resorption (N-terminal telopeptide) than whites (all p<0.01). Blacks also had lower 25-hydroxyvitamin D [25(OH)D], and higher 1,25-dihydroxyvitamin D [1,25(OH)2D] and parathyroid hormone (PTH) (all p<0.05). There were no correlations between tibial bone properties, and 25(OH)D and PTH in whites (all p?0.10); however, SSIP was negatively and positively correlated with 25(OH)D and PTH in blacks, respectively (all p?0.02). Variation in bone cross-sectional area and SSIP attributable to race was partially explained by tibial length, 25(OH)D/PTH and OC. Conclusions Divergence in tibial cortical bone properties between blacks and whites is established by the early stages of puberty with the enhanced cortical bone properties in black children possibly being explained by higher PTH and OC. PMID:23093348

Warden, Stuart J.; Hill, Kathleen M.; Ferira, Ashley J.; Laing, Emma M.; Martin, Berdine R.; Hausman, Dorothy B.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.

2014-01-01

104

Type XII collagen regulates osteoblast polarity and communication during bone formation  

PubMed Central

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

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

2011-01-01

105

Rat adipose-derived stromal cells expressing BMP4 induce ectopic bone formation in vitro and in vivo  

Microsoft Academic Search

Aim:Bone morphogenetic protein 4 (BMP4) is one of the main local contributing factors in callus formation in the early phase of fracture healing. Adipose-derived stromal cells (ADSC) are multipotent cells. The present study was conducted to investigate the osteogenic potential of ADSC when exposed to adenovirus containing BMP4 cDNA (Ad-BMP4).Methods:ADSC were harvested from Sprague-Dawley rats. After exposure to Ad-BMP4, ADSC

Lin Lin; Xin Fu; Xin Zhang; Lian-xu Chen; Ji-ying Zhang; Chang-long Yu; Kang-tao Ma; Chun-yan Zhou

2006-01-01

106

Estrogen receptor-? in osteocytes is important for trabecular bone formation in male mice  

PubMed Central

The bone-sparing effect of estrogen in both males and females is primarily mediated via estrogen receptor-? (ER?), encoded by the Esr1 gene. ER? in osteoclasts is crucial for the trabecular bone-sparing effect of estrogen in females, but it is dispensable for trabecular bone in male mice and for cortical bone in both genders. We hypothesized that ER? in osteocytes is important for trabecular bone in male mice and for cortical bone in both males and females. Dmp1-Cre mice were crossed with ER?flox/flox mice to generate mice lacking ER? protein expression specifically in osteocytes (Dmp1-ER??/?). Male Dmp1-ER??/? mice displayed a substantial reduction in trabecular bone volume (?20%, P < 0.01) compared with controls. Dynamic histomorphometry revealed reduced bone formation rate (?45%, P < 0.01) but the number of osteoclasts per bone surface was unaffected in the male Dmp1-ER??/? mice. The male Dmp1-ER??/? mice had reduced expression of several osteoblast/osteocyte markers in bone, including Runx2, Sp7, and Dmp1 (P < 0.05). Gonadal intact Dmp1-ER??/? female mice had no significant reduction in trabecular bone volume but ovariectomized Dmp1-ER??/? female mice displayed an attenuated trabecular bone response to supraphysiological E2 treatment. Dmp1-ER??/? mice of both genders had unaffected cortical bone. In conclusion, ER? in osteocytes regulates trabecular bone formation and thereby trabecular bone volume in male mice but it is dispensable for the trabecular bone in female mice and the cortical bone in both genders. We propose that the physiological trabecular bone-sparing effect of estrogen is mediated via ER? in osteocytes in males, but via ER? in osteoclasts in females. PMID:23345419

Windahl, Sara H.; Borjesson, Anna E.; Farman, Helen H.; Engdahl, Cecilia; Moverare-Skrtic, Sofia; Sjogren, Klara; Lagerquist, Marie K.; Kindblom, Jenny M.; Koskela, Antti; Tuukkanen, Juha; Divieti Pajevic, Paola; Feng, Jian Q.; Dahlman-Wright, Karin; Antonson, Per; Gustafsson, Jan-Ake; Ohlsson, Claes

2013-01-01

107

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

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.

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

2014-01-01

108

Beta-catenin signaling pathway is crucial for bone morphogenetic protein 2 to induce new bone formation.  

PubMed

Endochondral ossification is recapitulated during bone morphogenetic protein (BMP)-induced ectopic bone formation. Although BMP and beta-catenin have been investigated in bone development and in mesenchymal cells, how they interact in this process is not clear. We implanted recombinant BMP-2 into the muscle of mice to investigate the effect of beta-catenin signaling on BMP-induced in vivo endochondral bone formation. BMP-2 induced expression of several Wnt ligands and their receptors and also activated beta-catenin-mediated T cell factor-dependent transcriptional activity. An adenovirus expressing Dickkopf-1 (Dkk-1, an inhibitor of canonical Wnt pathway) inhibited beta-catenin signaling and endochondral bone formation. Interestingly, Dkk-1 inhibited both chondrogenesis and osteogenesis. Likewise, mice expressing conditional beta-catenin null alleles also displayed an inhibition of BMP-induced chondrogenesis and osteogenesis. This is in contrast to studies of embryonic skeletogenesis, which demonstrate that beta-catenin is required for osteogenesis but is dispensable for chondrogenesis. These findings suggest that embryonic development pathways are not always recapitulated during post-natal regenerative processes, and the biochemical pathways utilized to regulate cell differentiation may be different. During in vivo ectopic bone formation, BMP-2 induces beta-catenin-mediated signaling through Wnt ligands, and beta-catenin is required for both chondrogenesis and osteogenesis. PMID:17085452

Chen, Yan; Whetstone, Heather C; Youn, Andrew; Nadesan, Puviindran; Chow, Edwin C Y; Lin, Alvin C; Alman, Benjamin A

2007-01-01

109

Osteocyte control of bone remodeling: is sclerostin a key molecular coordinator of the balanced bone resorption-formation cycles?  

PubMed

Osteocytes, entrapped within a newly mineralized bone matrix, possess a unique cellular identity due to a specialized morphology and a molecular signature. These features endow them to serve as a bone response mechanism for mechanical stress in their microenvironment. Sclerostin, a primarily osteocyte product, is widely considered as a mechanotranduction key molecule whose expression is suppressed by mechanical loading, or it is induced by unloading. This review presents a model suggesting that sclerostin is major mediator for integrating mechanical, local, and hormonal signals, sensed by the osteocytes, in controlling the remodeling apparatus. This central role is achieved through interplay between two opposing mechanisms: (1) unloading-induced high sclerostin levels, which antagonize Wnt-canonical-?-catenin signaling in osteocytes and osteoblasts, permitting simultaneously Wnt-noncanonical and/or other pathways in osteocytes and osteoclasts, directed at bone resorption; (2) mechanical loading results in low sclerostin levels, activation of Wnt-canonical signaling, and bone formation. Therefore, adaptive bone remodeling occurring at a distinct bone compartment is orchestrated by altered sclerostin levels, which regulate the expression of the other osteocyte-specific proteins, such as RANKL, OPG, and proteins encoded by "mineralization-related genes" (DMP1, PHEX, and probably FGF23). For example, under specific terms, sclerostin regulates differential RANKL and OPG production, and creates a dynamic RANKL/OPG ratio, leading either to bone formation or resorption. It also controls the expression of PHEX, DMP1, and most likely FGF23, leading to either bone matrix mineralization or its inhibition. Such opposing up- or down-regulation of remodeling phases allows osteocytes to function as an "external unit", ensuring transition from bone resorption to bone formation.Mini Abstract: The osteocyte network plays a central role in directing bone response either to mechanical loading, or to unloading, leading correspondingly to bone formation or resorption. This review shows a key role of the osteocyte-produced sclerostin as a major mediator of the molecular mechanisms involved in the process of adaptive bone remodeling. PMID:25030653

Sapir-Koren, R; Livshits, G

2014-12-01

110

Calcitonin stimulates bone formation when administered prior to initiation of osteogenesis.  

PubMed Central

The influence of calcitonin (CT) on various stages of bone formation was investigated. A demineralized collagenous bone matrix-induced bone forming system in rats was used to temporally segregate chondrogenesis and osteogenesis. Administration of CT (15 Medical Research Council Units [MRCU]) daily) at the initiation of matrix-induced bone formation (BF) resulted in a 76% stimulation of BF as measured by 45Ca incorporation and alkaline phosphatase activity. This increase was due, in part, to a stimulation of cartilage and bone precursor cell proliferation monitored by the rate of [3H]thymidine incorporation and ornithine decarboxylase activity. Chondrogenesis on day 7 as measured by 35SO4 incorporation was increased by 52% with CT treatment. To rule out the possibility of a secondary response due to parathyroid hormone, similar studies were done in parathyroidectomized animals and CT stimulation of BF was still observed. However, when CT injections were started after cartilage formation (day 8) there was no stimulation of BF but a significant decrease in 45Ca incorporation was observed. These results indicate CT has two actions: (a) when CT is administered during the initial phases of bone formation, it increases BF due to a stimulation of proliferation of cartilage and bone precursor cells; and (b) when CT is administered after bone formation has been initiated, subsequent bone formation is suppressed. PMID:7276173

Weiss, R E; Singer, F R; Gorn, A H; Hofer, D P; Nimni, M E

1981-01-01

111

Time since onset of walking predicts tibial bone strength in early childhood.  

PubMed

Bone strength in adulthood is known to be affected by health at birth and early childhood. Habitual bone loading is a primary determinant of bone strength in later childhood and adulthood. However, the effects of physical activity in early childhood (e.g. crawling, standing and walking) on bone strength are unknown. Fifty-three children (twenty-seven males) were included in a longitudinal study in their early infancy. Shortly after birth (0.3±0.3months), details of mass and height were obtained along with a pQCT scan at 20% distal-proximal tibia length. At 14.8±0.5months of age the same data were collected, along with details of age at onset of standing, crawling, supported and unsupported walking. Time since onset of walking unsupported was associated with greater bone mass, cortical bone area, pericortical circumference and polar moment of inertia of both total and cortical bone (all P<0.05). There were no significant associations between other physical activity timepoints and bone measures. Age at onset of walking was not significantly related to mass, length or bone measures at birth. The results suggest that time since attainment of independent walking - representing exposure of the tibia to the large reaction and muscular forces associated with locomotion - is a primary determinant of bone strength in early childhood. This finding raises the possible opportunity of physical activity interventions at young age in paediatric populations associated with low childhood bone strength and late walking (e.g. low birth weight, cerebral palsy and Down's Syndrome, etc.). PMID:25132490

Ireland, Alex; Rittweger, Jörn; Schönau, Eckhard; Lamberg-Allardt, Christel; Viljakainen, Heli

2014-11-01

112

A novel early precursor cell population from rat bone marrow promotes angiogenesis in vitro  

PubMed Central

Background Some studies demonstrated therapeutic angiogenesis attributable to the effects of endothelial progenitor cells (EPC), others have reported disappointing results. This may be due to the fact that EPC populations used in these contradictory studies were selected and defined by highly variable and differing experimental protocols. Indeed, the isolation and reliable characterization of ex vivo differentiated EPC raises considerable problems due to the fact there is no biomarker currently available to specifically identify EPC exclusively. On the other hand traditional differentiation of primary immature bone marrow cells towards the endothelial lineage is a time-consuming process of up to 5 weeks. To circumvent these shortcomings, we herein describe a facile method to isolate and enrich a primary cell population from rat bone marrow, combining differential attachment methodology with cell sorting technology. Results The combination of these techniques enabled us to obtain a pure population of early endothelial precursor cells that show homogenous upregulation of CD31 and VEGF-R2 and that are positive for CD146. These cells exhibited typical sprouting on Matrigel™. Additionally, this population displayed endothelial tube formation when resuspended in Matrigel™ as well as in fibrin glue, demonstrating its functional angiogenic capacity. Moreover, these cells stained positive for DiI-ac-LDL and FITC-UEA, two markers that are commonly considered to stain differentiating EPCs. Based upon these observations in this study we describe a novel and time-saving method for obtaining a pure endothelial precursor cell population as early as 2–3 weeks post isolation that exhibits endothelial abilities in vitro and which still might have retained its early endothelial lineage properties. Conclusion The rapid isolation and the high angiogenic potential of these syngeneic cells might facilitate and accelerate the pre-vascularization of transplanted tissues and organs also in a human setting in the future. PMID:24666638

2014-01-01

113

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

PubMed

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

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

2013-11-01

114

Diabetes-related impairment in bone strength is established early in the life course  

PubMed Central

AIM: To evaluate properties of bone quantity/quality using young non-obese Type 1 (T1D)-diabetic (NOD) prone and syngenic non-diabetic (NOD.scid) mice. METHODS: Quantitative bone assessment of tibia was conducted using dual-energy X-ray absorptiometry (DXA) for the evaluation of body mass, bone mineral content, body fat mass and lean mass. Qualitative assessment was accomplished by three-point breakage for assessment of force to failure and micro-computed tomography for evaluation of trabecular and cortical properties of bone. In addition, fasting blood was evaluated prior to sacrifice at week eleven and fifteen to evaluate and compare glucose homeostasis between the strains of mice. RESULTS: Our findings support a perturbation in the relationship between bone quantity, quality, and subsequently, the association between structure and strength. There were no differences in DXA-assessed body composition (body fat, % fat mass and lean mass) and bone composition (bone mineral content and bone mineral density) between strains. However, relative to NOD.scid, NOD mice had lower trabecular bone volume, relative trabecular bone volume, trabecular number and trabecular total material density (P < 0.05). Conversely, NOD mice had greater cortical total mean volume (P < 0.05). General linear models analysis adjusted for body weight revealed a significant contribution of T1D to bone health as early as 5 wk. CONCLUSION: It is well-established that diabetes is a significant risk factor for increased fractures, although the underlying mechanisms are not fully understood. Investigation of bone parameters encompassing strength and structure early in the life course will facilitate the elucidation of the pathogenesis of impaired bone integrity. PMID:23961325

Casazza, Krista; Hanks, Lynae J; Clines, Gregory A; Tse, Hubert M; Eberhardt, Alan W

2013-01-01

115

Estradiol17? and nutritional status affect calcium balance, scale and bone resorption, and bone formation in rainbow trout, Oncorhynchus mykiss  

Microsoft Academic Search

The effects of estradiol-17? (E2) on bone resorption and formation as well as its effects on scale resorption were investigated in rainbow trout in order\\u000a to elucidate the role of the hormone in calcium mobilization from calcified tissues, and to clarify the importance of scale\\u000a and bone as calcium reserves during sexual maturation. Furthermore, the effects of nutritional status on

Petra Persson; Sigurdur Hilmir Johannsson; Yasuaki Takagi; Björn Thrandur Björnsson

1997-01-01

116

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

SciTech Connect

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.

Miyahara, Tatsuro; Takata, Masakazu; Miyata, Masaki; Nagai, Miyuki; Sugure, Akemi; Kozuka, Hiroshi; Kuze, Shougo (Toyama Medical and Pharmaceutical Univ. (Japan))

1991-08-01

117

Dermal bone in early tetrapods: a palaeophysiological hypothesis of adaptation for terrestrial acidosis  

PubMed Central

The dermal bone sculpture of early, basal tetrapods of the Permo-Carboniferous is unlike the bone surface of any living vertebrate, and its function has long been obscure. Drawing from physiological studies of extant tetrapods, where dermal bone or other calcified tissues aid in regulating acid–base balance relating to hypercapnia (excess blood carbon dioxide) and/or lactate acidosis, we propose a similar function for these sculptured dermal bones in early tetrapods. Unlike the condition in modern reptiles, which experience hypercapnia when submerged in water, these animals would have experienced hypercapnia on land, owing to likely inefficient means of eliminating carbon dioxide. The different patterns of dermal bone sculpture in these tetrapods largely correlates with levels of terrestriality: sculpture is reduced or lost in stem amniotes that likely had the more efficient lung ventilation mode of costal aspiration, and in small-sized stem amphibians that would have been able to use the skin for gas exchange. PMID:22535781

Janis, Christine M.; Devlin, Kelly; Warren, Daniel E.; Witzmann, Florian

2012-01-01

118

A soluble activin type IIA receptor induces bone formation and improves skeletal integrity  

PubMed Central

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-? superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-? signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility. PMID:18460605

Pearsall, R. Scott; Canalis, Ernesto; Cornwall-Brady, Milton; Underwood, Kathryn W.; Haigis, Brendan; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Werner, Eric D.; Glatt, Vaida; Stadmeyer, Lisa; Smith, Deanna; Seehra, Jasbir; Bouxsein, Mary L.

2008-01-01

119

Regulation of bone formation and remodeling by G-protein-coupled receptor 48  

PubMed Central

Summary G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of unknown function. Using a knockout mouse model, we have characterized the essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in mice results in a dramatic delay in osteoblast differentiation and mineralization, but not in chondrocyte proliferation and maturation, during embryonic bone formation. Postnatal bone remodeling is also significantly affected in Gpr48-/- mice, including the kinetic indices of bone formation rate, bone mineral density and osteoid formation, whereas the activity and number of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase staining. Examination of the molecular mechanism of Gpr48 action in bone formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen. Together, our data demonstrate that Gpr48 regulates bone formation and remodeling through the cAMP-PKA-Atf4 signaling pathway. PMID:19605502

Luo, Jian; Zhou, Wei; Zhou, Xin; Li, Dali; Weng, Jinsheng; Yi, Zhengfang; Cho, Sung Gook; Li, Chenghai; Yi, Tingfang; Wu, Xiushan; Li, Xiao-Ying; de Crombrugghe, Benoit; Hook, Magnus; Liu, Mingyao

2009-01-01

120

Regulation of bone formation and remodeling by G-protein-coupled receptor 48.  

PubMed

G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of unknown function. Using a knockout mouse model, we have characterized the essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in mice results in a dramatic delay in osteoblast differentiation and mineralization, but not in chondrocyte proliferation and maturation, during embryonic bone formation. Postnatal bone remodeling is also significantly affected in Gpr48(-/-) mice, including the kinetic indices of bone formation rate, bone mineral density and osteoid formation, whereas the activity and number of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase staining. Examination of the molecular mechanism of Gpr48 action in bone formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen. Together, our data demonstrate that Gpr48 regulates bone formation and remodeling through the cAMP-PKA-Atf4 signaling pathway. PMID:19605502

Luo, Jian; Zhou, Wei; Zhou, Xin; Li, Dali; Weng, Jinsheng; Yi, Zhengfang; Cho, Sung Gook; Li, Chenghai; Yi, Tingfang; Wu, Xiushan; Li, Xiao-Ying; de Crombrugghe, Benoit; Höök, Magnus; Liu, Mingyao

2009-08-01

121

Bone formation in psoriatic arthritis: a report from the GRAPPA 2013 Annual Meeting.  

PubMed

The simultaneous presence of bone erosions and bony spurs (osteophytes, enthesophytes) in the joints of patients with psoriatic arthritis (PsA) suggests that the disease leads to enhanced bone resorption as well as increased bone formation, the latter of which has not been observed in patients with rheumatoid arthritis. At the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members heard an update on the current research into the cytokine signature in PsA and its effects on new bone formation. PMID:24882855

Schett, Georg

2014-06-01

122

Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis  

Microsoft Academic Search

The net amount of bone lost during aging is determined by the difference between the amount of bone removed from the endocortical, trabecular and intracortical components of its endosteal (inner) envelope and formed beneath its periosteal (outer) envelope. Endosteal bone loss is determined by the remodeling rate (number of basic multicellular units, BMUs) and the negative balance (the difference between

Ego Seeman

2003-01-01

123

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

PubMed Central

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

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

124

Chondrocyte ?-Catenin Signaling Regulates Postnatal Bone Remodeling Through Modulation of Osteoclast Formation in a Murine Model  

PubMed Central

Objective To investigate whether ?-catenin signaling in chondrocytes regulates osteoclastogenesis, thereby contributing to postnatal bone growth and bone remodeling. Methods Mice with conditional knockout (cKO) or conditional activation (cAct) of chondrocyte-specific ?-catenin were generated. Changes in bone mass, osteoclast numbers, and osteoblast activity were examined. The mechanisms by which ?-catenin signaling in chondrocytes regulates osteoclast formation were determined. Results The ?-catenin cKO mice developed localized bone loss, whereas cAct mice developed a high bone mass phenotype. Histologic findings suggested that these phenotypes were caused primarily by impaired osteoclast formation, rather than impaired bone formation. Further molecular signaling analyses revealed that ?-catenin signaling controlled this process by regulating the expression of the RANKL and osteoprotegerin (OPG) genes in chondrocytes. Activation of ?-catenin signaling in chondrocytes suppressed Rankl gene transcription through a glucocorticoid receptor–dependent mechanism. The severe bone loss phenotype observed in ?-catenin cKO mice was largely restored by treatment with human recombinant OPG or transgenic overexpression of Opg in chondrocytes. Conclusion ?-catenin signaling in chondrocytes plays a key role in postnatal bone growth and bone remodeling through its regulation of osteoclast formation. PMID:24431282

Wang, Baoli; Jin, Hongting; Zhu, Mei; Li, Jia; Zhao, Lan; Zhang, Yejia; Tang, Dezhi; Xiao, Guozhi; Xing, Lianping; Boyce, Brendan F.; Chen, Di

2014-01-01

125

Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.  

PubMed

Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (P<0.004) post-hibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (P<0.0001) during hibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the seasonal changes in serum IGF-I. Since both PGE(2) and IGF-I are associated with collagenous bone formation, it is possible that seasonal changes in a circulating factor influence IGF-I levels in vivo in bears and PGE(2) release in osteoblastic cells in vitro. The significant decrease in serum leptin following arousal from hibernation may promote bone formation during remobilization, assuming there is a similar decrease in intracerebroventricular leptin. These findings support the idea that seasonal changes in the concentration of circulating molecules help regulate bone formation activity and may be important for preventing disuse osteoporosis in bears. PMID:16621944

Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

2006-05-01

126

Morphologic and radiological observations on the earliest bone marrow formation in human embryos and fetuses.  

PubMed

Morphologic and radiologic studies were undertaken on 26 human embryos and fetuses to determine the stage and site of the earliest bone marrow formation. Up to the 10th week of gestation, primary bone marrow is not present anywhere although the intramembranous ossification occurs in the maxilla and mandible and also in the middle portion of the clavicle. At the 11th week of gestation, X-ray examination showed in two fetuses the bone formation in the clavicle, scapula, maxilla, mandible, and the diaphysis of the long bones. Serial sections of these fetuses revealed that the primary bone marrow occurs first in the middle portion of the clavicle. From a series of our embryological studies, the concept of the mononuclear phagocyte system which involves the bone-marrow-derived monocytic origin of tissue macrophages, is not accepted, at least, on the origin of Kupffer cells in human fetal livers. PMID:6624441

Enzan, H; Hara, H; Izumi, T; Ohkita, T

1983-05-01

127

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

NASA Technical Reports Server (NTRS)

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.

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

1999-01-01

128

Skeletal Self-Repair: Stress Fracture Healing by Rapid Formation and Densification of Woven Bone  

PubMed Central

Stress fractures of varying severity were created using a rat model of skeletal fatigue loading. Periosteal woven bone formed in proportion to the level of bone damage, resulting in the rapid recovery of whole-bone strength independent of stress fracture severity. Introduction A hard periosteal callus is a hallmark of stress fracture healing. The factors that regulate the formation of this woven bone callus are poorly understood. Our objective was to produce stress fractures of varying severity and to assess the woven bone response and recovery of bone strength. Materials and Methods We used the forelimb compression model to create stress fractures of varying severity in 192 adult rats. Forelimbs were loaded in fatigue until the displacement reached 30, 45, 65 or 85% of fracture. The osteogenic responses of loaded and contralateral control ulnae were assessed 7 and 14 days after loading using pQCT, microCT, mechanical testing, histomorphometry, and Raman spectroscopy. Results Loading stimulated the formation of periosteal woven bone that was maximal near the ulnar mid-shaft and transitioned to lamellar bone away from the mid-shaft. Woven bone area increased in a dose-response manner with increasing fatigue displacement. Whole-bone strength was partially recovered at 7 days and fully recovered at 14 days, regardless of initial stress fracture severity. The density of the woven bone increased by 80% from 7 to 14 days, due in part to a 30% increase in the mineral:collagen ratio of the woven bone tissue. Conclusion Functional healing of a stress fracture, as evidenced by recovery of whole-bone strength, occurred within 2 weeks, regardless of stress fracture severity. Partial recovery of strength in the first week was attributed to the rapid formation of a collar of woven bone that was localized to the site of bone damage and whose size depended on the level of initial damage. Complete recovery of strength in the second week was due to woven bone densification. For the first time we have shown that woven bone formation occurs as a dose-dependent response following damaging mechanical loading of bone. PMID:17576168

Uthgenannt, Brian A.; Kramer, Michael H.; Hwu, Joyce A.; Wopenka, Brigitte; Silva, Matthew J.

2013-01-01

129

FLUORIDE EFFECTS ON BONE FORMATION AND MINERALIZATION ARE INFLUENCED BY GENETICS  

PubMed Central

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

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

130

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

PubMed Central

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone’s compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. PMID:22878153

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

2012-01-01

131

CER1 gene variations associated with bone mineral density, bone markers, and early menopause in postmenopausal women  

PubMed Central

Background Osteoporosis has a multifactorial pathogenesis characterized by a combination of low bone mass and increased fragility. In our study, we focused on the effects of polymorphisms in CER1 and DKK1 genes, recently reported as important susceptibility genes for osteoporosis, on bone mineral density (BMD) and bone markers in osteoporotic women. Our objective was to evaluate the effect of CER1 and DKK1 variations in 607 postmenopausal women. The entire DKK1 gene sequence and five selected CER1 SNPs were amplified and resequenced to assess whether there is a correlation between these genes and BMD, early menopause, and bone turnover markers in osteoporotic patients. Results Osteoporotic women seem to suffer menopause 2 years earlier than the control group. The entire DKK1 gene sequence analysis revealed six variations. There was no correlation between the six DKK1 variations and osteoporosis, in contrast to the five common CER1 variations that were significantly associated with BMD. Additionally, osteoporotic patients with rs3747532 and rs7022304 CER1 variations had significantly higher serum levels of parathyroid hormone and calcitonin and lower serum levels of osteocalcin and IGF-1. Conclusions No significant association between the studied DKK1 variations and osteoporosis was found, while CER1 variations seem to play a significant role in the determination of osteoporosis and a potential predictive role, combined with bone markers, in postmenopausal osteoporotic women. PMID:24138842

2013-01-01

132

Load Regulates Bone Formation and Sclerostin Expression through a TGF?-Dependent Mechanism  

PubMed Central

Bone continually adapts to meet changing physical and biological demands. Osteoblasts, osteoclasts, and osteocytes cooperate to integrate these physical and biochemical cues to maintain bone homeostasis. Although TGF? acts on all three of these cell types to maintain bone homeostasis, the extent to which it participates in the adaptation of bone to mechanical load is unknown. Here, we investigated the role of the TGF? pathway in load-induced bone formation and the regulation of Sclerostin, a mechanosensitive antagonist of bone anabolism. We found that mechanical load rapidly represses the net activity of the TGF? pathway in osteocytes, resulting in reduced phosphorylation and activity of key downstream effectors, Smad2 and Smad3. Loss of TGF? sensitivity compromises the anabolic response of bone to mechanical load, demonstrating that the mechanosensitive regulation of TGF? signaling is essential for load-induced bone formation. Furthermore, sensitivity to TGF? is required for the mechanosensitive regulation of Sclerostin, which is induced by TGF? in a Smad3-dependent manner. Together, our results show that physical cues maintain bone homeostasis through the TGF? pathway to regulate Sclerostin expression and the deposition of new bone. PMID:23308287

Nguyen, Daniel; Alliston, Tamara

2013-01-01

133

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

PubMed

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 that 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

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

2008-02-01

134

A Seven Day Continuous Infusion of PTH or PTHrP Suppresses Bone Formation and Uncouples Bone Turnover  

PubMed Central

Human in vivo models of primary hyperparathyroidism (HPT), humoral hypercalcemia of malignancy (HHM) or lactational bone mobilization for more than 48 hours have not been described previously. We therefore developed seven-day continuous infusion models using hPTH(1–34) and hPTHrP(1–36) in healthy human adult volunteers. Study subjects developed sustained mild increases in serum calcium (10.0 mg/dl), with marked suppression of endogenous PTH(1–84). The maximal tolerated infused doses over a seven-day period (2 and 4 pmol/kg/hr, for PTH and PTHrP, respectively) were far lower than in prior, briefer human studies (8–28 pmol/kg/hr). In contrast to prior reports using higher PTH and PTHrP doses, both 1,25(OH)2D and TmP/GFR remained unaltered with these low doses, despite achievement of hypercalcemia and hypercalciuria. As expected, bone resorption increased rapidly, and reversed promptly with cessation of the infusion. However, in contrast to events in primary HPT, bone formation was suppressed by 30–40% for the seven days of the infusions. With cessation of PTH and PTHrP infusion, bone formation markers abruptly rebounded upward, confirming that bone formation is suppressed by continuous PTH or PTHrP infusion. These studies demonstrate that continuous exposure of the human skeleton to PTH or PTHrP in vivo recruits and activates the bone resorption program, but causes sustained arrest in the osteoblast maturation program. These events would most closely mimic and model events in HHM. Although not a perfect model for lactation, the increase in resorption and the rebound increase in formation with cessation of the infusions is reminiscent of the maternal skeletal calcium mobilization and reversal that occur following lactation. The findings also highlight similarities and differences between the model and HPT. PMID:21544866

Horwitz, Mara J.; Tedesco, Mary Beth; Sereika, Susan M.; Prebehala, Linda; Gundberg, Caren M.; Hollis, Bruce W.; Bisello, Alessandro; Garcia-Ocana, Adolfo; Carneiro, Raquel M.; Stewart, Andrew F.

2011-01-01

135

Platelet concentration and its effect on bone formation in calvarial defects: An experimental study in rabbits  

Microsoft Academic Search

Statement of problem. The use of the platelet concentration technique is widespread in dental implant surgery. However, its effect or mechanism is not clearly understood. Purpose. This study introduced an animal model for the platelet concentration technique and evaluated its effect on bone formation with natural cancellous bovine bone mineral. Material and methods. Adult New Zealand white rabbits were used

Eun-Seok Kim; Eun-Jin Park; Pill-Hoon Choung

2001-01-01

136

Induction of bone formation by activated monocytes / macrophages depends on Oncostatin M signaling  

E-print Network

) activation by lipopolysaccharide or endogenous ligands, OSM was produced in classically activated induced by monocytes/macrophages and TLRs activation: IL-6 and Leukemia inhibitory factor. We propose and TLR ligands stimulates bone formation that is largely uncoupled from bone resorption and is thus

Boyer, Edmond

137

MESENCHYMAL STEM CELLS AND THEIR PROGENY: DEVELOPMENTAL PARADIGMS GOVERNING OSTEOBLAST DIFFERENTIATION & BONE FORMATION  

Microsoft Academic Search

1 . We will provide insights into the developmental paradigms governing osteoblast differentiation and bone formation from cellular and molecular analyses of developing bone colonies in vitro. METHODS: Cells were isolated from 21 day Wistar rat calvariae, plated at different densities and cultured for up to 3-4 weeks in differentiation medium (?MEM, with antibiotics, 10% FBS, 50 ?g\\/ml ascorbic acid,

Jane E. Aubin; Shulin Zhang; Soshi Uchida

138

Star formation in the early universe  

NASA Astrophysics Data System (ADS)

We investigate the formation of the first stars in the universe. In the context of hierarchical models of structure formation, these Population III stars are expected to form in high or peaks of mass ˜106 M? , collapsing at redshifts ?20-30. We present an exploratory survey, based on numerical simulations using the SPH method. The main results are: (1) Just before the onset of gravitational instability, the primordial gas attains a characteristic temperature of a few 100 K, and a density of 103-104cm-3, with corresponding Jeans mass MJ of ˜10 3 M? . These characteristic values have robust explanation in the microphysics of H2 cooling, related to the minimum temperature that can be reached with the H2 coolant, and to the critical density at which the transition takes place between levels being populated according to NLTE, and according to LTE. The gas fragments into clumps with initial masses close to MJ. This result is remarkably insensitive to the initial conditions, and suggests that the first stars might have been quite massive. (2) The later evolutionary stages, during which the clumps grow in mass due to accretion and merging with other clumps, are quite sensitive to the initial conditions. The key process in building up very massive clumps, with masses up to a few times 104 M? , is merging. (3) We follow the collapse of a clump up to central densities of ˜1014cm-3. Three-body reactions are very efficient in converting the hydrogen into fully molecular form. A central core of ˜102 M? is in a state of free-fall, leaving behind an extended envelope with an isothermal profile. No further subfragmentation is seen. (4) We calculate the generic spectral signature of a population of massive stars at high redshifts. The production rate of ionizing radiation per stellar mass by stars more massive than ˜100 M? is larger by ˜1 order of magnitude for hydrogen and He I, and by ˜2 orders of magnitude for He II, than the emission from a Salpeter IMF.

Bromm, Volker

139

Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.  

PubMed

A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU?+?PEMF groups. The HU?+?PEMF group was subjected to daily 2-hour PEMF exposure at 15?Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, ?-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities, and imply that PEMF might become a potential biophysical treatment modality for disuse osteoporosis. © 2014 American Society for Bone and Mineral Research. PMID:24753111

Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Li, Feijiang; Xu, Qiaoling; Xie, Kangning; Tang, Chi; Liu, Juan; Guo, Wei; Wu, Xiaoming; Jiang, Maogang; Luo, Erping

2014-10-01

140

Skeletal Repair by in Situ Formation of the Mineral Phase of Bone  

Microsoft Academic Search

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength

Brent R. Constantz; Ira C. Ison; Mark T. Fulmer; Robert D. Poser; Susanne T. Smith; Michelle Vanwagoner; John Ross; Steven A. Goldstein; Jesse B. Jupiter; Daniel I. Rosenthal

1995-01-01

141

Effects of cadmium on bone : an in VIVO model for the early response.  

SciTech Connect

Cadmium (Cd) exposure induces bone resorption in vitro and in vivo that can lead to low bone mass and increased incidence of fracture. We have developed an animal model for following the early skeletal response to Cd. A low-calcium (but not calcium-deficient) diet is used to increase gastrointestinal absorption of calcium so that the endogenous fecal calcium excretion is essentially the total fecal calcium excretion. The bone response is followed by quantitation of stable fecal calcium and does not require a radioactive label. After mice were adjusted to a low-calcium diet, Cd was administered by a single gavage and fecal calcium was monitored to determine the magnitude of the calcium release from bone. Fecal calcium excretion ({micro}g Ca/hr; mean {+-} SE) remained at the background level for 8 hr (13.6 {+-} 1.8,n= 18) but increased during the 8- to 24-hr and 24- to 56-hr collection periods (43.8 {+-} 6.8,n= 12; 50.75 {+-} 3.7,n= 6, respectively). The bone response was transient and dropped to nearly background levels during the 56- to 104-hr collection period. Blood calcium levels were normal throughout the time course. Bone resorption occurred at Cd levels of 7.9 {+-} 0.7 {micro}g/liter blood (mean {+-} SE,n= 6), which is in the range of occupational exposure levels. The transient nature of the bone response contrasted to the slow but continuing rise observed in blood Cd levels. These results suggest that a threshold level of Cd is required for a bone response but that chronic levels of Cd in blood do not necessarily indicate the occurrence of continuous active bone resorption. This model can be used to probe early gene changes (prior to the bone response) that may be occurring in response to Cd exposure.

Wilson, A. K.; Bhattacharyya, M. H.; Center for Mechanistic Biology and Biotechnology

1997-01-01

142

Suppression of Inflammation and Effects on New Bone Formation in Ankylosing Spondylitis  

MedlinePLUS

... been shown to prevent new bone formation." Meaning, TNF-a Inhibitor / biologic class medications have not been ... and they are not in an advanced stage, TNF-a inhibitors may be much more effective in ...

143

Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells  

PubMed Central

Summary We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKOob) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKOob mice are thinner, with increased brittleness. Osteoblast activity is reduced as reflected in a reduced bone formation rate and failure to differentiate to a mature mineralizing stage. Bmp2 in osteoblasts also indirectly controls angiogenesis in the periosteum and bone marrow. VegfA production is reduced in Bmp2-cKOob osteoblasts. Deletion of Bmp2 in osteoblasts also leads to defective mesenchymal stem cells (MSCs), which correlates with the reduced microvascular bed in the periosteum and trabecular bones. Expression of several MSC marker genes (?-SMA, CD146 and Angiopoietin-1) in vivo, in vitro CFU assays and deletion of Bmp2 in vitro in ?-SMA+ MSCs support our conclusions. Critical roles of Bmp2 in osteoblasts and MSCs are a vital link between bone formation, vascularization and mesenchymal stem cells. PMID:23843612

Yang, Wuchen; Guo, Dayong; Harris, Marie A.; Cui, Yong; Gluhak-Heinrich, Jelica; Wu, Junjie; Chen, Xiao-Dong; Skinner, Charles; Nyman, Jeffry S.; Edwards, James R.; Mundy, Gregory R.; Lichtler, Alex; Kream, Barbara E.; Rowe, David W.; Kalajzic, Ivo; David, Val; Quarles, Darryl L.; Villareal, Demetri; Scott, Greg; Ray, Manas; Liu, S.; Martin, James F.; Mishina, Yuji; Harris, Stephen E.

2013-01-01

144

Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density  

PubMed Central

Background and purpose The remodeling of morselized bone grafts in revision surgery can be enhanced by an anabolic substance such as a bone morphogenetic protein (BMP). On the other hand, BMPs boost catabolism and might cause a premature resorption, both of the graft and of the new-formed bone. Bisphosphonates inactivate osteoclasts and can be used to control the resorption. We studied a combination of both drugs as a local admix to a cancellous allograft. Methods Cancellous bone allografts were harvested and freeze-dried. Either saline, BMP-7, the bisphosphonate zoledronate, or a combination of BMP-7 and zoledronate were added in solution. The grafts were placed in bone conduction chambers and implanted in the proximal tibia of 34 rats. The grafts were harvested after 6 weeks and evaluated by histomorphometry. Results Bone volume/total volume (BV/TV) was 50% in the grafts treated with the combination of BMP-7 and zoledronate and 16% in the saline controls (p < 0.001). In the zoledronate group BV/TV was 56%, and in the BMP group it was 14%. The ingrowth distance of new bone into the graft was 3.5 mm for the combination of BMP-7 and zoledronate and 2.6 mm in the saline control (p = 0.002). The net amount of retained remodeled bone was more than 4 times higher when BMP-7 and zoledronate were combined than in the controls. Interpretation An anabolic drug like BMP-7 can be combined with an anti-catabolic bisphosphonate as local bone graft adjunct, and the combination increases the amount of remaining bone after remodeling is complete. PMID:21434769

2011-01-01

145

Overexpression of H1 Calponin in Osteoblast Lineage Cells Leads to a Decrease in Bone Mass by Disrupting Osteoblast Function and Promoting Osteoclast Formation  

PubMed Central

H1 calponin (CNN1) is known as a smooth muscle-specific, actin-binding protein which regulates smooth muscle contractive activity. Although previous studies have shown that CNN1 has effect on bone, the mechanism is not well defined. To investigate the role of CNN1 in maintaining bone homeostasis, we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast-specific 3.6-kb Col1a1 promoter. Col1a1-Cnn1 transgenic mice showed delayed bone formation at embryonic stage and decreased bone mass at adult stage. Morphology analyses showed reduced trabecular number, thickness and defects in bone formation. The proliferation and migration of osteoblasts were decreased in Col1a1-Cnn1 mice due to alterations in cytoskeleton. The early osteoblast differentiation of Col1a1-Cnn1 mice was increased, but the late stage differentiation and mineralization of osteoblasts derived from Col1a1-Cnn1 mice were significantly decreased. In addition to impaired bone formation, the decreased bone mass was also associated with enhanced osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) staining revealed increased osteoclast numbers in tibias of 2-month-old Col1a1-Cnn1 mice, and increased numbers of osteoclasts co-cultured with Col1a1-Cnn1 osteoblasts. The ratio of RANKL to OPG was significantly increased in Col1a1-Cnn1 osteoblasts. These findings reveal a novel function of CNN1 in maintaining bone homeostasis by coupling bone formation to bone resorption. PMID:23044709

Su, Nan; Chen, Maomao; Chen, Siyu; Li, Can; Xie, Yangli; Zhu, Ying; Zhang, Yaozong; Zhao, Ling; He, Qifen; Du, Xiaolan; Chen, Di; Chen, Lin

2013-01-01

146

Platelets guide the formation of early metastatic niches  

PubMed Central

During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments (“niches”) that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form “early metastatic niches.” Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis. PMID:25024172

Labelle, Myriam; Begum, Shahinoor; Hynes, Richard O.

2014-01-01

147

Tamoxifen Attenuates Glucocorticoid Actions on Bone Formation in Vitro  

Microsoft Academic Search

Tamoxifen is a synthetic estrogen analog which may regulate os- teogenesis in vivo by virtue of its antiglucocorticoid properties. We have examined tamoxifen regulation of glucocorticoid-induced osteo- genesis in two different in vitro bone systems: the chicken periosteal osteogenesis model (CPO) and rat bone marrow stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma cell line, ROS 17\\/2.8.

B. Sukhu; B. ROTENBERG; C. BINKERT; H. KOHNO; R. ZOHAR; C. A. G. MCCULLOCH; H. C. TENENBAUM

1997-01-01

148

Insulin and new bone formation in diffuse idiopathic skeletal hyperostosis  

Microsoft Academic Search

Summary  \\u000aThe tendency of patients with DISH towards obesity or an adult onset of diabetes has been reflected in marked hyperinsulinaemia following glucose challenge. It is hypothesized that insulin at prolonged and high physiologic levels promotes new bone growth, particularly in the entheseal regions. These areas are also subject to various mechanical forces. The resulting new bone produces the radiological

G. O. Littlejohn

1985-01-01

149

Early response of bone marrow osteoprogenitors to skeletal unloading and sclerostin antibody.  

PubMed

Sclerostin functions as an antagonist to Wnt signaling and inhibits bone-forming activity. We studied the effects of skeletal unloading and treatment with sclerostin antibody (Scl-Ab) on mesenchymal stem cell, osteoprogenitor and osteoclast precursor pools, and their relationship to bone formation and resorption. Male C57BL/6 mice (5-months-old) were hind limb unloaded for 1 week or allowed normal ambulation and treated with Scl-Ab (25 mg/kg, s.c. injections on days 1 and 4) or placebo. Unloading decreased the serum concentration of bone formation marker P1NP (-35 %), number of colony-forming units (CFU) (-38 %), alkaline phosphatase-positive CFUs (CFU-AP+) (-51 %), and calcified nodules (-35 %); and resulted in a fourfold increase in the number of osteoclast precursors. The effects of Scl-Ab treatment on unloaded and normally loaded mice were nearly identical; Scl-Ab increased serum P1NP and the number of CFU, CFU-AP+, and calcified nodules in ex vivo cultures; and increased osteoblast and bone mineralizing surfaces in vivo. Although the marrow-derived osteoclast precursor population increased with Scl-Ab, the bone osteoclast surface did not change, and the serum concentration of osteoclast activity marker TRACP5b decreased. Our data suggest that short-term Scl-Ab treatment can prevent the decrease in osteoprogenitor population associated with skeletal unloading and increase osteoblast surface and bone mineralizing surface in unloaded animals. The anabolic effects of Scl-Ab treatment on bone are preserved during skeletal unloading. These findings suggest that Scl-Ab treatment can both increase bone formation and decrease bone resorption, and provide a new means for prevention and treatment of disuse osteoporosis. PMID:22644321

Shahnazari, Mohammad; Wronski, Thomas; Chu, Vivian; Williams, Alyssa; Leeper, Alicia; Stolina, Marina; Ke, Hua Zhu; Halloran, Bernard

2012-07-01

150

Effects of sodium acetate on rat bone-nodule formation and mineralization in vitro.  

PubMed

Sodium acetate reportedly promotes bone atrophy by inducing resorption and inhibiting osteoprogenitor-cell proliferation, but little is known about its effects on bone-matrix deposition and mineralization by a population containing osteoprogenitor cells. The objective here was to assess the effects of 1-20 mM sodium acetate on the proliferation and differentiation of these cells and their resultant bone-nodule formation and mineralization in an in vitro assay. Exposure to 10 mM sodium acetate had no effect on cellular proliferation but significantly increased the production and mineralization of bone nodules (p < 0.01), suggesting that it affected osteoprogenitor differentiation and subsequent metabolism. However, 10 mM acetate did not increase net bone mass. Dilutions of 1-5 and 20 mM inhibited cellular proliferation and resultant bone-nodule formation and mineralization, significantly reducing the percentage bone area as compared to controls (p < 0.001). These data suggest that 1-5 and 20 mM sodium acetate significantly inhibit bone deposition, whereas 10 mM has no effects, which could contribute to iatrogenic metabolic bone disease in patients receiving either renal dialysis or total parenteral nutrition. PMID:9783827

Visconti, L A; Yen, E H; Johnson, R B

1998-09-01

151

Influence of early zoledronic Acid administration on bone marrow fat in ovariectomized rats.  

PubMed

Although the primary target cell of bisphosphonates is the osteoclast, increasing attention is being given to other effector cells influenced by bisphosphonates, such as osteoblasts and marrow adipocytes. Early zoledronic acid (ZA) treatment to ovariectomized (OVX) rats has been found to fully preserve bone microarchitecture over time. However, little is known regarding the influence of ZA on marrow adipogenesis. The purpose of this study was to monitor the ability of early administration of ZA in restoring marrow adiposity in an estrogen-deficient rat model. Thirty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX + vehicle, and OVX + ZA groups (n=10/group). Dual-energy x-ray absorptiometry and water/fat magnetic resonance imaging were performed at baseline, 6 weeks, and 12 weeks after treatment to assess bone mineral density and marrow fat fraction. Serum biochemical markers, bone remodeling, and marrow adipocyte parameters were analyzed using biochemistry, histomorphometry, and histopathology, respectively. The expression levels of osteoblast, adipocyte, and osteoclast-related genes in bone marrow were assessed using RT-PCR. The OVX rats showed marked bone loss, first detected at 12 weeks, but estrogen deficiency resulted in a remarked increase in marrow fat fraction, first detected at 6 weeks compared with the SHAM rats (all P < .001). Similarly, the OVX rats had a substantially larger percent adipocyte area (+163.0%), mean diameter (+29.5%), and higher density (+57.3%) relative to the SHAM rats. Bone histomorphometry, levels of osteoclast-related gene expression, and a serum resorption marker confirmed that ZA significantly suppressed bone resorption activities. Furthermore, ZA treatment returned adipocyte-related gene expression and marrow adipocyte parameters toward SHAM levels. These data suggest that a single dose of early ZA treatment acts to reverse marrow adipogenesis occurring during estrogen deficiency, which may contribute to its capacity to reduce bone loss. PMID:25243855

Li, Guan-Wu; Xu, Zheng; Chang, Shi-Xin; Zhou, Lei; Wang, Xiao-Yan; Nian, Hua; Shi, Xiao

2014-12-01

152

Early results of secondary bone grafts in 106 alveolar clefts.  

PubMed

Eighty-three patients with cleft lip and cleft palate were treated by secondary bone grafts to the 106 alveolar clefts. In 98% of the alveolar clefts, the graft was successful and the oronasal fistula was closed. There were only occasional other complications, all but one of which were minor and did not affect the final result. Morbidity was low. Compared with older patients, the pre-teen group of patients not only had no complications of consequence but experienced less morbidity. The 100% success rate and the lower morbidity in the pre-teen group of patients thus favor operating on patients at the younger age. PMID:6339697

Hall, H D; Posnick, J C

1983-05-01

153

Bones, breasts, and bisphosphonates: rationale for the use of zoledronic acid in advanced and early breast cancer.  

PubMed

Bisphosphonates inhibit osteoclast-mediated bone resorption, thereby inhibiting the release of growth factors necessary to promote cancer cell growth, differentiation, and tumor formation in bone. These agents have demonstrated efficacy for delaying the onset and reducing the incidence of skeletal-related events in the advanced breast cancer setting, and have been shown to prevent cancer therapy-induced bone loss in the early breast cancer setting. Emerging clinical data indicate that the role of bisphosphonates in advanced and early breast cancer is evolving. Retrospective analyses and recent clinical trial data show that zoledronic acid may improve outcomes in some patients with breast cancer. Data from ABCSG-12 and ZO-FAST suggest that zoledronic acid may improve disease-free survival in the adjuvant breast cancer setting in postmenopausal women or women with endocrine therapy-induced menopause, and recent data from a predefined subset of the AZURE trial added to the anticancer story. However, the overall negative AZURE trial also raises questions about the role of bisphosphonates as an anticancer agent in patients with breast cancer. Overall, these data suggest that the addition of zoledronic acid to established anticancer regimens may have potential anticancer benefits in specific patient populations, although more studies are required to define its role. PMID:24367171

Lipton, Allan

2011-01-01

154

Non-invasive monitoring of BMP2 retention and bone formation in composites for bone tissue engineering using SPECT\\/CT and scintillation probes  

Microsoft Academic Search

Non-invasive imaging can provide essential information for the optimization of new drug delivery-based bone regeneration strategies to repair damaged or impaired bone tissue. This study investigates the applicability of nuclear medicine and radiological techniques to monitor growth factor retention profiles and subsequent effects on bone formation. Recombinant human bone morphogenetic protein-2 (BMP-2, 6.5 ?g\\/scaffold) was incorporated into a sustained release vehicle

Diederik H. R. Kempen; Michael J. Yaszemski; Andras Heijink; Theresa E. Hefferan; Laura B. Creemers; Jason Britson; Avudaiappan Maran; Kelly L. Classic; Wouter J. A. Dhert; Lichun Lu

2009-01-01

155

Micromotion-induced strain fields influence early stages of repair at bone-implant interfaces  

PubMed Central

Implant loading can create micromotion at the bone-implant interface. The interfacial strain associated with implant micromotion could contribute to regulating the tissue healing response. Excessive micromotion can lead to fibrous encapsulation and implant loosening. Our objective was to characterize the influence of interfacial strain on bone regeneration around implants in mouse tibiae. A micromotion system was used to create strain under conditions of (1) no initial contact between implant and bone, and (2) a direct bone-implant contact. Pin- and screw-shaped implants were subjected to displacements of 150 ?m or 300 ?m, 60 cycles/day, for 7 days. Pin-shaped implants placed in 5 animals were subjected to 3 sessions of 150 ?m displacement per day, with 60 cycles per session. Control implants in both types of interfaces were stabilized throughout the healing period. Experimental strain analyses, microtomography, image-based displacement mapping, and finite element simulations were used to characterize interfacial strain fields. Calcified tissue sections were prepared and stained with Goldner to evaluate tissue reaction in higher and lower strain regions. In stable implants, bone formation occurred consistently around the implants. In implants subjected to micromotion, bone regeneration was disrupted in areas of high strain concentrations (e.g. > 30%), whereas lower strain values were permissive of bone formation. Increasing implant displacement or number of cycles per day also changed the strain distribution and disturbed bone healing. These results indicate that not only implant micromotion but also the associated interfacial strain field contributes to regulating the interfacial mechanobiology at healing bone-implant interfaces. PMID:23337705

Wazen, Rima M.; Currey, Jennifer A.; Guo, Hongqiang; Brunski, John B.; Helms, Jill A.; Nanci, Antonio

2013-01-01

156

Early Cretaceous Lizards from the Okurodani Formation of Japan  

Microsoft Academic Search

The Early Cretaceous Okurodani Formation of Gifu Prefecture, Central Honshu, Japan, is yielding an assemblage of small freshwater and terrestrial vertebrates which represent some of the oldest specimens of their kind from Japan. Although rare, at least two types of lizards-probably more-have been recovered. The most common form, described here under the name Sakurasaurus shokawensis nov. gen. et ep., is

Makoto Manabe

1999-01-01

157

Early Family Formation Among White, Black, and Mexican American Women  

Microsoft Academic Search

Using data from Waves I and III of Add Health, this study examines early family formation among 6,144 White, Black, and Mexican American women. Drawing on cultural and structural perspectives, models of the first and second family transitions (cohabitation, marriage, or childbearing) are estimated using discrete-time multinomial logistic regression. Complex differences by race and ethnicity and generation are partially explained

Nancy S. Landale; Robert Schoen; Kimberly Daniels

2010-01-01

158

Early Family Formation among White, Black, and Mexican American Women  

ERIC Educational Resources Information Center

Using data from Waves I and III of Add Health, this study examines early family formation among 6,144 White, Black, and Mexican American women. Drawing on cultural and structural perspectives, models of the first and second family transitions (cohabitation, marriage, or childbearing) are estimated using discrete-time multinomial logistic…

Landale, Nancy S.; Schoen, Robert; Daniels, Kimberly

2010-01-01

159

Searching early bone metastasis on plain radiography by using digital imaging processing  

SciTech Connect

Some authors mention that it is not possible to detect early bone metastasis on plain radiography. In this work we use digital imaging processing to analyze three radiographs taken from a patient with bone metastasis discomfort on the right shoulder. The time period among the first and second radiography was approximately one month and between the first and the third one year. This procedure is a first approach in order to know if in this particular case it was possible to detect an early bone metastasis. The obtained results suggest that by carrying out a digital processing is possible to detect the metastasis since the radiography contains the information although visually it is not possible to observe it.

Jaramillo-Nunez, A.; Perez-Meza, M. [Instituto Nacional de Astrofisica, Optica y Electronica, Apdo. Postal 51 y 216, Pue. (Mexico); Universidad de la Sierra Sur, C. P. 70800, Miahuatlan, Oax. (Mexico)

2012-10-23

160

Palm Tocotrienol Supplementation Enhanced Bone Formation in Oestrogen-Deficient Rats  

PubMed Central

Postmenopausal osteoporosis is the commonest cause of osteoporosis. It is associated with increased free radical activity induced by the oestrogen-deficient state. Therefore, supplementation with palm-oil-derived tocotrienols, a potent antioxidant, should be able to prevent this bone loss. Our earlier studies have shown that tocotrienol was able to prevent and even reverse osteoporosis due to various factors, including oestrogen deficiency. In this study we compared the effects of supplementation with palm tocotrienol mixture or calcium on bone biomarkers and bone formation rate in ovariectomised (oestrogen-deficient) female rats. Our results showed that palm tocotrienols significantly increased bone formation in oestrogen-deficient rats, seen by increased double-labeled surface (dLS/Bs), reduced single-labeled surface (sLS/BS), increased mineralizing surface (MS/BS), increased mineral apposition rate (MAR), and an overall increase in bone formation rate (BFR/BS). These effects were not seen in the group supplemented with calcium. However, no significant changes were seen in the serum levels of the bone biomarkers, osteocalcin, and cross-linked C-telopeptide of type I collagen, CTX. In conclusion, palm tocotrienol is more effective than calcium in preventing oestrogen-deficient bone loss. Further studies are needed to determine the potential of tocotrienol as an antiosteoporotic agent. PMID:23150728

Soelaiman, Ima Nirwana; Ming, Wang; Abu Bakar, Roshayati; Hashnan, Nursyahrina Atiqah; Mohd Ali, Hanif; Mohamed, Norazlina; Muhammad, Norliza; Shuid, Ahmad Nazrun

2012-01-01

161

Mechanical Load Increases in Bone Formation via a Sclerostin-Independent Pathway.  

PubMed

Sclerostin, encoded by the Sost gene, is an important negative regulator of bone formation that has been proposed to have a key role in regulating the response to mechanical loading. To investigate the effect of long-term Sclerostin deficiency on mechanotransduction in bone, we performed experiments on unloaded or loaded tibiae of 10 week old female Sost-/- and wild type mice. Unloading was induced via 0.5U botulinum toxin (BTX) injections into the right quadriceps and calf muscles, causing muscle paralysis and limb disuse. On a separate group of mice, increased loading was performed on the left tibiae through unilateral cyclic axial compression of equivalent strains (+1200?µe) at 1200 cycles/day, 5 days/week. Another cohort of mice receiving equivalent loads (-9.0?N) also were assessed. Contralateral tibiae served as normal load controls. Loaded/unloaded and normal load tibiae were assessed at day 14 for bone volume (BV) and formation changes. Loss of BV was seen in the unloaded tibiae of wild type mice, but BV was not different between normal load and unloaded Sost-/- tibiae. An increase in BV was seen in the loaded tibiae of wild type and Sost-/- mice over their normal load controls. The increased BV was associated with significantly increased mid-shaft periosteal mineralizing surface/bone surface (MS/BS), mineral apposition rate (MAR), and bone formation rate/bone surface (BFR/BS), and endosteal MAR and BFR/BS. Notably, loading induced a greater increase in periosteal MAR and BFR/BS in Sost-/- mice than in wild type controls. Thus, long-term Sclerostin deficiency inhibits the bone loss normally induced with decreased mechanical load, but it can augment the increase in bone formation with increased load. © 2014 American Society for Bone and Mineral Research. PMID:24821585

Morse, A; McDonald, Mm; Kelly, Nh; Melville, Km; Schindeler, A; Kramer, I; Kneissel, M; van der Meulen, McH; Little, Dg

2014-11-01

162

Identification of Mechanosensitive Genes during Embryonic Bone Formation  

Microsoft Academic Search

Although it is known that mechanical forces are needed for normal bone development, the current understanding of how biophysical stimuli are interpreted by and integrated with genetic regulatory mechanisms is limited. Mechanical forces are thought to be mediated in cells by ''mechanosensitive'' genes, but it is a challenge to demonstrate that the genetic regulation of the biological system is dependant

Niamh C. Nowlan; Patrick J. Prendergast; Paula Murphy

2008-01-01

163

Exercise Effects on Fitness and Bone Mineral Density in Early Postmenopausal Women: 1-Year EFOPS Results.  

ERIC Educational Resources Information Center

Investigated the effect of intense exercise training on physical fitness, coronary heart disease, bone mineral density (BMD), and parameters related to quality of life in early postmenopausal women with osteopenia. Data on woman in control and exercise training groups indicated that the intense exercise training program was effective in improving…

Kemmler, Wolfgang; Engelke, Klaus; Lauber, Dirk; Weineck, Juergen; Hensen, Johannes; Kalender, Willi A.

2002-01-01

164

Ectopic Osteoid and Bone Formation by Three Calcium-Phosphate Ceramics in Rats, Rabbits and Dogs  

PubMed Central

Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (?-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model. PMID:25229501

Wang, Liao; Zhang, Bi; Bao, Chongyun; Habibovic, Pamela; Hu, Jing; Zhang, Xingdong

2014-01-01

165

Physical Mechanisms of Pattern Formation in the Early Chick Embryo  

NASA Astrophysics Data System (ADS)

Gastrulation marks a critical step in early embryogenesis when the first recognizable patterns are laid down. Although the genome maintains ultimate responsibility for this pattern formation, it cannot actually control the organization of individual cells. The robustness of embryogenic pattern formation suggests that a few simple, physical mechanisms are unleashed and that self-organization results. We perform numerical simulations of early chick gastrulation using an agent based method in which individual cells interact via a handful of behaviors including adhesivity, secretion and chemotaxis. Through these simulations we have identified certain behaviors as being important for various stages and morphological events. For instance, experimental results on primitive streak formation are best reproduced by a model in which the Kohler's Sickle secretes a chemo repellant for streak tip cells, and cell polarization appears to be important for initiating polonaise motion during streak elongation.

Balter, Ariel; Glazier, James; Zaitlen, Benji; Chaplain, Mark; Weijer, Cornelis

2007-03-01

166

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

E-print Network

Bare Bones Pattern Formation: A Core Regulatory Network in Varying Geometries Reproduces Major-D) and anteroposterior (A-P) axes are determined and how the shape of a growing limb affects skeletal element formation. Hypothetical developmental scenarios reproduce skeletal morphologies with features of fossil limbs. Conclusions

Zhang, Yong-Tao

167

Enhanced Control of In Vivo Bone Formation with Surface Functionalized Alginate Microbeads Incorporating Heparin and Human Bone Morphogenetic Protein-2  

PubMed Central

In this study, we tested the hypothesis that a surface functionalization delivery platform incorporating heparin onto strontium alginate microbeads surfaces would convert this “naive carriers” into “mini-reservoirs” for localized in vivo delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) that will induce functional bone regeneration. In vitro evaluation confirmed that (1) heparin incorporation could immobilize and prolong rhBMP-2 release for approximately 3 weeks; (2) a significant decrease (p<0.01) in rhBMP-2 burst release is attainable depending on initial protein load; and (3) rhBMP-2 released from surface functionalized microbeads retained bioactivity and stimulated higher alkaline phosphatase activity in cultured C2C12 cells when compared with daily administration of fresh bolus rhBMP-2. Subsequently, surface functionalized microbeads were used for in vivo delivery of rhBMP-2 at local sites of posterolateral spinal fusion surgery in rats. The microbeads were loaded into the pores of medical-grade polyepsilone caprolactone-tricalcium phosphate scaffolds before implantation. Results revealed robust bone formation and a biomechanically solid fusion after 6 weeks. When compared with a control group consisting of an equivalent amount of rhBMP-2 that was directly adsorbed onto bare-surfaced microbeads with no heparin, a 5.3-fold increase in bone volume fraction and a 2.6-fold increase in bending stiffness (flexion/extension) were observed. When compared with collagen sponge carriers of rhBMP-2, a 1.5-fold and a 1.3-fold increase in bone volume fraction and bending stiffness were observed, respectively. More importantly, 3D micro-computed tomography images enabled the visualization of a well-contained newly formed bone at ipsilateral implant sites with surface functionalized rhBMP-2 delivery. This was absent with collagen sponge carriers where newly formed bone tissue was poorly contained and crossed over the posterior midline to contralateral implants. These findings are important because of complications with current rhBMP-2 delivery method, including excessive, uncontrolled bone formation. PMID:22894570

Abbah, Sunny Akogwu; Liu, Jing; Goh, James Cho Hong

2013-01-01

168

Id1 Represses Osteoclast-Dependent Transcription and Affects Bone Formation and Hematopoiesis  

PubMed Central

Background The bone-bone marrow interface is an area of the bone marrow microenvironment in which both bone remodeling cells, osteoblasts and osteoclasts, and hematopoietic cells are anatomically juxtaposed. The close proximity of these cells naturally suggests that they interact with one another, but these interactions are just beginning to be characterized. Methodology/Principal Findings An Id1?/? mouse model was used to assess the role of Id1 in the bone marrow microenvironment. Micro-computed tomography and fracture tests showed that Id1?/? mice have reduced bone mass and increased bone fragility, consistent with an osteoporotic phenotype. Osteoclastogenesis and pit formation assays revealed that loss of Id1 increased osteoclast differentiation and resorption activity, both in vivo and in vitro, suggesting a cell autonomous role for Id1 as a negative regulator of osteoclast differentiation. Examination by flow cytometry of the hematopoietic compartment of Id1?/? mice showed an increase in myeloid differentiation. Additionally, we found increased expression of osteoclast genes, TRAP, Oscar, and CTSK in the Id1?/? bone marrow microenvironment. Lastly, transplantation of wild-type bone marrow into Id1?/? mice repressed TRAP, Oscar, and CTSK expression and activity and rescued the hematopoietic and bone phenotype in these mice. Conclusions/Significance In conclusion, we demonstrate an osteoporotic phenotype in Id1?/? mice and a mechanism for Id1 transcriptional control of osteoclast-associated genes. Our results identify Id1 as a principal player responsible for the dynamic cross-talk between bone and bone marrow hematopoietic cells. PMID:19956687

Doty, Stephen; Lederman, Hannah K.; Kaplan, Rosandra N.; Rafii, Shahin; Rivella, Stefano; Lyden, David

2009-01-01

169

Hydroxyapatite coating for titanium fibre mesh scaffold enhances osteoblast activity and bone tissue formation.  

PubMed

This study investigated the bone regeneration properties of titanium fibre mesh as a tissue engineering material. A thin hydroxyapatite (HA) coating on the titanium fibre web was created using the developed molecular precursor method without losing the complex interior structure. HA-coated titanium fibre mesh showed apatite crystal formation in vitro in a human osteoblast culture. Titanium fibre mesh discs with or without a thin HA coating were implanted into rat cranial bone defects, and the animals were killed at 2 and 4 weeks. The in vivo experience revealed that the amount of newly formed bone was significantly higher in the HA-coated titanium fibre mesh than in the non-coated titanium fibre mesh 2 weeks after implantation. These results suggest that thin HA coating enhances osteoblast activity and bone regeneration in the titanium fibre mesh scaffold. Thin HA-coating improved the ability of titanium fibre mesh to act as a bone regeneration scaffold. PMID:22513355

Hirota, Makoto; Hayakawa, Tohru; Yoshinari, Masao; Ametani, Akihiro; Shima, Takaki; Monden, Yuka; Ozawa, Tomomichi; Sato, Mitsunobu; Koyama, Chika; Tamai, Naoto; Iwai, Toshinori; Tohnai, Iwai

2012-10-01

170

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

USGS Publications Warehouse

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.

Modreski, P.J.

2001-01-01

171

Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation.  

PubMed Central

Parathyroid hormone-related peptide (PTHrP) was initially identified as a product of malignant tumors that mediates paraneoplastic hypercalcemia. It is now known that the parathyroid hormone (PTH) and PTHrP genes are evolutionarily related and that the products of these two genes share a common receptor, the PTH/PTHrP receptor. PTHrP and the PTH/PTHrP receptor are widely expressed in both adult and fetal tissues, and recent gene-targeting and disruption experiments have implicated PTHrP as a developmental regulatory molecule. Apparent PTHrP functions include the regulation of endochondral bone development, of hair follicle formation, and of branching morphogenesis in the breast. Herein, we report that overexpression of PTHrP in chondrocytes using the mouse type II collagen promoter induces a novel form of chondrodysplasia characterized by short-limbed dwarfism and a delay in endochondral ossification. This features a delay in chondrocyte differentiation and in bone collar formation and is sufficiently marked that the mice are born with a cartilaginous endochondral skeleton. In addition to the delay, chondrocytes in the transgenic mice initially become hypertrophic at the periphery of the developing long bones rather than in the middle, leading to a seeming reversal in the pattern of chondrocyte differentiation and ossification. By 7 weeks, the delays in chondrocyte differentiation and ossification have largely corrected, leaving foreshortened and misshapen but histologically near-normal bones. These findings confirm a role for PTHrP as an inhibitor of the program of chondrocyte differentiation. PTHrP may function in this regard to maintain the stepwise differentiation of chondrocytes that initiates endochondral ossification in the midsection of endochondral bones early in development and that also permits linear growth at the growth plate later in development. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8816783

Weir, E C; Philbrick, W M; Amling, M; Neff, L A; Baron, R; Broadus, A E

1996-01-01

172

Formation of a calcium phosphate-rich layer on absorbable calcium carbonate bone graft substitutes  

Microsoft Academic Search

The use of natural coral as a bone graft substitute is common in Europe. However, the bone-coral bonding mechanism remains elusive. A rat subcutaneous model was used to demonstrate changes at the surface of resorbable calcium carbonate in the form of natural coral. Histological results indicated in vivo formation of a calcium phosphate (CaP)-rich layer on the surface of the

C. J. Damien; J. L. Ricci; P. Christel; H. Alexander; J.-L. Patat

1994-01-01

173

Evolutionary Sequence for the Early Stages of Massive Star Formation  

NASA Astrophysics Data System (ADS)

This paper reviews recent results in the field of massive star formation in connection with methanol masers. 6.7 and 12.2 GHz methanol masers are used as probes to investigate the early phases of massive star formation and appear as excellent tracers of the youngest massive-star forming regions. An evolutionay sequence for massive star formation is proposed in which methanol masers occur in cold dust condensations, hot molecular cores and hyper compact HII regions, i.e. at the earliest stages of the star-forming process. New millimetre continuum observations using SIMBA are also presented and support our evolutionay scenario for massive star formation. Finally, further work at millimetre wavelengths for continuum and spectral lines using the next generation of ground-based interferometer is discussed.

Minier, V.; Burton, M.; Hill, T.

2002-06-01

174

Formation of engineered bone with adipose stromal cells from buccal fat pad.  

PubMed

A robust method for inducing bone formation from adipose-derived stromal cells (ADSCs) has not been established. Moreover, the efficacy of strong osteogenic inducers including BMP-2 for ADSC-mediated bone engineering remains controversial. Meanwhile, the buccal fat pad (BFP), which is found in the oral cavity as an adipose-encapsulated mass, has been shown to have potential as a new accessible source of ADSCs for oral surgeons. However, to date, there have been no reports that define the practical usefulness of ADSCs from BFP (B-ADSCs) for bone engineering. Here, we report an efficient method of generating bone from B-ADSCs using rhBMP-2. The analyses show that B-ADSCs can differentiate in vitro toward the osteoblastic lineage by the addition of rhBMP-2 to culture medium, regardless of the presence of osteoinductive reagents (OSR), as demonstrated by measurements of ALP activity, in vitro calcification, and osteogenic gene expression. Interestingly, adipogenic genes were clearly detectable only in cultures with rhBMP-2 and OSR. However, in vivo bone formation was most substantial when B-ADSCs cultured in this condition were transplanted. Thus, B-ADSCs reliably formed engineered bone when pre-treated with rhBMP-2 for inducing mature osteoblastic differentiation. This study supports the potential translation for B-ADSC use in the clinical treatment of bone defects. PMID:22538411

Shiraishi, T; Sumita, Y; Wakamastu, Y; Nagai, K; Asahina, I

2012-06-01

175

Exercise-Induced Bone Formation Is Poorly Linked to Local Strain Magnitude in the Sheep Tibia  

PubMed Central

Functional interpretations of limb bone structure frequently assume that diaphyses adjust their shape by adding bone primarily across the plane in which they are habitually loaded in order to minimize loading-induced strains. Here, to test this hypothesis, we characterize the in vivo strain environment of the sheep tibial midshaft during treadmill exercise and examine whether this activity promotes bone formation disproportionately in the direction of loading in diaphyseal regions that experience the highest strains. It is shown that during treadmill exercise, sheep tibiae were bent in an anteroposterior direction, generating maximal tensile and compressive strains on the anterior and posterior shaft surfaces, respectively. Exercise led to significantly increased periosteal bone formation; however, rather than being biased toward areas of maximal strains across the anteroposterior axis, exercise-related osteogenesis occurred primarily around the medial half of the shaft circumference, in both high and low strain regions. Overall, the results of this study demonstrate that loading-induced bone growth is not closely linked to local strain magnitude in every instance. Therefore, caution is necessary when bone shaft shape is used to infer functional loading history in the absence of in vivo data on how bones are loaded and how they actually respond to loading. PMID:24897411

Wallace, Ian J.; Demes, Brigitte; Mongle, Carrie; Pearson, Osbjorn M.; Polk, John D.; Lieberman, Daniel E.

2014-01-01

176

Effects of preparation methods on the bone formation potential of apatite-coated chitosan microspheres.  

PubMed

To investigate the effects of preparation methods on the bone formation potential of apatite-coated chitosan microspheres, coacervate precipitation method and emulsion cross-linking method were chosen to prepare chitosan microspheres, and then apatite coatings were deposited using simulated body fluid. Rat bone marrow-derived mesenchymal stem cells (BMSCs) were seeded on these microspheres. Cell adhesion, proliferation, and differentiation potential were monitored. For in vivo analysis, some cell/microsphere constructs were implanted in the subcutaneous pockets of male Wistar rats. After 3, 6, 12 weeks, the samples were retrieved and stained with hematoxylin and eosin (HE). Some cell/microsphere constructs were implanted in the calvarial defects of rats. Micro-CT and HE analysis were performed to analyze the new bone formation. It was found that BMSCs on apatite-coated emulsion cross-linked microspheres (EM1) exhibited better proliferation and differentiation than cells on apatite-coated coacervate-precipitated microspheres. The in vivo results showed that no bone was observed in ectopic areas. While in calvarial defects, both histological slices and Micro-CT images demonstrated that a substantial amount of new bone was formed in the EM1/BMSCs construct. These data suggest that preparation methods do exert great influence on the in vitro cell behaviors and in vivo orthotopic bone regeneration of apatite-coated chitosan microspheres. Appropriate method should be considered when preparing chitosan microspheres for bone tissue engineering scaffold. PMID:25324120

Xu, Fei; Ding, Huifen; Song, Fangfang; Wang, Jiawei

2014-12-01

177

Determinants of bone and blood lead concentrations in the early postpartum period  

PubMed Central

OBJECTIVE—This study investigated determinants of bone and blood lead concentrations in 430 lactating Mexican women during the early postpartum period and the contribution of bone lead to blood lead.?METHODS—Maternal venous lead was measured at delivery and postpartum, and bone lead concentrations, measured with in vivo K-x ray fluorescence, were measured post partum. Data on environmental exposure, demographic characteristics, and maternal factors related to exposure to lead were collected by questionnaire. Linear regression was used to examine the relations between bone and blood lead, demographics, and environmental exposure variables.?RESULTS—Mean (SD) blood, tibial, and patellar lead concentrations were 9.5 (4.5) µg/dl, 10.2 (10.1) µg Pb/g bone mineral, and 15.2 (15.1) µg Pb/g bone mineral respectively. These values are considerably higher than values for women in the United States. Older age, the cumulative use of lead glazed pottery, and higher proportion of life spent in Mexico City were powerful predictors of higher bone lead concentrations. Use of lead glazed ceramics to cook food in the past week and increased patellar lead concentrations were significant predictors of increased blood lead. Patellar lead concentrations explained one third of the variance accounted for by the final blood lead model. Women in the 90th percentile for patella lead had an untransformed predicted mean blood lead concentration 3.6 µg/dl higher than those in the 10th percentile.?CONCLUSIONS—This study identified the use of lead glazed ceramics as a major source of cumulative exposure to lead, as reflected by bone lead concentrations, as well as current exposure, reflected by blood lead, in Mexico. A higher proportion of life spent in Mexico City, a proxy for exposure to leaded gasoline emissions, was identified as the other major source of cumulative lead exposure. The influence of bone lead on blood lead coupled with the long half life of lead in bone has implications for other populations and suggests that bone stores may pose a threat to women of reproductive age long after exposure has declined.???Keywords: postpartum; blood lead; bone lead PMID:10896960

Brown, M. J.; Hu, H.; Gonzales-Cossio, T.; Peterson, K.; Sanin, L.; Kageyama, M. d.; Palazuelos, E.; Aro, A.; Schnaas, L.; Hernandez-Avila, M.

2000-01-01

178

FAD104, a Regulatory Factor of Adipogenesis, Acts as a Novel Regulator of Calvarial Bone Formation*  

PubMed Central

Osteogenesis is a complex process that is orchestrated by several growth factors, extracellular cues, signaling molecules, and transcriptional factors. Understanding the mechanisms of bone formation is pivotal for clarifying the pathogenesis of bone diseases. Previously, we reported that fad104 (factor for adipocyte differentiation 104), a novel positive regulator of adipocyte differentiation, negatively regulated the differentiation of mouse embryonic fibroblasts into osteocytes. However, the physiological role of fad104 in bone formation has not been elucidated. Here, we clarified the role of fad104 in bone formation in vivo and in vitro. fad104 disruption caused craniosynostosis-like premature ossification of the calvarial bone. Furthermore, analyses using primary calvarial cells revealed that fad104 negatively regulated differentiation and BMP/Smad signaling pathway. FAD104 interacted with Smad1/5/8. The N-terminal region of FAD104, which contains a proline-rich motif, was capable of binding to Smad1/5/8. We demonstrated that down-regulation of Smad1/5/8 phosphorylation by FAD104 is dependent on the N-terminal region of FAD104 and that fad104 functions as a novel negative regulator of BMP/Smad signaling and is required for proper development for calvarial bone. These findings will aid a comprehensive description of the mechanism that controls normal and premature calvarial ossification. PMID:24052261

Kishimoto, Keishi; Nishizuka, Makoto; Katoh, Daiki; Kato, Ayumi; Osada, Shigehiro; Imagawa, Masayoshi

2013-01-01

179

WNT7B Promotes Bone Formation in part through mTORC1  

PubMed Central

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

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

2014-01-01

180

Fibrillin-1 and -2 differentially modulate endogenous TGF-? and BMP bioavailability during bone formation.  

PubMed

Extracellular regulation of signaling by transforming growth factor (TGF)-? family members is emerging as a key aspect of organ formation and tissue remodeling. In this study, we demonstrate that fibrillin-1 and -2, the structural components of extracellular microfibrils, differentially regulate TGF-? and bone morphogenetic protein (BMP) bioavailability in bone. Fibrillin-2-null (Fbn2(-/-)) mice display a low bone mass phenotype that is associated with reduced bone formation in vivo and impaired osteoblast maturation in vitro. This Fbn2(-/-) phenotype is accounted for by improper activation of latent TGF-? that selectively blunts expression of osterix, the transcriptional regulator of osteoblast maturation, and collagen I, the structural template for bone mineralization. Cultured osteoblasts from Fbn1(-/-) mice exhibit improper latent TGF-? activation as well, but mature faster because of increased availability of otherwise matrix-bound BMPs. Additional in vitro evidence excludes a direct role of microfibrils in supporting mineral deposition. Together, these findings identify the extracellular microfibrils as critical regulators of bone formation through the modulation of endogenous TGF-? and BMP signaling. PMID:20855508

Nistala, Harikiran; Lee-Arteaga, Sui; Smaldone, Silvia; Siciliano, Gabriella; Carta, Luca; Ono, Robert N; Sengle, Gerhard; Arteaga-Solis, Emilio; Levasseur, Regis; Ducy, Patricia; Sakai, Lynn Y; Karsenty, Gerard; Ramirez, Francesco

2010-09-20

181

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

PubMed Central

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

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

2013-01-01

182

Is Lipid Profile Associated with Bone Mineral Density and Bone Formation in Subjects with Spinal Cord Injury?  

PubMed Central

Purpose. The association between serum lipids and bone mineral density (BMD) has been investigated previously but, up to now, these relationships have not yet been described in spinal cord injury (SCI). We tried to assess the correlation between serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) and BMD in male subjects with SCI. Methods. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD in femoral neck, trochanter, intertrochanteric zone, and lumbar vertebras. Blood samples were taken to measure serums lipids and bone biomarkers including osteocalcin, cross-linked type I collagen (CTX), and bone alkaline phosphatase (BALP). Partial correlation analysis was used to evaluate the relationships between mentioned measurements after adjustment for weight and age. Results. We found a positive correlation between HDL and femoral neck BMD (P: 0.004, r = 0.33). HDL was negatively correlated with osteocalcin (P: 0.017, r = ?0.31) which was not in consistency with its relationship with BMD. TC and LDL were not related to CTX, BALP and BMD. Conclusion. This study does not support a strong association between serum lipids and BMD in subjects with SCI. Moreover it seems that positive association between HDL and BMD is not mediated through increased bone formation.

Sabour, Hadis; Norouzi Javidan, Abbas; Latifi, Sahar; Hadian, Mohammad Reza; Emami Razavi, Seyed-Hassan; Shidfar, Farzad; Vafa, Mohammad Reza; Aghaei Meybodi, Hamidreza

2014-01-01

183

Formation of early water oceans on rocky planets  

Microsoft Academic Search

Terrestrial planets, with silicate mantles and metallic cores, are likely to obtain water and carbon compounds during accretion.\\u000a Here I examine the conditions that allow early formation of a surface water ocean (simultaneous with cooling to clement surface\\u000a conditions), and the timeline of degassing the planetary interior into the atmosphere. The greatest fraction of a planet’s\\u000a initial volatile budget is

Linda T. Elkins-Tanton

2011-01-01

184

Report on the ''ALMA Early Science Massive Star Formation Workshop''  

NASA Astrophysics Data System (ADS)

With the deadline for ALMA Early Science Cycle 0 proposals fast approaching, a workshop was held for members of the European massive star formation community to discuss ideas for potential ALMA Early Science projects. The workshop began with short summary talks on the ALMA Early Science capabilities, the multi-wavelength large-area survey data available as ALMA source-finder charts and the modelling/analysis tools that are available to help interpret future ALMA data. The rest of the meeting was spent discussing science ideas and proposal strategies. There was general agreement on the main science questions to be addressed, the basic observing strategies required to achieve the goals and the future steps needed to develop the ideas into proposals.

Longmore, S.; Testi, L.; Klaassen, P.

2011-06-01

185

Early Family Formation among White, Black and Mexican American Women  

PubMed Central

Using data from Waves I and III of Add Health, we examine early family formation among 6,144 White, Black, and Mexican American women. Drawing on cultural and structural perspectives, we estimate models of the first and second family transitions (cohabitation, marriage, or childbearing) using discrete time multinomial logistic regression. Complex differences by race/ethnicity and generation are partially explained by differences in attitudes and values in adolescence and family SES; marriage values are especially important in first-generation Mexican women's early entry into marriage. Examination of sequential family transitions sheds light on race/ethnic differences in the meaning and consequences of early cohabitation and pre-union births. PMID:20368754

Landale, Nancy S.; Schoen, Robert; Daniels, Kimberly

2008-01-01

186

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

PubMed Central

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

Ripamonti, Ugo; Ferretti, C; Heliotis, M

2006-01-01

187

Titanium nanotubes activate genes related to bone formation in vitro  

PubMed Central

Background: Titanium is used worldwide to make osseointegrable devices, thanks to its favorable characteristics as mechanical proprieties and biocompatibility, demonstrated by in vivo studies with animal models and clinical trials over a forty-year period. However, the exact genetic effect of the titanium layer on cells is still not well characterized. Materials and Methods: To investigate how titanium nanotubes stimulate osteoblasts differentiation and proliferation, some osteoblast genes (SP7, RUNX2, COL3A1, COL1A1, ALPL, SPP1 and FOSL1) were analyzed by quantitative Real Time RT- PCR. Results: After 15 days, osteoblasts cultivated on titanium naotube showed the up-regulation of bone related genes SP7, ENG, FOSL1 and SPP1 and the down-regulation of RUNX2, COL3A1, COL1A1, and ALPL. After 30 days of treatment, the bone related genes SP7, ENG, FOSL1 and RUNX2 were up-regulated while COL3A1, COL1A1, ALPL and SPP1 were down-regulated. Conclusions: Our results, demonstrates that titanium nanotubes can lead to osteoblast differentiation and extracellular matrix deposition and mineralization in dental pulp stem cells by the activation of osteoblast related genes SPP1, FOSL1 and RUNX2. PMID:23814577

Pozio, Alfonso; Palmieri, Annalisa; Girardi, Ambra; Cura, Francesca; Carinci, Francesco

2012-01-01

188

The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation  

Microsoft Academic Search

We have identified a novel zinc finger-containing transcription factor, called Osterix (Osx), that is specifically expressed in all developing bones. In Osx null mice, no bone formation occurs. In endochondral skeletal elements of Osx null mice, mesenchymal cells, together with osteoclasts and blood vessels, invade the mineralized cartilage matrix. However, the mesenchymal cells do not deposit bone matrix. Similarly, cells

Kazuhisa Nakashima; Xin Zhou; Gary Kunkel; Zhaoping Zhang; Jian Min Deng; Richard R. Behringer; Benoit de Crombrugghe

2002-01-01

189

Advanced Molecular Profiling in Vivo Detects Novel Function of Dickkopf-3 in the Regulation of Bone Formation  

E-print Network

development(1) and fracture healing.(2) Endochondral bone formation is a multistep process that involves to verify and understand the complexity of endochondral bone forma- tion. In a rat fracture model, severalAdvanced Molecular Profiling in Vivo Detects Novel Function of Dickkopf-3 in the Regulation of Bone

Domany, Eytan

190

Sink or swim? Bone density as a mechanism for buoyancy control in early cetaceans.  

PubMed

Previous analyses have shown that secondarily aquatic tetrapods, including whales, exhibit osteological adaptations to life in water as part of their complex buoyancy control systems. These structural specializations of bone span hyperostosis through osteoporosis. The past 15 years of paleontological effort has provided an unprecedented opportunity to examine the osteological transformation of whales as they make their transition to an obligate aquatic lifestyle over a 10-million-year period. It is hypothesized that whales manifest their osteological specialization in the same manner as extant semiaquatic and fully aquatic mammals. This study presents and analysis of the microstructural features of bone in early and late archaic cetaceans, and in a comparative sample of modern terrestrial, semiaquatic, and aquatic mammals. Bone histology was examined from the ribs of 10 fossilized individuals representing five early cetacean families, including Pakicetidae, Ambulocetidae, Protocetidae, Remintonocetidae, and Basilosauridae. Comparisons were then made with rib histology from nine genera of extant mammals including: Odocoileus (deer), Bos (cow), Equus (horse), Canis (dog), Lutra (river otter), Enhydra (sea otter), Choeropsis (pygmy hippo), Trichechus (sea cow), and Delphinus (dolphin). Results show that the transition from terrestrial, to semiaquatic, to obligate aquatic locomotion in archaeocetes involved a radical shift in bone function achieved by means of profound changes at the microstructural level. A surprising finding was that microstructural change predates gross anatomical shift in archaeocetes associated with swimming. Histological analysis shows that high bone density is an aquatic specialization that provides static buoyancy control (ballast) for animals living in shallow water, while low bone density is associated with dynamic buoyancy control for animals living in deep water. Thus, there was a shift from the typical terrestrial form, to osteopetrosis and pachyosteosclerosis, and then to osteoporosis in the first quarter of cetacean evolutionary history. PMID:17516430

Gray, Noel-Marie; Kainec, Kimberly; Madar, Sandra; Tomko, Lucas; Wolfe, Scott

2007-06-01

191

CO2-SO2 clathrate hydrate formation on early Mars  

NASA Astrophysics Data System (ADS)

It is generally agreed that a dense CO2-dominant atmosphere was necessary in order to keep early Mars warm and wet. However, current models have not been able to produce surface temperature higher than the freezing point of water. Most sulfate minerals discovered on Mars are dated no earlier than the Hesperian, despite likely much stronger volcanic activities and more substantial release of sulfur-bearing gases into martian atmosphere during the Noachian. Here we show, using a 1-D radiative-convective-photochemical model, that clathrate formation during the Noachian would have buffered the atmospheric CO2 pressure of early Mars at ˜2 bar and maintained a global average surface temperature ˜230 K. Because clathrates trap SO2 more favorably than CO2, all volcanically outgassed sulfur would have been trapped in Noachian Mars cryosphere, preventing a significant formation of sulfate minerals during the Noachian and inhibiting carbonates from forming at the surface in acidic water resulting from the local melting of the SO2-rich cryosphere. The massive formation of sulfate minerals at the surface of Mars during the Hesperian could be the consequence of a drop of the CO2 pressure below a 2-bar threshold value at the late Noachian-Hesperian transition, which would have released sulfur gases into the atmosphere from both the Noachian sulfur-rich cryosphere and still active Tharsis volcanism. A lower value of the pressure threshold, down to ˜0.5 bar, could have been sufficient to maintain middle and high latitude regions below the clathrate formation temperature during the Noachian and to make the trapping of SO2 in clathrates efficient. Our hypothesis could allow to explain the formation of chaotic terrains and outflow channels, and the occurrence of episodic warm episodes facilitated by the release of SO2 to the atmosphere. These episodes could explain the formation of valley networks and the degradation of impact craters, but remain to be confirmed by further modeling.

Chassefière, Eric; Dartois, Emmanuel; Herri, Jean-Michel; Tian, Feng; Schmidt, Frédéric; Mousis, Olivier; Lakhlifi, Azzedine

2013-04-01

192

Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation  

PubMed Central

Cathepsin K (CTSK) is secreted by osteoclasts to degrade collagen and other matrix proteins during bone resorption. Global deletion of Ctsk in mice decreases bone resorption, leading to osteopetrosis, but also increases the bone formation rate (BFR). To understand how Ctsk deletion increases the BFR, we generated osteoclast- and osteoblast-targeted Ctsk knockout mice using floxed Ctsk alleles. Targeted ablation of Ctsk in hematopoietic cells, or specifically in osteoclasts and cells of the monocyte-osteoclast lineage, resulted in increased bone volume and BFR as well as osteoclast and osteoblast numbers. In contrast, targeted deletion of Ctsk in osteoblasts had no effect on bone resorption or BFR, demonstrating that the increased BFR is osteoclast dependent. Deletion of Ctsk in osteoclasts increased their sphingosine kinase 1 (Sphk1) expression. Conditioned media from Ctsk-deficient osteoclasts, which contained elevated levels of sphingosine-1-phosphate (S1P), increased alkaline phosphatase and mineralized nodules in osteoblast cultures. An S1P1,3 receptor antagonist inhibited these responses. Osteoblasts derived from mice with Ctsk-deficient osteoclasts had an increased RANKL/OPG ratio, providing a positive feedback loop that increased the number of osteoclasts. Our data provide genetic evidence that deletion of CTSK in osteoclasts enhances bone formation in vivo by increasing the generation of osteoclast-derived S1P. PMID:23321671

Lotinun, Sutada; Kiviranta, Riku; Matsubara, Takuma; Alzate, Jorge A.; Neff, Lynn; Lüth, Anja; Koskivirta, Ilpo; Kleuser, Burkhard; Vacher, Jean; Vuorio, Eero; Horne, William C.; Baron, Roland

2013-01-01

193

Coordination of bone morphogenetic protein 2 (BMP2) and aberrant canonical Wnt/?-catenin signaling for heterotopic bone formation in adrenal myelolipoma: A case report  

PubMed Central

The precise mechanism of heterotopic ossification caused by several types of tumours is largely unknown. However, recent studies have indicated that bone morphogenetic protein 2 (BMP2) is closely linked to the Wnt/?-catenin signaling pathway in this rare phenomenon of bone formation. We report a rare case of adrenal myelolipoma (ML) in a 27-year-old woman with heterotopic bone formation. Immunohistochemical findings showed BMP2 expression in the cytoplasm of tumour cells, as well as the matrix adjacent to newly developed bone tissue. In addition, ?-catenin was prominent in the cytoplasm and nuclei of BMP2-positive tumour cells. To the best of our knowledge, this is the first report of adrenal ML showing heterotopic ossification with accelerated expression of both BMP2 and ?-catenin. Our case findings indicate that BMP2 overexpression via aberrant canonical Wnt/?-catenin signaling may contribute to heterotopic bone formation occurring in adrenal ML. PMID:24554972

Mitsui, Yozo; Yasumoto, Hiroaki; Hiraki, Miho; Arichi, Naoko; Ishikawa, Noriyoshi; Harada, Yuji; Maruyama, Riruke; Shiina, Hiroaki

2014-01-01

194

Coordination of bone morphogenetic protein 2 (BMP2) and aberrant canonical Wnt/?-catenin signaling for heterotopic bone formation in adrenal myelolipoma: A case report.  

PubMed

The precise mechanism of heterotopic ossification caused by several types of tumours is largely unknown. However, recent studies have indicated that bone morphogenetic protein 2 (BMP2) is closely linked to the Wnt/?-catenin signaling pathway in this rare phenomenon of bone formation. We report a rare case of adrenal myelolipoma (ML) in a 27-year-old woman with heterotopic bone formation. Immunohistochemical findings showed BMP2 expression in the cytoplasm of tumour cells, as well as the matrix adjacent to newly developed bone tissue. In addition, ?-catenin was prominent in the cytoplasm and nuclei of BMP2-positive tumour cells. To the best of our knowledge, this is the first report of adrenal ML showing heterotopic ossification with accelerated expression of both BMP2 and ?-catenin. Our case findings indicate that BMP2 overexpression via aberrant canonical Wnt/?-catenin signaling may contribute to heterotopic bone formation occurring in adrenal ML. PMID:24554972

Mitsui, Yozo; Yasumoto, Hiroaki; Hiraki, Miho; Arichi, Naoko; Ishikawa, Noriyoshi; Harada, Yuji; Maruyama, Riruke; Shiina, Hiroaki

2014-01-01

195

Bone mineral content in early-postmenopausal and postmenopausal osteoporotic women: comparison of measurement methods  

SciTech Connect

To investigate associations among methods for noninvasive measurement of skeletal bone mass, we studied 40 healthy early postmenopausal women and 68 older postmenopausal women with osteoporosis. Methods included single- and dual-energy quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) of the lumbar spine, single-photon absorptiometry (SPA) of the distal third of the radius, and combined cortical thickness (CCT) of the second metacarpal shaft. Lateral thoracolumbar radiography was performed, and a spinal fracture index was calculated. There was good correlation between QCT and DPA methods in early postmenopausal women and modest correlation in postmenopausal osteoporotic women. Correlations between spinal measurements (QCT or DPA) and appendicular cortical measurements (SPA or CCT) were modest in healthy women and poor in osteoporotic women. Measurements resulting from one method are not predictive of those by another method for the individual patient. The strongest correlation with severity of vertebral fracture is provided by QCT; the weakest, by SPA. There was a high correlation between single- and dual-energy QCT results, indicating that errors due to vertebral fat are not substantial in these postmenopausal women. Single-energy QCT may be adequate and perhaps preferable for assessing postmenopausal women. The measurement of spinal trabecular bone density by QCT discriminates between osteoporotic women and younger healthy women with more sensitivity than measurements of spinal integral bone by DPA or of appendicular cortical bone by SPA or CCT.

Reinbold, W.D.; Genant, H.K.; Reiser, U.J.; Harris, S.T.; Ettinger, B.

1986-08-01

196

Triple red blood cell alloantibody formation after bone-allograft transplantation.  

PubMed

In this case report, we provide evidence for the possibility of red blood cell alloimmunization after bone-allograft transplantation. Here, we present a 13-year-old boy who received a bone allograft due to impending hip-luxation. Five months later he was shown to have developed three different alloantibodies: anti-D, anti-C and anti-E, which were induced by the bone allograft. Red blood cell alloimmunization is a possible adverse event when a patient is exposed to allogenic red blood cells. These antibodies may cause transfusion reactions when incompatible blood is administered. More importantly, these antibodies may cause severe, or even fatal, hemolytic disease of the fetus or newborn, stretching the importance of preventing antibody formation, especially in young women. This case demonstrates the importance of selecting rhesus phenotype compatible bone allografts. PMID:23094701

Prinzen, L; Staal, H M; Rouwette, S J M; Beckers, E A M; ten Broeke, R H M; van Rhijn, L W; Henskens, Y M C

2013-01-01

197

Unique Roles of Phosphorus in Endochondral Bone Formation and Osteocyte Maturation  

PubMed Central

The mechanisms by which inorganic phosphate (Pi) homeostasis controls bone biology are poorly understood. Here we used Dmp1 null mice, a hypophosphatemic rickets/osteomalacia model, combined with a metatarsal organ culture and an application of neutralizing fibroblast growth factor 23 (FGF-23) antibodies to gain insight into the roles of Pi in bone biology. We showed (1) that abnormal bone remodeling in Dmp1 null mice is due to reduced osteoclast number, which is secondary to a reduced ratio of RANKL/OPG expressed by osteoclast supporting cells and (2) that osteoblast extracellular matrix mineralization, growth plate maturation, secondary ossification center formation, and osteoblast differentiation are phosphate-dependent. Finally, a working hypothesis is proposed to explain how phosphate and DMP1 control osteocyte maturation. © 2011 American Society for Bone and Mineral Research. PMID:21542006

Zhang, Rong; Lu, Yongbo; Ye, Ling; Yuan, Baozhi; Yu, Shibin; Qin, Chunlin; Xie, Yixia; Gao, Tian; Drezner, Marc K; Bonewald, Lynda F; Feng, Jian Q

2011-01-01

198

Factors and Mechanisms Involved in the Coupling from Bone Resorption to Formation: How Osteoclasts Talk to Osteoblasts  

PubMed Central

Bone remodeling is the fundamental means by which the quality as well as quantity of the skeleton is maintained throughout adult life. When bone remodeling goes awry, a metabolic bone disease such as osteoporosis ensues. Among multiple phases of the complex remodeling process, we focus in this review on factors and mechanisms that are involved in the coupling of bone formation to preceding resorption. PMID:25247154

Takeshita, Sunao

2014-01-01

199

The induction of bone formation by the recombinant human transforming growth factor-?3.  

PubMed

Implantation of recombinant human transforming growth factor-?3 (hTGF-?3) with coral-derived calcium carbonate-based macroporous bioreactors with limited conversion to hydroxyapatite (7% HA/CC) in the rectus abdominis muscle of the non-human primate Chacma baboon Papio ursinus induces endochondral bone formation. The exact mechanisms by which hTGF-?3 signalling induces bone in heterotopic sites of P. ursinus are not known. Coral-derived 7% HA/CC bioreactors with and without 125 ?g hTGF-?3 were implanted in triplicate in the rectus abdominis muscle of 6 adult baboons. 7% HA/CC bioreactors either with or without hTGF-?3 were loaded with 125 ?g of recombinant human Noggin (hNoggin), a bone morphogenetic proteins (BMPs) antagonist. Tissues on day 15, 60 and 90 were analysed by histomorphometry and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Down-regulation of BMP-2 characterized 7% HA/CC constructs preloaded with 125 ?g hNoggin with Noggin down-regulated on day 60 and 90 together with lack of TGF-?3 expression. Down-regulation of BMP-2 correlated with minimal bone formation by induction. hTGF-?3/hNoggin pre-treated bioreactors up-regulated BMP-2 but only on day 90 together with a significant down-regulation of Noggin on day 60 and 90, correlating with the induction of bone formation, albeit limited, on day 90 at the periphery of the macroporous bioreactors only. hTGF-?3 treated bioreactors significantly down-regulated BMP-2 on day 15 whilst up-regulating BMP-2 on day 60 and 90, together with down-regulation of Noggin on day 60 and 90 correlating with the prominent induction of bone formation. hTGF-?3 significantly up-regulated RUNX-2 and Osteocalcin expression on day 15 controlling the differentiation of progenitor stem cells into the osteoblastic lineage. The induction of bone as initiated by hTGF-?3 in the rectus abdominis muscle of P. ursinus is via the BMPs pathway with hTGF-?3 controlling the induction of bone formation by regulating the expression of BMPs via Noggin expression. These results unequivocally demonstrate that hTGF-?3 elicits bone induction by up-regulation of endogenous BMP-2 and is blocked by hNoggin. PMID:24438909

Klar, Roland M; Duarte, Raquel; Dix-Peek, Therese; Ripamonti, Ugo

2014-03-01

200

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

NASA Technical Reports Server (NTRS)

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.

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

1985-01-01

201

Feasibility of Using a Bone-Targeted, Macromolecular Delivery System Coupled with Prostaglandin E1 to Promote Bone Formation in Aged, Estrogen-Deficient Rats  

PubMed Central

Purpose Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer–Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods The uptake of FITC-labeled HPMA copolymer–Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions HPMA copolymers can be targeted to bone surfaces using Asp8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases. PMID:18758923

Miller, S. C.; Pan, H.; Wang, D.; Bowman, B. M.; Kopeckova, P.; Kopecek, J.

2009-01-01

202

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

PubMed Central

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

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

2012-01-01

203

The Wnt Serpentine Receptor Frizzled-9 Regulates New Bone Formation in Fracture Healing  

PubMed Central

Wnt signaling is a key regulator of bone metabolism and fracture healing. The canonical Wnt/?-catenin pathway is regarded as the dominant mechanism, and targeting this pathway has emerged as a promising strategy for the treatment of osteoporosis and poorly healing fractures. In contrast, little is known about the role of non-canonical Wnt signaling in bone. Recently, it was demonstrated that the serpentine receptor Fzd9, a Wnt receptor of the Frizzled family, is essential for osteoblast function and positively regulates bone remodeling via the non-canonical Wnt pathway without involving ?-catenin-dependent signaling. Here we investigated whether the Fzd9 receptor is essential for fracture healing using a femur osteotomy model in Fzd9?/? mice. After 10, 24 and 32 days the fracture calli were analyzed using biomechanical testing, histomorphometry, immunohistochemistry, and micro-computed tomography. Our results demonstrated significantly reduced amounts of newly formed bone at all investigated healing time points in the absence of Fzd9 and, accordingly, a decreased mechanical competence of the callus tissue in the late phase of fracture healing. In contrast, cartilage formation and numbers of osteoclasts degrading mineralized matrix were unaltered. ?-Catenin immunolocalization showed that canonical Wnt-signaling was not affected in the absence of Fzd9 in osteoblasts as well as in proliferating and mature chondrocytes within the fracture callus. The expression of established differentiation markers was not altered in the absence of Fzd9, whereas chemokines Ccl2 and Cxcl5 seemed to be reduced. Collectively, our results suggest that non-canonical signaling via the Fzd9 receptor positively regulates intramembranous and endochondral bone formation during fracture healing, whereas it does not participate in the formation of cartilage or in the osteoclastic degradation of mineralized matrix. The finding that Fzd9, in addition to its role in physiological bone remodeling, regulates bone repair may have implications for the development of treatments for poorly or non-healing fractures. PMID:24391920

Heilmann, Aline; Schinke, Thorsten; Bindl, Ronny; Wehner, Tim; Rapp, Anna; Haffner-Luntzer, Melanie; Nemitz, Claudia; Liedert, Astrid; Amling, Michael; Ignatius, Anita

2013-01-01

204

Early effect of platelet-rich plasma on bone healing in combination with an osteoconductive material in rat cranial defects  

Microsoft Academic Search

OBJECTIVE: The early effect of platelet-rich plasma (PRP) on bone regeneration in combination with dense biphasic hydroxyl apatite (HA)\\/beta-tricalcium phosphate (TCP) particles (ratio 60%\\/40%) was evaluated in rat cranial defects with a diameter of 6.2 mm. We hypothesize that PRP exerts its beneficial effect on bone regeneration within the first and second week after application in a bone defect combined

Adelina S. Plachokova; Juliette van den Dolder; Paul J. Stoelinga; John A. Jansen

2007-01-01

205

Proton gradient formation in early endosomes from proximal tubules.  

PubMed

Heavy endosomes were isolated from proximal tubules using a combination of magnesium precipitation and wheat-germ agglutinin negative selection techniques. Two small GTPases (Rab4 and Rab5) known to be specifically present in early endosomes were identified in our preparations. Endosomal acidification was followed fluorimetrically using acridine orange. In presence of chloride ions and ATP, the formation of a proton gradient (delta pH) was observed. This process is due to the activity of an electrogenic V-type ATPase present in the endosomal membrane since specific inhibitors bafilomycin and folimycin effectively prevented or eliminated endosomal acidification. In presence of chloride ions (K(m) = 30 mM) the formation of the proton gradient was optimal. Inhibitors of chloride channel activity such as DIDS and NPPB reduced acidification. The presence of sodium ions stimulated the dissipation of the proton gradient. This effect of sodium was abolished by amiloride derivative (MIA) but only when loaded into endosomes, indicating the presence of a physiologically oriented Na+/H(+)-exchanger in the endosomal membrane. Monensin restored the gradient dissipation. Thus three proteins (V-type ATPase, Cl(-)-channel, Na+/H(+)-exchanger) present in early endosomes isolated from proximal tubules may regulate the formation, maintenance and dissipation of the proton gradient. PMID:8914581

Marshansky, V; Vinay, P

1996-10-23

206

Diffuse idiopathic skeletal hyperostosis and new bone formation in male gouty subjects  

Microsoft Academic Search

Ninety-nine males with gout were identified and their radiographs examined for features of vertebral hyperostosis and entheseal changes (diffuse idiopathic skeletal hyperostosis, DISH). Of patients over the age of 45 years 43% fulfilled criteria for diagnosis of DISH. New bone formation in other regions of the skeleton was also common. The overhanging margin sign, seen in well developed tophi, was

G. O. Littlejohn; S. Hall

1982-01-01

207

Biocompatible, Biodegradable, and Enzymatic-Cleavable MRI Contrast Agents for Early Detection of Bone Metastatic Breast cancer.  

National Technical Information Service (NTIS)

This concept award proposes to design and test a novel peptide-based MRI contrast agent for early detection of bone metastasis from breast cancer. The proposed imaging agent is consist of bone targeting moiety of Asp8 and MRI imaging moiety of DOTA(Gd) wi...

X. Wang

2013-01-01

208

The application of histomorphometry and Fourier Transform Infrared Spectroscopy to the analysis of early Anglo-Saxon burned bone  

Microsoft Academic Search

Macroscopic examination, histomorphometry and Fourier Transform Infrared Spectroscopy (FTIR) are applied to the analysis of burned bones from the early Anglo-Saxon cemetery at Elsham in Lincolnshire, UK. These methods were undertaken to gain a greater understanding of pyre conditions from an archaeological context and the effects of burning on bone microstructure. Sixteen samples were employed for thin-section analysis while eight

Kirsty E. Squires; Tim J. U. Thompson; Meez Islam; Andrew Chamberlain

2011-01-01

209

Transgenic overexpression of ephrin b1 in bone cells promotes bone formation and an anabolic response to mechanical loading in mice.  

PubMed

To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tg (efnb1) ). Col3.6-Tg (efnb1) mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow stromal cells, calvarial osteoblasts, and osteoclasts, respectively. The long bones of both genders of Col3.6-Tg (efnb1) mice have increased trabecular bone volume, trabecular number, and trabecular thickness and decreased trabecular separation. Enhanced bone formation and decreased bone resorption contributed to this increase in trabecular bone mass in Col3.6-Tg (efnb1) mice. Consistent with these findings, our in vitro studies showed that overexpression of ephrin B1 increased osteoblast differentiation and mineralization, osterix and collagen 1A1 expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble clustered EphB2-Fc decreased osteoclast precursor differentiation into multinucleated cells. Furthermore, we demonstrated that the mechanical loading-induced increase in EphB2 expression and newly formed bone were significantly greater in the Col3.6-Tg (efnb1) mice than in WT littermate controls. Our findings that overexpression of ephrin B1 in bone cells enhances bone mass and promotes a skeletal anabolic response to mechanical loading suggest that manipulation of ephrin B1 actions in bone may provide a means to sensitize the skeleton to mechanical strain to stimulate new bone formation. PMID:23874863

Cheng, Shaohong; Kesavan, Chandrasekhar; Mohan, Subburaman; Qin, Xuezhong; Alarcon, Catrina M; Wergedal, Jon; Xing, Weirong

2013-01-01

210

Alisitos Formation, calcareous facies: Early Cretaceous episode of tectonic calm  

SciTech Connect

The Alisitos Formation (Aptian-Albian), shaped as a marine volcanic arc, crops out along the western side of the peninsula of Baja California bounding the Peninsular Range batholith. Lithologically, this formation is formed by volcanic-breccias, porphyritic flows, biohermal limestones, and tuffaceous and pyroclastic sediments. The distribution of the different facies depends on the nature of volcanism and the distance from a volcanic center, although the presence of massive biohermal limestone indicates that in the Early Cretaceous (during the tectonic episodes), the volcanic activity decreased to the level that the environmental conditions were favorable for the development of an organic reef barrier, behind an island arc. Such conditions existed south of the Agua Blanca fault and extended to El Arco, Baja California. Based upon field observations and petrological analysis of the Alisitos limestone, an attempt is made to recreate the environmental condition in the Punta China and San Fernando, Baja California, sites.

Suarez-Vidal, F.

1986-07-01

211

Alisitos Formation calcareous facies - Early Cretaceous episode of tectonic calm  

SciTech Connect

The Alisitos Formation (Aptian-Albian), shaped as a marine volcanic arc, crops out along the western side of Baja California bounding the Peninsula Range batholith. Lithologically, this formation is formed by volcanic breccias, porphyritic flows, biohermal limestones, and tuffaceous and pyroclastic sediments. The distribution of the different facies depends on the nature of volcanism and the distance from a volcanic center, although the presence of massive biohermal limestone indicates that in the Early Cretaceous (during tectonic episodes), the volcanic activity decreased to the level that the environmental conditions were favorable for the development of an organic barrier reef behind an island arc. Such conditions pertained south of the Agua Blanca fault and extended to El Arco, Baja California. Based on field observation and petrologic analysis in the Alisitos limestone, an attempt has been made to re-create the environmental condition in the Punta China and San Fernando, Baja California, sites.

Suarez-Vidal, F.

1986-04-01

212

p27(kip1) deficiency accelerates dentin and alveolar bone formation.  

PubMed

To assess the role of p27(kip1) in regulating dental formation and alveolar bone development, we compared the teeth and mandible phenotypes of homozygous p27(kip1) -deficient (p27(-/-) ) mice with their wild-type littermates at 2 weeks of age. At 2 weeks of age, dental mineral density, dental volume and dentin sialoprotein-immunopositive areas were increased significantly, whereas the predentin area : total dentin area and biglycan-immunopositive area : dentin area ratios were decreased significantly in p27(-/-) mice compared with their wild-type (WT) littermates. Mandible mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive areas, osteoblast number and activity and mRNA expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin and bone morphogenetic protein (bmp2) were all significantly increased in the mandibles, as was the number and surface of tartrate-resistant acid phosphatase-positive osteoclasts in the alveolar bone of p27(-/-) mice compared with their WT littermates. Furthermore, the percentage of proliferating cell nuclear antigen-positive cells in Hertwig's epithelial root sheath and protein expression of cyclin E and cyclin-dependent kinase 2 were increased significantly in p27(-/-) mice relative to their WT littermates. The results from this study indicate that p27 plays a negative regulatory role in dentin formation and alveolar bone development. PMID:24916068

Yin, Ying; Wang, Qun; Sun, Wen; Wang, Yuli; Chen, Ning; Miao, Dengshun

2014-10-01

213

Osteopotentia regulates osteoblast maturation, bone formation, and skeletal integrity in mice  

PubMed Central

During skeletal development and regeneration, bone-forming osteoblasts respond to high metabolic demand by active expansion of their rough endoplasmic reticulum (rER) and increased synthesis of type I collagen, the predominant bone matrix protein. However, the molecular mechanisms that orchestrate this response are not well understood. We show that insertional mutagenesis of the previously uncharacterized osteopotentia (Opt) gene disrupts osteoblast function and causes catastrophic defects in postnatal skeletal development. Opt encodes a widely expressed rER-localized integral membrane protein containing a conserved SUN (Sad1/Unc-84 homology) domain. Mice lacking Opt develop acute onset skeletal defects that include impaired bone formation and spontaneous fractures. These defects result in part from a cell-autonomous failure of osteoblast maturation and a posttranscriptional decline in type I collagen synthesis, which is concordant with minimal rER expansion. By identifying Opt as a crucial regulator of bone formation in the mouse, our results uncover a novel rER-mediated control point in osteoblast function and implicate human Opt as a candidate gene for brittle bone disorders. PMID:20440000

Jiang, Yebin; Zhao, Jenny J.; Mohr, Andreas; Roemer, Frank

2010-01-01

214

Improving osteoblast functions and bone formation upon BMP-2 immobilization on titanium modified with heparin.  

PubMed

The aim of this study was to develop bone morphogenetic protein-2 (BMP-2) immobilization on titanium (Ti) modified by heparin for improving osteoblast function in vitro and bone formation in vivo. The Ti surface was first modified with heparin and then immobilized with BMP-2 (BMP-2/Hep-Ti). The Ti and modified Ti were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle. In vitro studies demonstrated that osteoblasts cultured on BMP-2/Hep-Ti substrate increased ALP activity, calcium deposition, osteocalcin (OCN) and osteopontin (OPN) levels as compared to those cultured on Ti or BMP-2/Ti. In addition, intra-thread bone density and bone to implant contact ratio of BMP-2/Hep-Ti were significantly greater than those of Ti in the in vivo study. In conclusion, BMP-2 immobilized Ti modified heparin implants seemed to be a suitable delivery system for BMP-2 to improve osteoblast functions and new bone formation at the defect area around an implant. PMID:25263872

Kim, Sung Eun; Kim, Chang-Seop; Yun, Young-Pil; Yang, Dae Hyeok; Park, Kyeongsoon; Kim, Se Eun; Jeong, Chang-Mo; Huh, Jung-Bo

2014-12-19

215

The Effect of Heparan Sulfate Application on Bone Formation during Distraction Osteogenesis  

PubMed Central

Bone morphogenetic proteins (BMPs) are recognized for their ability to induce bone formation in vivo and in vitro. Their osteogenic and osteoinductive properties are tightly regulated by the secretion of specific BMP antagonists, which have been shown to physically bind and sometimes be blocked by the extracellular proteoglycan heparan sulphate side chains (from hereon referred to as HS). The purpose of this study was to investigate if local application of 5 µg of HS proteoglycan to a bone regenerate site in a mouse model of distraction osteogenesis (DO) can accelerate bone healing and affect the expression of key members of the BMP signaling pathway. DO was performed on the right tibia of 115 adult male wild-type mice. At mid-distraction (day 11), half the group was injected locally with 5 µg of HS, while the other half was injected with saline. The mice were sacrificed at 2 time-points: mid-consolidation (34 days) and full consolidation (51 days). The distracted tibial zone was then collected for analysis by ?CT, radiology, biomechanical testing, immunohistochemistry, and histology. While ?CT data showed no statistically significant difference in bone formation, the results of biomechanical testing in stiffness and ultimate force were significantly lower in the HS-injected bones at 51 days, compared to controls. Immunohistochemistry results also suggested a decrease in expression of several key members of the BMP signaling pathway at 34 days. Furthermore, wound dehiscence and infection rates were significantly elevated in the HS group compared to the controls, which resulted in a higher rate of euthanasia in the treatment group. Our findings demonstrate that exogenous application of 5 µg of HS in the distracted gap of a murine model had a negative impact on bone and wound healing. PMID:23457615

Gdalevitch, Marie; Kasaai, Bahar; Alam, Norine; Dohin, Bruno; Lauzier, Dominique; Hamdy, Reggie C.

2013-01-01

216

Pyk2 Regulates Megakaryocyte-Induced Increases in Osteoblast Number and Bone Formation  

PubMed Central

Pre-clinical and clinical evidence from megakaryocyte (MK) related diseases suggest that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We therefore examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 levels in OBs were significantly enhanced primarily due to increased Pyk2 gene transcription. Additionally, p53 and Mdm2 were both decreased in OBs upon MK stimulation, which would be permissive of cell cycle entry. We then demonstrated that OB number was markedly reduced when Pyk2?/? OBs, as opposed to wild-type (WT) OBs, were co-cultured with MKs. We also determined that MKs inhibit OB differentiation in the presence and absence of Pyk2 expression. Finally, given that MK replete spleen cells from GATA-1 deficient mice can robustly stimulate OB proliferation and bone formation in WT mice, we adoptively transferred spleen cells from these mice into Pyk2?/? recipient mice. Importantly, GATA-1 deficient spleen cells failed to stimulate an increase in bone formation in Pyk2?/? mice, suggesting in vivo the important role of Pyk2 in the MK-induced increase in bone volume. Further understanding of the signaling pathways involved in the MK-mediated enhancement of OB number and bone formation will facilitate the development of novel anabolic therapies to treat bone loss diseases. PMID:23362087

Cheng, Ying-Hua; Hooker, R. Adam; Nguyen, Khanh; Gerard-O’Riley, Rita; Waning, David L.; Chitteti, Brahmananda R.; Meijome, Tomas E.; Chua, Hui Lin; Plett, Artur P.; Orschell, Christie M.; Srour, Edward F.; Mayo, Lindsey D.; Pavalko, Fredrick M.; Bruzzaniti, Angela; Kacena, Melissa A.

2013-01-01

217

Mechanical regulation of localized and appositional bone formation around bone-interfacing implants  

E-print Network

dif- ferentiation; finite element analysis; porous-surfaced im- plant; plasma-sprayed implant. However, ef- forts to quantify the relationship between mechanical stimuli and tissue formation have in the healing tissue is difficult, and consequently mechanical stimuli are described by the applied loading

Simmons, Craig A.

218

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation  

PubMed Central

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

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

2012-01-01

219

Heterotopic Bone Formation Around Vessels: Pilot Study of a New Animal Model  

PubMed Central

Abstract To achieve an easily established, safe, and reproducible animal model for the study of heterotopic bone formation around vessels, a small animal series using New Zealand White rabbits was performed. Three different dosages of recombinant human bone morphogenic protein (rhBMP-2) carried by fibrin matrix were tested. A guided tissue regeneration (GTR) membrane sheet was formed into a tube and allowed to harden; it served both to maintain the space around the vessel bundle and to separate the fibrin matrix with rhBMP-2 from skeletal muscle. Wrapped around the femoral vessel bundle and fixed in place, the tube was filled with the fibrin matrix containing rhBMP-2. The surgical site was closed in layers, and the postoperative healing was uneventful. All animals resumed their full preoperative daily activities 3–4 days after the operation. No adverse events such as wound dehiscence or infection occurred, and all animals could be sacrified at the scheduled date. Micro–computed tomography and histological investigations showed heterotopic bone formation around the vessel bundle in the medium- and high-dosage rhBMP-2 groups. An easy, safe, and reproducible animal model that allows the study of heterotopic bone formation around vessels was successfully established. PMID:23914333

Cai, Wei-Xin; Zheng, Li-Wu; Weber, Franz E.; Li, Chun-Lei; Ma, Li; Ehrbar, Martin

2013-01-01

220

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

PubMed

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 signalling 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 nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, 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

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

221

Intrauterine growth restriction may not suppress bone formation at term, as indicated by circulating concentrations of undercarboxylated osteocalcin and Dickkopf-1.  

PubMed

The objective was to investigate circulating concentrations of bone formation markers (undercarboxylated osteocalcin [Glu-OC], an established marker of bone formation during fetal and early postnatal life], and Dickkopf-1 [DKK-1], a natural inhibitor of osteoblastogenesis during fetal development]) in intrauterine-growth-restricted (IUGR; associated with impaired fetal skeletal development) and appropriate-for-gestational-age (AGA) pregnancies. Circulating concentrations of Glu-OC and DKK-1 were determined by enzyme immunoassay in 40 mothers and their 20 asymmetric IUGR and 20 AGA singleton full-term fetuses and neonates on postnatal day 1 (N1) and 4 (N4). Parametric tests were applied in the statistical analysis. No significant differences in Glu-OC concentrations were observed between IUGR and AGA groups, whereas fetal DKK-1 concentrations were lower in the IUGR group (P = .028). In both groups, maternal Glu-OC and DKK-1 concentrations were lower than fetal, N1, and N4 concentrations (P ? .012 in all cases), whereas fetal Glu-OC concentrations were higher than N1 and N4 ones (P ? .037 in all cases). In addition, N1 Glu-OC concentrations were higher than N4 concentrations (P = .047). Finally, maternal Glu-OC and DKK-1 concentrations positively correlated with fetal, N1, and N4 ones (r ? 0.404, P ? .01 in all cases). Fetal/neonatal bone formation may not be impaired in full-term asymmetric IUGR infants, as indicated by the similar Glu-OC concentrations in both groups. Fetal DDK-1 concentrations are lower in the IUGR group, representing probably a compensatory mechanism, favoring the formation of mineralized bone. Fetal/neonatal bone turnover is markedly enhanced compared with maternal one and seems to be associated with the latter in both late pregnancy and early postpartum. PMID:21944272

Briana, Despina D; Gourgiotis, Dimitrios; Georgiadis, Anestis; Boutsikou, Maria; Baka, Stavroula; Marmarinos, Antonios; Hassiakos, Dimitrios; Malamitsi-Puchner, Ariadne

2012-03-01

222

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

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.

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

1987-12-01

223

Comparison of bone densitometry of the phalanges, distal forearm and axial skeleton in early postmenopausal women participating in the EPIC study  

Microsoft Academic Search

We present baseline bone densitometry from the Early Postmenopausal Interventional Cohort study (EPIC, sponsored by Merck, Sharp & Dohme) for the first time, in which 1609 women from England, Oregon, Hawaii and Denmark are participating to investigate the efficacy of daily oral alendronate to prevent early postmenopausal bone loss. We compared radiographic absorptiometry (RA) of the phalanges for bone mineral

P. Ravn; K. Overgaard; C. Huang; P. D. Ross; D. Green; M. Mcclung

1996-01-01

224

Dark Matter Heating and Early Core Formation in Dwarf Galaxies  

E-print Network

We present more results from a fully cosmological LCDM simulation of a group of isolated dwarf galaxies that has been shown to reproduce the observed stellar mass and cold gas content, resolved star formation histories, and metallicities of dwarfs in the Local Volume. Here we investigate the energetics and timetable of the cusp-core transformation. As suggested by previous work, supernova-driven gas outflows remove dark matter (DM) cusps and create kpc-size cores in all systems having a stellar mass above 1e6 Msun. The "DM core mass removal efficiency" -- dark mass ejected per unit stellar mass -- ranges today from a few to a dozen, and increases with decreasing host mass. Because dwarfs form the bulk of their stars prior to redshift 1 and the amount of work required for DM heating and core formation scales approximately as Mvir^{5/3}, the unbinding of the DM cusp starts early and the formation of cored profiles is not as energetically onerous as previously claimed. DM particles in the cusp typically migrate ...

Madau, Piero; Governato, Fabio

2014-01-01

225

NAA10 controls osteoblast differentiation and bone formation as a feedback regulator of Runx2.  

PubMed

Runt-related transcription factor 2 (Runx2) transactivates many genes required for osteoblast differentiation. The role of N-?-acetyltransferase 10 (NAA10, arrest-defective-1), originally identified in yeast, remains poorly understood in mammals. Here we report a new NAA10 function in Runx2-mediated osteogenesis. Runx2 stabilizes NAA10 in osteoblasts during BMP-2-induced differentiation, and NAA10 in turn controls this differentiation by inhibiting Runx2. NAA10 delays bone healing in a rat calvarial defect model and bone development in neonatal mice. Mechanistically, NAA10 acetylates Runx2 at Lys225, and this acetylation inhibits Runx2-driven transcription by interfering with CBF? binding to Runx2. Our study suggests that NAA10 acts as a guard ensuring balanced osteogenesis by fine-tuning Runx2 signalling in a feedback manner. NAA10 inhibition could be considered a potential strategy for facilitating bone formation. PMID:25376646

Yoon, Haejin; Kim, Hye-Lim; Chun, Yang-Sook; Shin, Dong Hoon; Lee, Kyoung-Hwa; Shin, Chan Soo; Lee, Dong Yeon; Kim, Hong-Hee; Lee, Zang Hee; Ryoo, Hyun-Mo; Lee, Mi-Ni; Oh, Goo Taeg; Park, Jong-Wan

2014-01-01

226

TWIST1 expression in breast cancer cells facilitates bone metastasis formation.  

PubMed

The transcription factor TWIST1 induces epithelial-mesenchymal transition and/or escape to the oncogenic-induced failsafe program, facilitating the intravasation of breast cancer cells in the systemic circulation and their dissemination to the lungs. Its involvement in breast cancer bone metastasis is unknown. To address this question, human osteotropic MDA-MB-231/B02 breast cancer cells were stably transfected with a Tet-inducible vector encoding for TWIST1, whose expression was specifically repressed in the presence of doxycycline (dox). The intra-arterial inoculation of transfectants expressing TWIST1 in immunodeficient mice substantially increased the extent of osteolytic lesions in these animals, being 50% larger than that of animals bearing mock-transfected tumors, as determined by radiography. This difference was accompanied by a sharp reduction of the bone volume (indicating a higher bone destruction) and a twofold increase in the tumor volume compared with mice bearing mock-transfected tumors, as determined by histomorphometry. Importantly, the suppression of TWIST1 expression in MDA-MB-231/B02 cells in the presence of dox abolished the stimulatory effect of TWIST1 on bone metastasis formation in vivo. Additionally, examination of the bone marrow from untreated and dox-treated animals on day 7 after tumor cell inoculation, at which time there was no evidence of radiographic osteolytic lesions, revealed that the number of tumor cell colonies that were recovered from the bone marrow of untreated mice was dramatically increased compared with that of dox-fed animals. In vitro, TWIST1 expression promoted tumor cell invasion and enhanced microRNA 10b (miR-10b) expression, a proinvasive factor, but was dispensable for growth of tumor cells. In vivo, the repression of miR-10b substantially decreased the presence of TWIST1-expressing breast cancer cells in the bone marrow. Overall, these results establish that TWIST1 facilitates breast cancer bone metastasis formation through a mechanism dependent of miR-10b, which leads to increase tumor burden and bone destruction. PMID:24619707

Croset, Martine; Goehrig, Delphine; Frackowiak, Agnieszka; Bonnelye, Edith; Ansieau, Stéphane; Puisieux, Alain; Clézardin, Philippe

2014-08-01

227

Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis.  

PubMed

Bone metastasis of breast cancer induces severe osteolysis with increased bone resorption. Osteoclast differentiation regulated by the receptor activator of NF-kappaB ligand (RANKL) in osteoblasts and matrix degradation induced by matrix metalloproteinases (MMPs) are thought to be involved in the process of bone resorption. When nude mice were inoculated with human breast cancer cells, MDA-MB-231(MDA-231), numerous osteoclasts resorbed bone and the degradation of the bone matrix markedly progressed in the femur and tibia with metastasis of the MDA-231 tumour. The expression of RANKL, MMP-13 and membrane-type 1-MMP mRNA was markedly elevated in bone with metastasis. When MDA-231 cells were cocultured with mouse calvaria, MDA-231 markedly induced bone resorption measured by calcium release from the calvaria, and the expression of RANKL, MMP-2 and MMP-13 was elevated in the calvaria after the coculture. The separation of MDA-231 from the calvaria using filter insert showed decreased bone resorption, suggesting that cell-to-cell interaction is essential for cancer-induced bone resorption. Adding MDA-231 cells to bone marrow cultures markedly induced osteoclast formation, and the expression of RANKL in osteoblasts was enhanced by contact with the cell surface of MDA-231 cells. These results indicate that RANKL-induced osteoclast formation and MMP-dependent matrix degradation are associated with osteolysis because of bone metastasis of breast cancer. PMID:12698202

Ohshiba, T; Miyaura, C; Inada, M; Ito, A

2003-04-22

228

Erythropoietin Mediated Bone Formation Is Regulated by mTOR Signaling  

PubMed Central

The role of erythropoietin (Epo) and Epo/Epo receptor (EpoR) signaling pathways for production of red blood cells are well established. However, little is known about Epo/EpoR signaling in non-hematopoietic cells. Recently, we demonstrated that Epo activates JAK/STAT signaling in hematopoietic stem cells (HSCs), leading to the production of bone morphogenetic protein 2 (BMP2) and bone formation and that Epo also directly activate mesenchymal cells to form osteoblasts in vitro. In this study, we investigated the effects of mTOR signaling on Epo-mediated osteoblastogenesis and osteoclastogenesis. We found that mTOR inhibition by rapamycin blocks Epo-dependent and -independent osteoblastic phenotypes in human bone marrow stromal cells (hBMSCs) and ST2 cells, respectively. Furthermore, we found that rapamycin inhibits Epo-dependent and -independent osteoclastogenesis in mouse bone marrow mononuclear cells and Raw264.7 cells. Finally, we demonstrated that Epo increases NFATc1 expression and decreases cathepsin K expression in an mTOR-independent manner, resulting in an increase of osteoclast numbers and a decrease in resorption activity. Taken together, these results strongly indicate that mTOR signaling plays an important role in Epo-mediated bone homeostasis. PMID:21898543

Kim, Jinkoo; Jung, Younghun; Sun, Hongli; Joseph, Jeena; Mishra, Anjali; Shiozawa, Yusuke; Wang, Jingcheng; Krebsbach, Paul H.; Taichman, Russell S.

2011-01-01

229

Mesenchymal stroma cells trigger early attraction of M1 macrophages and endothelial cells into fibrin hydrogels, stimulating long bone healing without long-term engraftment.  

PubMed

Implantation of mesenchymal stroma cells (MSCs) is an attractive approach to stimulate closure of large bone defects but an optimal carrier has yet to be defined. MSCs may display trophic and/or immunomodulatory features or stimulate bone healing by their osteogenic activity. The aim of this study was to unravel whether fibrin hydrogel supports early actions of implanted MSCs, such as host cell recruitment, immunomodulation and tissue regeneration, in long bone defects. Female rats received cell-free fibrin or male MSCs embedded in a fibrin carrier into plate-stabilized femoral bone defects. Removed callus was analyzed for host cell invasion (day 6), local cytokine expression (days 3 and 6) and persistence of male MSCs (days 3, 6, 14 and 28). Fibrin-MSC composites triggered fast attraction of host cells into the hydrogel while cell-free fibrin implants were not invaded. A migration front dominated by M1 macrophages and endothelial progenitor cells formed while M2 macrophages remained sparse. Only MSC-seeded fibrin hydrogel stimulated early tissue maturation and primitive vessel formation at day 6 in line with significantly higher VEGF mRNA levels recorded at day 3. Local TNF-?, IL-1? and IL-10 expression indicated a balanced immune cell activity independent of MSC implantation. Implanted MSCs persisted until day 14 but not day 28. Our results demonstrate that fibrin hydrogel is an attractive carrier for MSC implantation into long bone defects, supporting host cell attraction and pro-angiogenic activity. By this angiogenesis, implant integration and tissue maturation was stimulated in long bone healing independent of long-term engraftment of implanted MSCs. PMID:25058402

Seebach, Elisabeth; Freischmidt, Holger; Holschbach, Jeannine; Fellenberg, Jörg; Richter, Wiltrud

2014-11-01

230

Formation of early water oceans on rocky planets  

NASA Astrophysics Data System (ADS)

Terrestrial planets, with silicate mantles and metallic cores, are likely to obtain water and carbon compounds during accretion. Here I examine the conditions that allow early formation of a surface water ocean (simultaneous with cooling to clement surface conditions), and the timeline of degassing the planetary interior into the atmosphere. The greatest fraction of a planet's initial volatile budget is degassed into the atmosphere during the end of magma ocean solidification, leaving only a small fraction of the original volatiles to be released into the atmosphere through later volcanism. Rocky planets that accrete with water in their bulk mantle have two mechanisms for producing an early water ocean: First, if they accrete with at least 1 to 3 mass% of water in their bulk composition, liquid water may be extruded onto the planetary surface at the end of magma ocean solidification. Second, at initial water contents as low as 0.01 mass% or lower, during solidification a massive supercritical fluid and steam atmosphere is produced that collapses into a water ocean upon cooling. The low water contents required for this process indicate that rocky super-Earth exoplanets may be expected to commonly produce water oceans within tens to hundreds of millions of years of their last major accretionary impact, through collapse of their atmosphere.

Elkins-Tanton, Linda T.

2011-04-01

231

New bone formation enhanced by ADSCs overexpressing hRunx2 during mandibular distraction osteogenesis in osteoporotic rabbits.  

PubMed

Promoting new bone formation during distraction osteogenesis (DO) in elderly patients with osteoporosis is still a challenge. In this study, we investigated the effect of gene therapy using local Runt-related gene 2 on new bone formation during osteoporotic mandibular DO in rabbits. First, we successfully established a mandibular osteoporotic animal model by ovariectomizing rabbits. Second, the right mandibles of the osteoporotic rabbits were distracted after corticotomy. The distraction gap of the rabbits in Group A2 and B2 were injected with Adv-hRunx2-GFP-transfected adipose-derived stromal cells (ADSCs) and Adv-GFP-transfected ADSCs, respectively. Rabbits in Groups C2 (ovariectomized control) and D2 (sham surgery control) were injected with physiologic saline. New-generation bone tissue in the distraction gap was analyzed via plain radiographic examinations, micro-computed tomography, histological examinations, and biomechanical testing at weeks 3, 6, and 9 of the consolidation period. Results of above examinations showed that no ideal new bone formation was observed in Groups B2 and C2, but obvious ideal new bone formation was observed in Group A2 and D2. The results suggested that gene therapy using rhRunx2-modified ADSCs promoted new bone formation during osteoporotic mandibular DO and effectively compensated for the detrimental effects of systemic osteoporosis on new bone formation. PMID:24522890

Sun, Jing-Jing; Zheng, Xiao-Hui; Wang, Li-Ya; Liu, Lei; Jing, Wei; Lin, Yun-Feng; Tian, Weidong; Tang, Wei; Long, Jie

2014-05-01

232

Bone marrow microenvironment in myelomagenesis: its potential role in early diagnosis  

PubMed Central

Multiple myeloma (MM) is the second most common hematological malignancy, with an overall survival of 4–6 years. It is always preceded by a premalignant stage called monoclonal gammopathy of unknown significance (MGUS). Importantly, at this time we lack reliable predictors to determine who will progress from MGUS to MM, and who will remain stable. The bone marrow microenvironment plays a key role in myelomagenesis (growth, survival and migration of malignant plasma cells). In the present review, we summarize and discuss our current understanding of the bone marrow microenvironment and its compartments in relation to myelomagenesis. Although it remains to be proven, we believe that an improved characterization of the cellular constituents, the extracellular matrix components and the soluble factors of the bone marrow could open up novel avenues to better understand underlying mechanisms of the transformation from MGUS to MM. Ultimately, this will lead to the development of early treatment of high-risk precursor disease aimed to delay/prevent MM. PMID:20465501

Balakumaran, Arun; Robey, Pamela Gehron; Fedarko, Neal; Landgren, Ola

2010-01-01

233

Gene expression profiling and histomorphometric analyses of the early bone healing response around nanotextured implants  

PubMed Central

While in vitro studies have shown that nanoscale surface modifications influence cell fate and activity, there is little information on how they modulate healing at the bone–implant interface. Aim This study aims to investigate the effect of nanotopography at early time intervals when critical events for implant integration occur. Materials & methods Untreated and sulfuric acid/hydrogen peroxide-treated machined-surface titanium alloy implants were placed in rat tibiae. Samples were processed for DNA microarray analysis and histomorphometry. Results At both 3 and 5 days, the gene expression profile of the healing tissue around nanotextured implants differed from that around machined-surface implants or control empty holes, and were accompanied by an increase in bone–implant contact on day 5. While some standard pathways such as the immune response predominated, a number of unclassified genes were also implicated. Conclusion Nanotexture elicits an initial gene response that is more complex than suspected so far and favors healing at the bone–implant interface. PMID:23286527

Wazen, Rima M; Kuroda, Shingo; Nishio, Clarice; Sellin, Karine; Brunski, John B; Nanci, Antonio

2013-01-01

234

Star Formation Bimodality in Early-type Galaxies  

NASA Astrophysics Data System (ADS)

We compute the properties of a sample of 221 local, early-type galaxies with a spectral energy distribution (SED) modeling software, CIGALEMC. Concentrating on the star-forming (SF) activity and dust contents, we derive parameters such as the specific star formation rate (sSFR), the dust luminosity, dust mass, and temperature. In our sample, 52% is composed of elliptical (E) galaxies and 48% of lenticular (S0) galaxies. We find a larger proportion of S0 galaxies among galaxies with a large sSFR and large specific dust emission. The stronger activity of S0 galaxies is confirmed by larger dust masses. We investigate the relative proportion of active galactic nuclei (AGNs) and SF galaxies in our sample using spectroscopic Sloan Digital Sky Survey data and near-infrared selection techniques, and find a larger proportion of AGN-dominated galaxies in the S0 sample than the E one. This could corroborate a scenario where blue galaxies evolve into red ellipticals by passing through an S0 AGN active period while quenching its star formation. Finally, we find a good agreement comparing our estimates with color indicators.

Amblard, A.; Riguccini, L.; Temi, P.; Im, S.; Fanelli, M.; Serra, P.

2014-03-01

235

Enhancement of ectopic bone formation by bone morphogenetic protein-2 released from a heparin-conjugated poly( l-lactic- co-glycolic acid) scaffold  

Microsoft Academic Search

In this study, a heparin-conjugated poly(l-lactic-co-glycolic acid) (HP-PLGA) scaffold was developed for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then used to address the hypothesis that BMP-2 delivered from this scaffold could enhance ectopic bone formation. We found the amount of heparin conjugated to the PLGA scaffolds could be increased up to 3.2-fold by using scaffolds made from

Oju Jeon; Su Jin Song; Sun-Woong Kang; Andrew J. Putnam; Byung-Soo Kim

2007-01-01

236

Dark Matter Heating and Early Core Formation in Dwarf Galaxies  

NASA Astrophysics Data System (ADS)

We present more results from a fully cosmological ?CDM simulation of a group of isolated dwarf galaxies that has been shown to reproduce the observed stellar mass and cold gas content, resolved star formation histories, and metallicities of dwarfs in the Local Volume. Here we investigate the energetics and timetable of the cusp-core transformation. As suggested by previous work, supernova-driven gas outflows remove dark matter (DM) cusps and create kiloparsec-size cores in all systems having a stellar mass M * > 106 M ?. The "DM core mass removal efficiency"—dark mass ejected per unit stellar mass—ranges today from a few to a dozen, and increases with decreasing host mass. Because dwarfs form the bulk of their stars prior to redshift 1 and the amount of work required for DM heating and core formation scales approximately as M_vir^{5/3}, the unbinding of the DM cusp starts early and the formation of cored profiles is not as energetically onerous as previously claimed. DM particles in the cusp typically migrate to 2-3 core radii after absorbing a few percent of the energy released by supernovae. The present-day slopes of the inner DM mass profiles, ? ? dlog M/dlog R ~= 2.5-3, of the simulated "Bashful" and "Doc" dwarfs are similar to those measured in the luminous Fornax and Sculptor dwarf spheroidals. None of the simulated galaxies has a circular velocity profile exceeding 20 km s-1 in the inner 1 kpc, implying that supernova feedback is key to solve the "too-big-to-fail" problem for Milky Way subhalos.

Madau, Piero; Shen, Sijing; Governato, Fabio

2014-07-01

237

Evaluation of a Thiolated Chitosan Scaffold for Local Delivery of BMP-2 for Osteogenic Differentiation and Ectopic Bone Formation  

PubMed Central

Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for drug delivery. However, its use as a scaffold for bone formation has not been investigated. The aim of this study was to evaluate the potential of Thio-CS in bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study showed that BMP-2 interacted with the Thio-CS and did not affect the swelling behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased osteoblastic cell differentiation but did not show any cytotoxicity until 21 days. Analysis of the in vivo ectopic bone formation at 4 weeks of posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel carrier. Taken together, Thio-CS system might be useful for delivering osteogenic protein BMP-2 and present a promising bone regeneration strategy. PMID:24024213

Bae, In-Ho; Jeong, Byung-Chul; Kim, Sun-Hun; Koh, Jeong-Tae

2013-01-01

238

Haversian bone formation rates determined by a new method in a mastodon, and in human diabetes mellitus and osteoporosis  

Microsoft Academic Search

Counts of the population densities of secondary osteons allow the determination of the haversian bone formation rate without the use of a tissue marker and can do so in paleontological as well as contemporary bone specimens. Using this technique, together with tetracycline markers, such rates were measured in 180 normal humans, in 10 diabetics, in 5 patients with osteogenesis imperfecta,

K. Wu; K. E. Schubeck; H. M. Frost; A. Villanueva

1970-01-01

239

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

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

240

Heparanase Expression and Activity Influences Chondrogenic and Osteogenic Processes During Endochondral Bone Formation  

PubMed Central

Endochondral bone formation is a highly orchestrated process involving coordination among cell-cell, cell-matrix and growth factor signaling that eventually results in the production of mineralized bone from a cartilage template. Chondrogenic and osteogenic differentiation occur in sequence during this process, and the temporospatial patterning clearly requires the activities of heparin binding growth factors and their receptors. Heparanase (HPSE) plays a role in osteogenesis, but the mechanism by which it does so is incompletely understood. We used a combination of ex vivo and in vitro approaches and a well described HPSE inhibitor, PI-88 to study HPSE in endochondral bone formation. In situ hybridization and immunolocalization with HPSE antibodies revealed that HPSE is expressed in the peri-chondrium, peri-osteum, and at the chondro-osseous junction, all sites of key signaling events and tissue morphogenesis. Transcripts encoding Hpse also were observed in the pre-hypertrophic zone. Addition of PI-88 to metatarsals in organ culture reduced growth and suggested that HPSE activity aids the transition from chondrogenic to osteogenic processes in growth of long bones. To study this, we used high density cultures of ATDC5 pre-chondrogenic cells grown under conditions favoring chondrogenesis or osteogenesis. Under chondrogenic conditions, HPSE/Hpse was expressed at high levels during the mid-culture period, at the onset of terminal chondrogenesis. PI-88 addition reduced chondrogenesis and accelerated osteogenesis, including a dramatic up-regulation of osteocalcin levels. In normal growth medium, addition of PI-88 reduced migration of ATDC-5 cells, suggesting that HPSE facilitates cartilage replacement by bone at the chondro-osseous junction by removing the HS component of proteoglycans, such as perlecan/HSPG2, that otherwise prevent osteogenic cells from remodeling hypertrophic cartilage. PMID:18589009

Brown, A. J.; Alicknavitch, M.; D'Souza, S.S.; Daikoku, T.; Kirn-Safran, C.B.; Marchetti, D.; Carson, D. D.; Farach-Carson, M.C.

2008-01-01

241

Ectopic bone formation in severely combat-injured orthopedic patients -- a hematopoietic niche.  

PubMed

Combat-related heterotopic ossification (HO) has emerged as a common and problematic complication of modern wartime extremity injuries, contributing to substantial patient morbidity and loss of function. We have previously reported that HO-forming patients exhibit a more pronounced systemic and local inflammatory response very early in the wound healing process. Moreover, traumatized muscle-derived mesenchymal progenitor cells from these patients have a skewed differentiation potential toward bone. Here, we demonstrate that HO lesions excised from this patient population contain highly vascularized, mature, cancellous bone containing adipogenic marrow. Histologic analysis showed immature hematopoietic cells located within distinct foci in perivascular regions. The adipogenic marrow often contained low numbers of functional erythroid (BFU-E), myeloid (CFU-GM, CFU-M) and multilineage (CFU-GEMM) colony-forming hematopoietic progenitor cells (HPCs). Conversely, tissue from control muscle and non-HO traumatic wound granulation tissue showed no evidence of hematopoietic progenitor cell activity. In summary, our findings suggest that ectopic bone can provide an appropriate hematopoietic microenvironment for supporting the proliferation and differentiation of HPCs. This reactive and vibrant cell population may help maintain normal hematopoietic function, particularly in those with major extremity amputations who have sustained both massive blood loss, prompting systemic marrow stimulation, as well as loss of available native active marrow space. These findings begin to characterize the functional biology of ectopic bone and elucidate the interactions between HPC and non-hematopoietic cell types within the ectopic intramedullary hematopoietic microenvironmental niche identified. PMID:23727270

Davis, Thomas A; Lazdun, Yelena; Potter, Benjamin K; Forsberg, Jonathan A

2013-09-01

242

Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.  

PubMed

Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 ?g/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (p<0.0001). This was associated with a trend of higher Tb.N, Tb.Th, DA, an inferior Conn.D and a lower bone turnover as shown by the decreases of osteoid parameters, MS/BS, Ac.f in LV1 when compared to IC. In addition, the ratio PYD/DPD was 4 times higher in LV1 than IC. After 3 months, significant decreases of sALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly only in LV1 (p<0.05) with a trend of increases in MS/BS and BFR/BS, compared to LV1-CTRL. In conclusion, in adult ewes, the bone mass, microarchitecture, remodeling and collagen crosslink content differ according to the bone site (iliac crest and vertebra). Furthermore, after 3 months, the responses to ZOL and TPTD were of different magnitude and delay between the two bone sites. The distinction of bone sites to study the early effects of anti-osteoporotic therapies appears meaningful in order to approach their site-specific anti-fracture efficacy. PMID:22796591

Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

2012-10-01

243

Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation  

PubMed Central

Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

2014-01-01

244

Efficiently engineered cell sheet using a complex of polyethylenimine-alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation.  

PubMed

Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine-alginate (PEI-al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI-al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI-al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

2014-01-01

245

Multiple myeloma presenting as plasmacytoma of the jaws showing prominent bone formation during chemotherapy  

PubMed Central

A 65-year-old female visited our hospital complaining of a swelling on the left cheek area of 2 years' duration. A panoramic radiograph revealed an ill-defined osteolytic radiolucent bony lesion involving the left mandibular angle, ascending ramus, coronoid process and condylar process. Histological examination showed the mandibular lesion to be a plasmacytoma, and a systemic work-up was obtained to rule out multiple myeloma. Contrast-enhanced CT images showed a well-defined and slightly enhanced round mass on the left ramal area, accompanied by the destruction of the left ramus and posterior maxilla. An 18F-fluorodeoxy-glucose positron emission tomography CT (18F-FDG PET/CT) scan revealed a hypermetabolic mass extending from the left mandible to the left maxillary sinus. The patient had M-protein in serum and urine, plasma cells up to 36.5% on bone marrow biopsy and anaemia as a clinical complication. The patient was diagnosed with multiple myeloma and received chemotherapy with thalidomide, cyclophosphamide and dexamethasone. A PET/CT scan taken 6 months later revealed that the hypermetabolic mass had disappeared and there was remarkable bone formation on the left mandible compared with a previous PET/CT scan. A panoramic radiograph taken 8 months later also demonstrated a prominent bone formation of the affected site. To the best of our knowledge, the current case is the first report of multiple myeloma presenting as plasmacytoma of the mandible with an FDG PET/CT scan. The lesion was solitary at diagnosis, and remarkable bone formation was newly observed on the radiographic examination during chemotherapy. PMID:23520399

An, S-Y; An, C-H; Choi, K-S; Heo, M-S

2013-01-01

246

Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival.  

PubMed

Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has clinical potential to treat fractures or to slow osteoarthritic progression by enhancing chondrocyte survival and slowing hypertrophy.Cell Death and Disease (2014) 5, e1522; doi:10.1038/cddis.2014.480; published online 13 November 2014. PMID:25393478

Eaton, G J; Zhang, Q-S; Diallo, C; Matsuzawa, A; Ichijo, H; Steinbeck, M J; Freeman, T A

2014-01-01

247

In vivo formation of bone and haematopoietic territories by transplanted human bone marrow stromal cells generated in medium with and without osteogenic supplements.  

PubMed

Autologous transplantation of human bone marrow stromal cells (BMSCs) has been successfully used for bone reconstruction. However, in order to advance this approach into the mainstream of bone tissue engineering, the conditions for BMSC cultivation and transplantation must be optimized. In a recent report, cultivation with dexamethasone (Dex) significantly increased bone formation by human BMSCs in vivo. Based on this important conclusion, we analysed the data accumulated by our laboratory, where human BMSCs have been routinely generated using media both with and without a combination of two osteogenic supplements: Dex at 10(-8) ?m and ascorbic acid phosphate (AscP) at 10(-4) ?m. Our data demonstrate that for 22/24 donors, BMSC strains propagated with and without Dex/AscP formed similar amounts of bone in vivo. Thus, human BMSCs do not appear to need to be induced to osteogenic differentiation ex vivo prior to transplantation. Similarly, for 12/14 donors, BMSC strains cultured with and without Dex/AscP formed haematopoietic territories to a comparable extent. While Dex/AscP did not increase bone formation, they significantly stimulated BMSC in vitro proliferation without affecting the number of BMSC colonies formed by the colony-forming units-fibroblasts. We conclude that for the substantial majority of donors, Dex/AscP have no effect on the ability of BMSCs to form bone and myelosupportive stroma in vivo. However, due to increased BMSC proliferation, the total osteogenic population obtained from a single marrow sample is larger after cultivation with Dex/AscP than without them. Secondary to increased BMSC proliferation, Dex/AscP may stimulate bone formation if BMSCs and/or the transplantation system are less than optimal. Published 2011. This article is a U.S. Government work and is in the public domain in the USA. PMID:22052864

Kuznetsov, Sergei A; Mankani, Mahesh H; Robey, Pamela Gehron

2013-03-01

248

Low-Intensity Pulsed Ultrasound Accelerates Osteoblast Differentiation and Promotes Bone Formation in an Osteoporosis Rat Model  

Microsoft Academic Search

Objective: We examined the effects of low-intensity pulsed ultrasound (LIPUS) on cell differentiation, bone mineralized nodule formation and core-binding factor A1 (Cbfa1) expression in a normal human osteoblast (NHOst) cell line and bone formation in an osteoporosis animal model. Methods: NHOst cells were cultured in vitro in medium with or without LIPUS stimulation. The ultrasound stimulation frequency was 1.0 MHz

Shuliang Wu; Yumi Kawahara; Tomotaka Manabe; Kazuyuki Ogawa; Masaya Matsumoto; Akira Sasaki; Louis Yuge

2009-01-01

249

Interactions between Family Investments, Early-Life Shocks and Human Capital Formation among Children  

E-print Network

in children's exposure to a negative shock at different periods early in life. I Capital Formation among Children Guest Lecture by Maria Rosales Rueda Harris investigate the persistent effect of negative shocks early in life on children

Rose, Michael R.

250

Formation of a FGF-2 and calcium phosphate composite layer on a hydroxyapatite ceramic for promoting bone formation.  

PubMed

Fibroblast growth factor-2 (FGF-2) was immobilized on a hydroxyapatite (HAP) ceramic in supersaturated calcium phosphate solution prepared using solutions corresponding to clinically approved infusion fluids. To avoid the risk of FGF-2 denaturation, FGF-2 immobilization was carried out at 25 degrees C. FGF-2 was successfully immobilized on HAP ceramic surfaces by deposition with calcium phosphate to form a FGF-2 and calcium phosphate composite layer. A maximum of 2.72 +/- 0.01 microg cm(-2) of FGF-2 was immobilized in the composite layer formed on the HAP ceramic under the optimum condition. A FGF-2-immobilized HAP ceramic is likely to have the ability to release a sufficient amount of FGF-2 to promote bone formation. FGF-2 released from a FGF-2-immobilized HAP ceramic maintained its biological activity, since the proliferation of fibroblastic NIH3T3 was promoted. Therefore, the FGF-2-immobilized HAP ceramic is expected to be a useful material for promoting new bone formation. PMID:18458464

Sogo, Yu; Ito, Atsuo; Onoguchi, Masahiro; Oyane, Ayako; Tsurushima, Hideo; Ichinose, Noboru

2007-09-01

251

Alphavbeta5-integrins mediate early steps of metastasis formation.  

PubMed

Tumour cell adhesion within the microvasculature of host organs, its stabilisation and cell invasion into the host organs, appear to be important steps in the formation of distant metastases. Intravital fluorescence-video microscopy was used to investigate the early steps in metastasis formation of colon carcinoma cells within the liver, which is the main target organ of colorectal carcinomas. The involvement of alphav-integrins was analysed in vivo using HT-29 cells after treatment with different function-blocking antibodies [pan-alphav (n=9 animals), specific alphavbeta3 (n=8 animals) and alphavbeta5 (n=8 animals)] or linear Arg-Gly-Asp (RGD)-containing peptides (RGD-peptides) (n=6 animals). Treatment with anti-alphav and anti-alphavbeta5 antibodies resulted in significantly (P<0.001) decreased tumour cell adhesion in vivo within the hepatic microvasculature. Cells treated with anti-alphavbeta3 antibodies or unspecific immunoglobulin-G (IgG) did not show significant changes in their adhesive properties. Furthermore, inhibition of cell adhesion was achieved by linear RGD-peptides in a dose-dependent manner. Relative numbers of migrated cells were not affected by any of the treatments. These results suggest that alphav-integrins, especially alphavbeta5, can influence the ability of circulating tumour cells to adhere within the hepatic microvessels. In contrast, migration of adherent cells into the liver parenchyma was not affected by alphav-integrin inhibition. Our findings support the hypothesis that specific interactions between circulating tumour cells and host organs are required for organ-specific tumour cell arrest. PMID:15862757

Enns, Andreas; Korb, Timo; Schlüter, Kerstin; Gassmann, Peter; Spiegel, Hans-Ullrich; Senninger, Norbert; Mitjans, Francesc; Haier, Jörg

2005-05-01

252

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

PubMed Central

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.

Zhang, Jianying; Wang, James H-C

2014-01-01

253

Resorption of, and bone formation from, new beta-tricalcium phosphate-monocalcium phosphate cements: an in vivo study.  

PubMed

Hard cylinders (4.7 x 10 mm) of two kinds of beta-tricalcium phosphate-monocalcium phosphate monohydrate-calcium sulfate hemihydrate (beta-TCP-MCPM-CSH) cements with and without beta-TCP granules (500-1000 microns) were implanted into holes drilled in rabbit femoral condyles for up to 16 weeks. Empty cavities were used as control. Cement resorption and new bone formation in the cylinders were evaluated with contact microradiography and quantified through an automatic image analysis system. At 4 weeks, both kinds of cement cylinders were surrounded by new bone. At 8 weeks, except for beta-TCP granules, both cement cylinders were almost completely resorbed and replaced by bone tissue. At 16 weeks the bone in the cavities of both cements recovered a trabecular pattern, but only the bone trabeculae in the initial cavity of the cement with beta-TCP granules became thick and mature. However, the cavities of the empty control were still empty and large. These results show that the beta-TCP-MCPM-CSH cements stimulate bone formation and are rapidly replaced by bone tissue. When added with nonresorbable beta-TCP granules, this cement maintains bone formation for a longer time. PMID:9019484

Ohura, K; Bohner, M; Hardouin, P; Lemaître, J; Pasquier, G; Flautre, B

1996-02-01

254

Si-Wu-tang extract stimulates bone formation through PI3K/Akt/NF-?B signaling pathways in osteoblasts  

PubMed Central

Background Si-Wu-Tang (SWT), a Traditional Chinese Medicine (TCM) formula, is widely used for the treatment of gynopathies diseases such as menstrual discomfort, climacteric syndrome, dysmenorrhea, and other estrogen-related diseases. Recent studies have shown that SWT can treat primary dysmenorrhea, have anti-pruritic anti-inflammatory effects, and protect against radiation-induced bone marrow damage in an animal model. It has been reported that anti-inflammatory and anti-oxidant agents have the potential to treat osteoporosis by increasing bone formation and/or suppressing bone resorption. However, the effect of SWT on bone cell function has not yet been reported. Methods Alkaline phosphatase (ALP), bone morphogenetic proteins (BMP)-2, and osteopontin (OPN) mRNA expression was analyzed by qPCR. The mechanism of action of SWT extract was investigated using western blotting. The in vivo anti-osteoporotic effect of SWT extract was assessed in ovariectomized mice. Results Here, we report that SWT increases ALP, BMP-2, and OPN expression as well as bone mineralization. In addition, we show that the PI3K, Akt, and NF-?B signaling pathways may be involved in the SWT-mediated increase in gene expression and bone mineralization. Notably, treatment of mice with SWT extract prevented bone loss induced by ovariectomy in vivo. Conclusion SWT may be used to stimulate bone formation for the treatment of osteoporosis. PMID:24156308

2013-01-01

255

The Implications of the Early Formation of Life on Earth  

E-print Network

One of the most interesting unsolved questions in science today is the question of life on other planets. At the present time it is safe to say that we do not have much of an idea as to whether life is common or exceedingly rare in the universe, and this will probably not be solved for certain unless definitive evidence of extraterrestrial life is found in the future. Our presence on Earth is just as consistent with the hypothesis that life is extremely rare as it is with the hypothesis that it is common, since if there was only one planet with intelligent life, we would find ourselves on it. However, we have more information than this, such as the the surprisingly short length of time it took for life to arise on Earth. Previous authors have analysed this information, concluding that it is evidence that the probability of abiogenesis is moderate ($>$ 13% with 95% probability) and cannot be extremely small. In this paper I use simple probabilistic model to show that this conclusion was based more on an unintentional assumption than on the data. While the early formation of life on Earth provides some evidence in the direction of life being common, it is far from conclusive, and in particular does not rule out the possibility that abiogenesis has only occurred once in the history of the universe.

Brendon J. Brewer

2008-07-31

256

NF-?B RELA-deficient bone marrow macrophages fail to support bone formation and to maintain the hematopoietic niche after lethal irradiation and stem cell transplantation.  

PubMed

Bone remodeling and hematopoiesis are interrelated and bone marrow (BM) macrophages are considered to be important for both bone remodeling and maintenance of the hematopoietic niche. We found that NF-?B Rela-deficient chimeric mice, generated by transplanting Rela (-/-) fetal liver cells into lethally irradiated hosts, developed severe osteopenia, reduced lymphopoiesis and enhanced mobilization of hematopoietic stem and progenitor cells when BM cells were completely substituted by Rela-deficient cells. Rela (-/-) hematopoietic stem cells from fetal liver had normal hematopoietic ability, but those harvested from the BM of osteopenic Rela (-/-) chimeric mice had reduced repopulation ability, indicating impairment of the microenvironment for the hematopoietic niche. Osteopenia in Rela (-/-) chimeric mice was due to reduced bone formation, even though osteoblasts differentiated from host cells. This finding indicates impaired functional coupling between osteoblasts and hematopoietic stem cell-derived cells. Rela-deficient BM macrophages exhibited an aberrant inflammatory phenotype, and transplantation with wild-type F4/80(+) BM macrophages recovered bone formation and ameliorated lymphopoiesis in Rela (-/-) chimeric mice. Therefore, RELA in F4/80(+) macrophages is important both for bone homeostasis and for maintaining the hematopoietic niche after lethal irradiation and hematopoietic stem cell transplantation. PMID:24908679

Mise-Omata, Setsuko; Alles, Neil; Fukazawa, Taro; Aoki, Kazuhiro; Ohya, Keiichi; Jimi, Eijiro; Obata, Yuichi; Doi, Takahiro

2014-11-01

257

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

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

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

2014-10-01

258

The role of middle ear effusions and epidermal growth factor in cholesteatoma formation in the gerbilline temporal bone.  

PubMed

To study the process of aural cholesteatoma formation, we used gerbilline temporal bones to examine histologically the early stages of spontaneous cholesteatomas associated with experimentally induced otitis media with effusion (OME) following electric cauterizations of the eustachian tube. Epidermal growth factor (EGF) was then localized immunohistochemically in the pars flaccida of normal ears and the forming spontaneous cholesteatomas. Findings in the ears with the early spontaneous cholesteatomas were effusion inside the pars flaccida and hypertrophy and hyperkeratosis of the pars flaccida. Findings in the ears with experimental OME involved an effusion in the whole middle ear cavity as well as hypertrophy and hyperkeratosis in both the pars flaccida and pars tensa. The incidence of ear drum changes was higher in the experimental OME group than in control animals without cauterization. EGF was localized in the mucous layer of normal drums, the mucous layer and lamina propria of drums with hypertrophy alone, and all layers in drums with hypertrophy and hyperkeratosis. EGF was especially positive in the cytoplasms of transformed cuboidal cells. These findings suggest that EGF within the transformed mucous layer may play an important role as a biochemical factor in developing cholesteatomas. PMID:8562039

Omura, F; Makino, K; Amatsu, M; Itoh, H

1995-01-01

259

Formation of Jupiter's Core and Early Stages of Envelope Accretion  

NASA Astrophysics Data System (ADS)

We are performing calculations of the formation of Jupiter via core nucleated accretion and gas capture. The core starts as a seed body of a few hundred kilometers in radius and orbits within a swarm of planetesimals whose initial size distribution ranges from ~10 m to ~100 km. The planetesimals are immersed in a gaseous disk, representative of an early solar nebula. The evolution of the swarm of planetesimals accounts for collisions and gravitational stirring due to mutual interactions among bodies, and for migration and velocity damping due to interactions with the nebula gas. Collisions among planetesimals lead to growth and/or fragmentation, altering the size distribution of the swarm over time. Collisions of planetesimals with the seed body lead to its growth, resulting in the formation of a planetary core. Gas capture by the core leads to the accumulation of a tenuous atmosphere, which later becomes a massive envelope, increasing the size-dependent effective cross-section of the planet for planetesimals' accretion. Planetesimals that travel through the core's envelope release energy, affecting the thermal budget of the envelope, and deliver mass, affecting the opacity of the envelope. The calculation of dust opacity, which is especially important for envelope contraction, is performed self-consistently, accounting for coagulation and sedimentation of dust and small particles that are released in the envelope as passing planetesimals are ablated. We find that, in a disk of planetesimals with a surface density of about 10 g/cm2 at 5.2 AU, a one Earth mass core accumulates in less than 1e5 years, and that it takes over 1.5e6 years to accumulate a core of 3 Earth masses, when the core's geometrical cross-section is used for the accretion of planetesimals. Gas drag in the core's envelope increases the ability of the planet to accrete planetesimals. Smaller planetesimals are affected to a greater extent than are larger planetesimals. We find that the effective, envelope-enhanced cross-section leads to the growth of a core of 3 Earth masses in less than 1e5 years and of a core of 5 Earth masses in less than 2e5 years. By the time the total planet mass reaches about 6 Earth masses, the accretion rate of solids has dropped below ~1e-6 Earth masses per year. Support for this research from NASA Outer Planets Research Program is gratefully acknowledged.

D'Angelo, G.; Weidenschilling, S.; Lissauer, J. J.; Bodenheimer, P.; Hubickyj, O.

2012-12-01

260

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

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

261

Early effects of 1,25 dihydroxyvitamin D on bone calcium in vitamin D-deficient rats  

E-print Network

Early effects of 1,25 dihydroxyvitamin D on bone calcium in vitamin D-deficient rats P. J. MARIE mineralization. Vitamin-D deficient rats were labeled with 45calcium 10 to 14 days prior to treatment (experiment. In the untreated vitamin D-deficient rats of experiment 2, the rate of 45calcium loss in serum was higher than

Paris-Sud XI, Université de

262

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymerbone  

E-print Network

morphogenetic protein; Muscle; Tissue engineering Over 800,000 bone grafting procedures are performed annually, a Johnson and Johnson Company, Raynham, MA, USA Received 10 April 2003 Abstract Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives

Lu, Helen H.

263

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

PubMed Central

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

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

2013-01-01

264

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

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

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

265

Bone Response to Surface-Modified Titanium Implants: Studies on the Early Tissue Response to Implants with Different Surface Characteristics  

PubMed Central

In a series of experimental studies, the bone formation around systematically modified titanium implants is analyzed. In the present study, three different surface modifications were prepared and evaluated. Glow-discharge cleaning and oxidizing resulted in a highly stoichiometric TiO2 surface, while a glow-discharge treatment in nitrogen gas resulted in implants with essentially a surface of titanium nitride, covered with a very thin titanium oxide. Finally, hydrogen peroxide treatment of implants resulted in an almost stoichiometric TiO2, rich in hydroxyl groups on the surface. Machined commercially pure titanium implants served as controls. Scanning Auger Electron Spectroscopy, Scanning Electron Microscopy, and Atomic Force Microscopy revealed no significant differences in oxide thickness or surface roughness parameters, but differences in the surface chemical composition and apparent topography were observed. After surface preparation, the implants were inserted in cortical bone of rabbits and evaluated after 1, 3, and 6 weeks. Light microscopic evaluation of the tissue response showed that all implants were in contact with bone and had a large proportion of newly formed bone within the threads after 6 weeks. There were no morphological differences between the four groups. Our study shows that a high degree of bone contact and bone formation can be achieved with titanium implants of different surface composition and topography. PMID:24174936

Larsson Wexell, C.; Thomsen, P.; Aronsson, B.-O.; Tengvall, P.; Rodahl, M.; Lausmaa, J.; Kasemo, B.; Ericson, L. E.

2013-01-01

266

Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats.  

PubMed

Osteoporosis mainly affects postmenopausal women and older men. Gastrointestinal hormones released after meal ingestion, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP)-2, have been shown to regulate bone turnover. However, whether GLP-1, another important gastrointestinal hormone, and its analogues also have antiosteoporotic effects, especially in aged postmenopausal situation, has not been confirmed. In the present study, we evaluated the effects of the GLP-1 receptor agonist exendin-4 on ovariectomy (OVX)-induced osteoporosis in old rats. Twelve-month-old female Sprague-Dawley rats were subjected to OVX, and exendin-4 was administrated 4 weeks after the surgery and lasted for 16 weeks. Bone characters and related serum and gene biomarkers were analyzed. Sixteen weeks of treatment with exendin-4 slowed down body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats. Exendin-4 also enhanced bone strength and prevented the deterioration of trabecular microarchitecture. Moreover, exendin-4 decreased the urinary deoxypyridinoline (DPD)/creatinine ratio and serum C-terminal cross-linked telopeptides of type I collagen (CTX-I) and increased serum alkaline phosphatase (ALP), osteocalcin (OC), and N-terminal propeptide of type 1 procollagen (P1NP) levels, key biochemical markers of bone turnover. Interestingly, gene expression results further showed that exendin-4 not only inhibited bone resorption by increasing the osteoprotegerin (OPG)/receptor activator of NF-?B ligand (RANKL) ratio, but also promoted bone formation by increasing the expression of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous antiosteoporotic agents. In conclusion, these findings demonstrated for the first time the antiosteoporotic effects of exendin-4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis. PMID:23427056

Ma, Xue; Meng, Jingru; Jia, Min; Bi, Long; Zhou, Ying; Wang, Yukun; Hu, Jing; He, Gonghao; Luo, Xiaoxing

2013-07-01

267

The formation and early differentiation of the Earth  

NASA Astrophysics Data System (ADS)

The currently accepted model of planetary formation is that the cloud and dust surrounding the young sun accreted in about 104 yr to form 10 km size planetesimals. Gravitational interactions and collisions between planetesimals progressed to generate a few tens of moon to Mars-sized planetary embryos in ~1 M.yr. Earth grew from these embryos through a succession of impacts, culminating in the moon-forming giant impact. The energies of impact, combined with the energy of radioactive decay means that the growing Earth would have frequently been covered by a thick molten layer, a "Magma Ocean" which assisted in differentiation. Apart from the insight provided by these models, the principal evidence for the earliest history of the Earth comes from the chemical and isotopic compositions of the silicate mantle and crust, collectively called the "Bulk Silicate Earth"(BSE). Since the Earth has close chemical affinities with undifferentiated chondritic meteorites, the chemical and isotopic similarities and differences between BSE and undifferentiated meteorites enable us to constrain better the processes of accretion and differentiation of the early Earth. BSE is depleted in siderophile elements such as Ni, Co, Au and Pt relative to undifferentiated meteorites because these elements were partitioned into the core. We now have a large number of experimental data on how elements partition between metal and silicate which enable us to determine how Earth segregated its core. Simultaneous consideration of the depletion factors of a large number of elements in BSE lead to the following general conclusions: (1) The average pressure of core segregation on Earth was high >30 GPa , implying depths of >800 km. (2) Earth began as a small, strongly reduced body and became more oxidised as it grew. (3) Si and S are major components of the "light" element in Earth's core. Short and long-lived radionuclide systems constrain the timing of accretion and differentiation. 182 Hf (t¬¬1/2=9 M.yr) which is lithophile decays to siderophile 182W. The 182W isotope anomaly of BSE constrains the Earth to have been 90% accreted within ~25 M.yr of the origin of the solar system. The long-lived 235,238U (lithophile) - 207,206Pb (siderophile) system can only be consistent with the 182Hf-182W system, however, if Pb was lost to the core or to space at the time of the moon-forming impact 80-140 M.yr after the origin of the solar system. Crystallisation of the lower mantle led to the production of silicate perovskites of (Mg,Fe)SiO3 and CaSiO3 composition. These minerals are unusual in their affinity for elements which are not readily accommodated in the upper mantle- U, Th, Zr, Hf, Fe3+ for example. From experimentally- measured partitioning of these elements between perovskite and silicate melt we are able to show that almost all chemical evidence of an early magma ocean has been obliterated by mantle convection. The one current exception is the 142Nd (product of 146Sm decay) anomaly of the upper mantle which implies a higher than chondritic Sm/Nd ratio of BSE. Either there is a corresponding high Nd/Sm reservoir "hidden" in the Earth or some material with high Nd/Sm was lost from Earth during accretion. A final attribute of silicate perovskite is its affinity for Fe3+ which is so strong that it can force disproportionation of Fe2+ to Fe3+ plus Fe (metal). This means that the relatively high Fe3+/Fe2+ ratio of the mantle may have been internally generated by perovskite crystallisation rather than produced by recycling of oxidised Fe through subduction.

Wood, Bernard J.

2010-05-01

268

Cross-population analysis of the growth of long bones and the os coxae of three Early Medieval Austrian populations.  

PubMed

Inter-population variability in long-bone and pelvic-bone growth during the Early Medieval period is examined. The materials comprise four archaeological populations: two Slavonic (Gars-Thunau, Zwentendorf, Austria, 10th-century AD), one Avar (Zwölfaxing, Austria, 8th-century AD), and one Anglo-Saxon (Raunds, England, 10th-century AD). Bone measurements are analyzed against dental age estimates in order to assess inter-population differences in growth rates for long-bone and os coxae bone dimensions. Growth curves of the upper and lower extremities of additional archaeological populations and a modern North-American population are also assessed. The expectation was that the greatest differences in growth patterns would be found between the Anglo-Saxon and the Austrian samples, due to their distinct genetic and biocultural background. Minimal differences were expected between the two Slavonic populations, as these were approximately contemporaneous, recovered from geographically close locations, and shared relatively similar archaeological contexts. Growth curves were estimated for each bone dimension by fitting least-squares fourth-order polynomials (which allowed testing of population differences by analysis of covariance), and iteratively estimating Gompertz growth curves. The results showed differences between bones in the extent of inter-population variability, with diaphyseal long-bone growth showing equivalent patterns across the four populations, but significant differences between populations in the growth patterns of distal diaphyseal dimensions of the femur and humerus and the dimensions of the ilium. Varying growth patterns are therefore associated with inter-population differences in absolute dimensions in relation to age as well as variations in growth velocities. Inter-population variability in growth curves in the case of femoral and humeral dimensions were most pronounced during infancy (0-2 years). The most consistent differences in bone growth and related dimensions are between Zwölfaxing and the other samples. No significant differences in growth were detected between the Anglo-Saxon and the Austrian populations. PMID:15981184

Pinhasi, R; Teschler-Nicola, M; Knaus, A; Shaw, P

2005-01-01

269

The early formation of the IVA iron meteorite parent body  

NASA Astrophysics Data System (ADS)

The IVA iron meteorites are magmatic cumulates from the core of a small asteroid, which broke apart ˜ 400 Ma ago. As the depletion of this planetary body in volatile elements is expected to be reflected in high U/Pb ratios of its minerals, we embarked on analyzing the isotope composition of Pb in the cm-sized troilite inclusions of Muonionalusta and Gibeon, both iron meteorites belonging to the IVA family. The bulk of the data for nine troilite subsamples of Muonionalusta scatter with an apparent age of 4.57 Ga, which is shown to reflect the presence of both primordial and common terrestrial Pb components, in addition to radiogenic Pb. The most radiogenic subsample, however, has fractions with 206Pb/ 204Pb ratios as high as over 1000 and gives a statistically significant 207Pb*/ 206Pb* age of 4565.3 ± 0.1 Ma (MSWD = 0.08), consistent with the 182Hf- 182W metal-silicate segregation age of 2.4 ± 2.0 Ma. These data make the age of Muonionalusta the oldest documented yet for all differentiated bodies in the Solar System and constitute the first high-precision Pb-Pb age determined for crystallization of a phase contained within an iron meteorite group, hence advancing our understanding of early Solar System chronology. Using literature values for the cooling rate, and assuming a closure temperature for Pb of 300 °C, it is further estimated that the IVA parent body accreted within 1 Ma of CAI formation and had cooled to the Pb closure temperature within an additional 1-2 Ma. The overlap between the high-precision Pb-Pb and Hf-W ages points to a small, or rapidly fragmented, planetary body. The isotopic composition of Pb in Gibeon troilite yields a significantly younger age of 4544 ± 7 Ma (MSWD = 1.5), consistent with evidence from the 107Pd- 107Ag chronometer, but we believe this age has been reset by melting upon shock. One puzzling observation is that the apparent 232Th/ 238U of Muonionalusta troilite is particularly low (˜ 0.32), requiring a mechanism capable of efficiently fractionating Th from U, presumably the reduction of U to its trivalent form or the crystallization of phosphate. Average Pb concentrations of the order of 5-10 ppb and high 238U/ 204Pb ratios of > 1000 require U concentrations in troilite in the sub-ppb to one ppb range. This may indicate that troilite inclusions in IVA meteorites do not represent metal-sulfide unmixing, but rather correspond to late-stage S-rich liquid residues from extreme crystallization of the interstitial melts.

Blichert-Toft, Janne; Moynier, Frédéric; Lee, Cin-Ty A.; Telouk, Philippe; Albarède, Francis

2010-08-01

270

Enhancement of ectopic bone formation by bone morphogenetic protein-2 delivery using heparin-conjugated PLGA nanoparticles with transplantation of bone marrow-derived mesenchymal stem cells  

Microsoft Academic Search

This study was performed to determine if a combination of previously undifferentiated bone marrow-derived mesenchymal stem\\u000a cells (BMMSCs) and exogenous bone morphogenetic protein-2 (BMP-2) delivered via heparin-conjugated PLGA nanoparticles (HCPNs)\\u000a would extensively regenerate bone in vivo. In vitro testing found that the HCPNs were able to release BMP-2 over a 2-week\\u000a period. Human BMMSCs cultured in medium containing BMP-2-loaded HCPNs

Sung Eun Kim; Oju Jeon; Jung Bok Lee; Min Soo Bae; Heoung-Jae Chun; Seong-Hwan Moon; Il Keun Kwon

2008-01-01

271

PRINT ONLY: EARLY SOLAR SYSTEM EVOLUTION AND PLANETARY FORMATION Alibert Y. Mousis O.  

E-print Network

of Noble Gases by H3 + in the Outer Solar Nebula -- Implications for the Formation of Comets [#1331] We-phase for the formation of comets in the outer solar nebula. Petit J.-M. Mousis O. Alibert Y. Horner J. PhotophoresisPRINT ONLY: EARLY SOLAR SYSTEM EVOLUTION AND PLANETARY FORMATION Alibert Y. Mousis O. Structure

Rathbun, Julie A.

272

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis.  

PubMed

This study was designed to investigate the effects of local delivery of adipose-derived stem cells (ADSCs) transfected with transcription factor osterix (OSX) on bone formation during distraction osteogenesis. New Zealand white rabbits (n=54) were randomly divided into three groups (18 rabbits per group). A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the right mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density (BMD). Three parameters were measured, namely, the thickness of new trabeculae (TNT), and the volumes of the newly generated cortical bone (NBV1) and the cancellous bone (NBV2) of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo. PMID:24793766

Lai, Qing-guo; Sun, Shao-long; Zhou, Xiao-hong; Zhang, Chen-ping; Yuan, Kui-feng; Yang, Zhong-jun; Luo, Sheng-lei; Tang, Xiao-peng; Ci, Jiang-bo

2014-05-01

273

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis*  

PubMed Central

This study was designed to investigate the effects of local delivery of adipose-derived stem cells (ADSCs) transfected with transcription factor osterix (OSX) on bone formation during distraction osteogenesis. New Zealand white rabbits (n=54) were randomly divided into three groups (18 rabbits per group). A directed cloning technique was used for the construction of recombinant plasmid pEGFP-OSX, where EGFP is the enhanced green fluorescence protein. After osteodistraction of the right mandible of all experimental rabbits, rabbits in group A were treated with ADSCs transfected with pEGFP-OSX, group B with ADSCs transfected with pEGFP-N1, and group C with physiological saline. Radiographic and histological examinations were processed after half of the animals within each group were humanely killed by injection of sodium pentothal at Week 2 or 6 after surgery. The distraction bone density was measured as its projectional bone mineral density (BMD). Three parameters were measured, namely, the thickness of new trabeculae (TNT), and the volumes of the newly generated cortical bone (NBV1) and the cancellous bone (NBV2) of the distracted regions. Good bone generation in the distraction areas was found in group A, which had the highest BMD, TNT, and NBV in the distraction zones among the groups. There was no significant difference in bone generation in the distraction areas between groups B and C. The results indicate that the transplantation of ADSCs transfected with pEGFP-OSX can effectively promote bone generation during distraction in vivo. PMID:24793766

Lai, Qing-guo; Sun, Shao-long; Zhou, Xiao-hong; Zhang, Chen-ping; Yuan, Kui-feng; Yang, Zhong-jun; Luo, Sheng-lei; Tang, Xiao-peng; Ci, Jiang-bo

2014-01-01

274

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

NASA Technical Reports Server (NTRS)

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).

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

1992-01-01

275

Longitudinal Study of Bone Density and its Determinants in Women in Peri or Early Menopause  

Microsoft Academic Search

.   The evolution of bone mass across menopause as well as the factors related to bone loss were studied in 141 women already\\u000a assessed 10 years ago while in premenopause. Bone density of the lumbar spine was measured by dual photon absorptiometry.\\u000a Nutrient intakes, lifestyle habits, data on menopause, and hormone replacement therapy were obtained by questionnaires. Present\\u000a bone density

D. Picard; A. Imbach; M. Couturier; R. Lepage; L-G Ste-Marie

2000-01-01

276

Semen astragali complanati- and rhizoma cibotii-enhanced bone formation in osteoporosis rats  

PubMed Central

Background Growing evidence shows that herb medicines have some anti-osteoporotic effects, the mechanism underlying is unknown. This study aims to investigate the therapeutic effect of Chinese herb supplements on rats that had osteoporosis-like symptom induced by ovariectomy (OVX). Methods OVX or sham operations were performed on virgin Wistar rats at three-month old, which were randomly divided into eight groups: sham (sham); OVX control group (OVX); OVX rats with treatments [either diethylstilbestrol (DES) or Semen Astragali Complanati decoction (SACD) or Rhizoma Cibotii decoction (RCD) or Herba Cistanches decoction (HCD) or Semen Allii Tuberosi decoction (SATD)]. Non-surgical rats were served as a normal control (NC). The treatments began 4 weeks after surgery, and lasted for 12 weeks. Bone mass and its turnover were analyzed by histomorphometry. Levels of protein and mRNA of osteoprotegerin (OPG) and receptor activator of nuclear factor ?B ligand (RANKL) in osteoblasts (OB) and bone marrow stromal cells (bMSC) were evaluated by immunohistochemistry and in situ hybridization. Results Compared to OVX control, TBV% in both SACD and RCD groups was increased significantly, while TRS%, TFS%, MAR, and mAR were decreased remarkably in the SACD group, only TRS% decreased dramatically in the RCD group. No significant changes in bone formation were observed in either HCD or SATD groups. OPG levels in both protein and mRNA were reduced consistantly in OB and bMSC from OVX control rats, in contrast, RANKL levels in both protein and mRNA were increased significantly. These effects were substantially reversed by treatments with either DES or SACD or RCD. No significant changes in both OPG and RANKL expression were observed in OB and bMSC from OVX rats treated with SATD and HCD. Conclusions Our study showed that SACD and RCD increased bone formation by stimulating OPG expression and downregulating RANKL expression in OB and bMSC. This suggests that SACD and RCD may be developed as alternative anti-osteoporotic agents for therapy of postmenopausal osteoporosis. PMID:23782721

2013-01-01

277

Living Arrangements and Family Formation Attitudes in Early Adulthood.  

ERIC Educational Resources Information Center

Examines the impact of nonfamily living arrangements and cohabitation on changes in family formation attitudes at the individual level. Results indicate that both the experience and duration of cohabiting arrangements have significant effects on family formation attitudes but fail to show significant consequences of premarital, nonfamily living…

Axinn, William G.; Barber, Jennifer S.

1997-01-01

278

Uncoupling of growth plate maturation and bone formation in mice lacking both Schnurri-2 and Schnurri-3  

PubMed Central

Formation and remodeling of the skeleton relies on precise temporal and spatial regulation of genes expressed in cartilage and bone cells. Debilitating diseases of the skeletal system occur when mutations arise that disrupt these intricate genetic regulatory programs. Here, we report that mice bearing parallel null mutations in the adapter proteins Schnurri2 (Shn2) and Schnurri3 (Shn3) exhibit defects in patterning of the axial skeleton during embryogenesis. Postnatally, these compound mutant mice develop a unique osteochondrodysplasia. The deletion of Shn2 and Shn3 impairs growth plate maturation during endochondral ossification but simultaneously results in massively elevated trabecular bone formation. Hence, growth plate maturation and bone formation can be uncoupled under certain circumstances. These unexpected findings demonstrate that both unique and redundant functions reside in the Schnurri protein family that are required for proper skeletal patterning and remodeling. PMID:20404140

Jones, Dallas C.; Schweitzer, Michelle N.; Wein, Marc; Sigrist, Kirsten; Takagi, Tsuyoshi; Ishii, Shunsuke; Glimcher, Laurie H.

2010-01-01

279

Modulation of early functional recovery of Achilles tendon to bone unit after transection by BPC 157 and methylprednisolone  

Microsoft Academic Search

.\\u000a Objective and design:  In the presented study we compared the effect of stable peptide BPC 157 and methylprednisolone on early functional recovery\\u000a after Achilles tendon to bone transection in a rat model before collagen healing started.\\u000a \\u000a \\u000a \\u000a Material and methods:  Surgical transection of the right Achilles tendon to bone area was performed in seventy two Wistar Albino male rats. Healing\\u000a Achilles tendon

A. Krivic; M. Majerovic; I. Jelic; S. Seiwerth; P. Sikiric

2008-01-01

280

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

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

2013-01-01

281

Early detection of delayed union in lower leg fractures using a computerised analysis of mechanical vibration reactions of bone for assessing the state of fracture healing.  

PubMed

Standard X-ray techniques are used to follow up the healing process of bone fractures. However, these methods allow only indirect conclusions about the stability of the healing bone, depending on the experience of the clinician. In addition, by radiologic means, delayed union or non-union can only be diagnosed on the basis of the absence of specific changes such as callus formation. Therefore, efforts have been made to develop alternative methods for monitoring the healing process. The measuring principle of a non-invasive method is based on evaluation of changes in mechanical vibration reactions. The measuring system is composed of two sound transducers, an amplifier module and an AD converter attached to a PC. The assessment of 150 healthy individuals as well as an initial measuring series after treatment of tibial fractures with an external fixator system revealed highly significant differences between intact and fractured tibias. Thus, computerised sonometry is capable of supplying quantitatively recordable information about the stability of a fractured bone at any time in the healing process. Furthermore, this non-invasive technique allows early diagnosis of disorders in the repair process by the absence of change in the parameters. PMID:8186056

Fellinger, M; Leitgeb, N; Szyszkowitz, R; Peicha, G; Passler, J; Seggl, W; Schanner, A

1994-01-01

282

Optimisation of the differing conditions required for bone formation in vitro by primary osteoblasts from mice and rats  

PubMed Central

The in vitro culture of calvarial osteoblasts from neonatal rodents remains an important method for studying the regulation of bone formation. The widespread use of transgenic mice has created a particular need for a reliable, simple method that allows the differentiation and bone-forming activity of murine osteoblasts to be studied. In the present study, we established such a method and identified key differences in optimal culture conditions between mouse and rat osteoblasts. Cells isolated from neonatal rodent calvariae by collagenase digestion were cultured for 14–28 days before staining for tissue non-specific alkaline phosphatase (TNAP) and bone mineralisation (alizarin red). The reliable differentiation of mouse osteoblasts, resulting in abundant TNAP expression and the formation of mineralised ‘trabecular-shaped’ bone nodules, occurred only following culture in ? minimum essential medium (?MEM) and took 21–28 days. Dexamethasone (10 nM) inhibited bone mineralisation in the mouse osteoblasts. By contrast, TNAP expression and bone formation by rat osteoblasts were observed following culture in both ?MEM and Dulbecco’s modified Eagle’s medium (DMEM) after approximately 14 days (although ~3-fold more effectively in ?MEM) and was strongly dependent on dexamethasone. Both the mouse and rat osteoblasts required ascorbate (50 ?g/ml) for osteogenic differentiation and ?-glycerophosphate (2 mM) for mineralisation. The rat and mouse osteoblasts showed similar sensitivity to the well-established inhibitors of mineralisation, inorganic pyrophosphate (PPi) and adenosine triphosphate (ATP; 1–100 ?M). The high efficiency of osteogenic differentiation observed following culture in ?MEM, compared with culture in DMEM possibly reflects the richer formulation of the former. These findings offer a reliable technique for inducing mouse osteoblasts to form bone in vitro and a more effective method for culturing bone-forming rat osteoblasts. PMID:25200658

ORRISS, ISABEL R.; HAJJAWI, MARK O.R.; HUESA, CARMEN; MACRAE, VICKY E.; ARNETT, TIMOTHY R.

2014-01-01

283

Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis.  

PubMed

Studies have demonstrated the important role of bone remodelling and osteoimmunology in the progression of inflammatory lesions in axial spondyloarthritis (SpA) disease. This study was conducted to evaluate the inflammatory response by analysis of the serum levels of pro-inflammatory and new bone formation markers in patients with axial SpA who were treated or not treated with anti-tumour necrosis factor-? (anti-TNF-?) or non-steroidal drugs (NSAIDs) and to identify whether these drugs modify the activity and severity of the disease. The serum levels of myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), bone alkaline phosphatase (BAP), Dickkopf-1 (DKK-1), and osteoprotegerin (OP) were measured in 52 SpA patients who were treated or not with anti-TNF-? or NSAIDs and in 26 healthy controls using colourimetric and enzyme immunoassay tests. The activity and the severity of illness in patients with SpA were assessed using questionnaires (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). A significant difference between the controls and the patients without medication was observed in relation to NOx, BAP, and OP (p<0.01). When the patients were compared with regard to their treatment, there were no clinically significant differences between the groups (p>0.05). In conclusion, The NOx, BAP, and OP are emerging as important inflammatory pathways in axial SpA. Also the anti-TNF-? or non-steroidal drugs reduce the inflammation and destructions, however these treatments do not modify the serum levels of these biomarkers. PMID:24925756

de Andrade, Kenia Rodrigues; de Castro, Gláucio Ricardo Werner; Vicente, Geison; da Rosa, Julia Salvan; Nader, Marina; Pereira, Ivanio Alves; Fröde, Tânia Silvia

2014-08-01

284

Thai traditional massage increases biochemical markers of bone formation in postmenopausal women: a randomized crossover trial  

PubMed Central

Background The effect of massage therapy on bone metabolism in adults has only scarcely been explored. In a randomized crossover trial, we investigated the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover. Methods Forty-eight postmenopausal women participated in the study. All volunteers were randomized to a 2-hour session of Thai traditional massage twice a week for 4 weeks and a 4-week control period after a 2-week washout, or vice versa. Twenty-one subjects were allocated to receiving Thai traditional massage first, followed by the control period, while 27 were initially allocated to the control period. Results Serum P1NP increased significantly after Thai traditional massage (P <0.01), while there was no change in serum osteocalcin or CTX. During the control period, there was no significant change in P1NP, osteocalcin or CTX compared to baseline. When age and height were taken into account, P1NP in postmenopausal women whose ages were in the middle and higher tertiles and whose heights were in the lower and middle tertiles (n = 22) had a 14.8 ± 3.3% increase in P1NP after massage (P <0.001), while no change in P1NP was found in the rest of the women (n = 26). Conclusions Thai traditional massage results in an increase in bone formation as assessed by serum P1NP, particularly in postmenopausal women who are older and have a smaller body build. Future studies with larger samples and additional design features are warranted. Trial registration ClinicalTrials.gov : NCT01627028 PMID:23530566

2013-01-01

285

Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and evaluation of its efficacy on peri-implant bone formation.  

PubMed

Dental implant insertion on a site with low bone quality or bone defect should be preceded by a bone graft or artificial bone graft insertion to heal the defect. We generated a beta-tricalcium phosphate (?-TCP) and poloxamer 407-based hydrogel composite and penetration of the ?-TCP/hydrogel composite into the peri-implant area of bone was evaluated by porous bone block experiments. The maximum penetration depth for porous bone blocks and dense bone blocks were 524??m and 464??m, respectively. We report the in-vivo performance of a composite of ?-TCP/hydrogel composite as a carrier of recombinant human bone morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model. Three holes drilled into each tibia of eight male rabbits were (1) grafted with dental implant fixtures; (2) filled with ?-TCP/hydrogel composite (containing 5??g of rhBMP-2), followed by grafting of the dental implant fixtures. Four weeks later, bone-implant contact ratio and peri-implant bone formation were analyzed by radiography, micro-CT and histology of undecalcified specimens. The micro-CT results showed a significantly higher level of trabecular thickness and new bone and peri-implant new bone formation in the experimental treatment compared to the control treatment. Histomorphometry revealed a significantly higher bone-implant contact ratio and peri-implant bone formation with the experimental treatment. The use of ?-TCP/poloxamer 407 hydrogel composite as a carrier of rhBMP-2 significantly promoted new bone formation around the dental implant fixture and it also improved the quality of the new bone formed in the tibial marrow space. PMID:25135209

Lee, Jae Hyup; Ryu, Mi Young; Baek, Hae-Ri; Seo, Jun-Hyuk; Lee, Kyung-Mee; Lee, Ji-Ho

2014-10-01

286

Bio-activated titanium surface utilizable for mimetic bone implantation in dentistry—Part III: Surface characteristics and bone implant contact formation  

NASA Astrophysics Data System (ADS)

This study was carried out to quantify the effect of an alkali-modified surface on the bone implant interface formation during healing using an animal model. A total of 24 screw-shaped, self-tapping, (c.p.) titanium dental implants, divided into test group B—implants with alkali-modified surface (Bio surface) and control group M—implants with turned, machined surface, were inserted without pre-tapping in the tibiae of three beagle dogs. The animals were sacrificed after 2, 5 and 12 weeks and the bone implant contact (BIC%) was evaluated histometrically. The surface characteristics that differed between the implant surfaces, i.e. specific surface area, contact angle, may represent factors that influence the rate of osseointegration and the secondary implant stability. The alkali-treated surface enhances the BIC formation during the first 2 5 weeks of healing compared to the turned, machined surface.

Strnad, Jakub; Strnad, Zden?k; Šesták, Jaroslav; Urban, Karel; Povýšil, Ctibor

2007-05-01

287

The Mesenchymal Stem Cell Marker CD248 (Endosialin) Is a Negative Regulator of Bone Formation in Mice  

PubMed Central

Objective CD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248-knockout (CD248?/?) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass. Methods Western blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro-computed tomography and the 3-point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10-week-old wild-type (WT) or CD248?/? mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM ?-glycerophosphate and 50 ?g/ml ascorbic acid to induce mineralization, and then treated with platelet-derived growth factor BB (PDGF-BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling. Results Expression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248?/? mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248?/? mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF-BB, which could be attributed to a defect in PDGF signal transduction in the CD248?/? mice. Conclusion There is an unmet clinical need to address rheumatoid arthritis–associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast-mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation. PMID:22674221

Naylor, Amy J.; Azzam, Eman; Smith, Stuart; Croft, Adam; Poyser, Callum; Duffield, Jeremy S.; Huso, David L.; Gay, Steffen; Ospelt, Caroline; Cooper, Mark S.; Isacke, Clare; Goodyear, Simon R.; Rogers, Michael J.; Buckley, Christopher D.

2014-01-01

288

Organism-scale modeling of early Drosophila patterning via Bone Morphogenetic Proteins  

PubMed Central

Advances in image acquisition and informatics technology have led to organism-scale spatio-temporal atlases of gene expression and protein distributions. To maximize the utility of this information for the study of developmental processes, a new generation of mathematical models is needed for discovery and hypothesis testing. Here we develop a data-driven, geometrically-accurate, model of early Drosophila embryonic bone morphogenetic protein (BMP)-mediated patterning. We tested nine different mechanisms for signal transduction with feedback, eight combinations of geometry and gene expression prepatterns, and two scale-invariance mechanisms for their ability to reproduce proper BMP signaling output in wild-type and mutant embryos. We found that a model based on positive feedback of a secreted BMP binding protein, coupled with the experimentally-measured embryo geometry, provides the best agreement with population-mean image data. Our results demonstrate that using bioimages to build and optimize a 3D model provides significant new insights into mechanisms that guide tissue patterning. PMID:20159596

Umulis, David M.; Shimmi, Osamu; O'Connor, Michael B.; Othmer, Hans G.

2010-01-01

289

A computational model of clavicle bone formation: a mechano-biochemical hypothesis.  

PubMed

Clavicle development arises from mesenchymal cells condensed as a cord extending from the acromion towards the sternal primordium. First two primary ossification centers form, extending to develop the body of the clavicle through intramembranous ossification. However, at its ends this same bone also displays endochondral ossification. So how can the clavicle be formed by both types of ossification? Developmental events associated with clavicle formation have mainly used histological studies as supporting evidence. Nonetheless, mechanisms of biological events such as molecular and mechanical effects remain to be determined. The objective of this work was to provide a mathematical explanation of embryological events based on two serial phases: first formation of an ossified matrix by intramembranous ossification based on three factors: systemic, local biochemical, and mechanical factors. After this initial phase expansion of the ossified matrix follows with mesenchymal cell differentiation into chondrocytes for posterior endochondral ossification. Our model provides strong evidence for clavicle formation integrating molecules and mechanical stimuli through partial differentiation equations using finite element analysis. PMID:24444803

Garzon-Alvarado, Diego A; Gutiérrez, María Lucía; Calixto, Luis Fernando

2014-04-01

290

Evidence for estrogen receptor expression during medullary bone formation and resorption in estrogen-treated male Japanese quails (Coturnix coturnix japonica).  

PubMed

The temporal expression of estrogen receptor (ER)-? and ER-? mRNA was examined in male Japanese quails. Femurs of quails receiving 17?-estradiol underwent RT-PCR and histochemical analysis 1 to 15 days after treatment. Untreated quails were used as controls (day 0). Between days 0 and 5, cells lining the bone endosteal surface differentiated into osteoblasts, which in turn formed medullary bone. Expression of ER-? was already observed on day 0 and increased slightly during bone formation whereas ER-? was hardly detected throughout this process. After osteoclasts appeared on the medullary bone surface, this type of bone disappeared from the bone marrow cavity (days 7˜15). ER-? expression simultaneously decreased slightly and ER-? levels remained very low. These results suggest that estrogen activity mediated by ER-? not only affects medullary bone formation but also bone resorption. PMID:23000578

Hiyama, Shinji; Sugiyama, Toshie; Kusuhara, Seiji; Uchida, Takashi

2012-09-01

291

Evidence for estrogen receptor expression during medullary bone formation and resorption in estrogen-treated male Japanese quails (Coturnix coturnix japonica)  

PubMed Central

The temporal expression of estrogen receptor (ER)-? and ER-? mRNA was examined in male Japanese quails. Femurs of quails receiving 17?-estradiol underwent RTPCR and histochemical analysis 1 to 15 days after treatment. Untreated quails were used as controls (day 0). Between days 0 and 5, cells lining the bone endosteal surface differentiated into osteoblasts, which in turn formed medullary bone. Expression of ER-? was already observed on day 0 and increased slightly during bone formation whereas ER-? was hardly detected throughout this process. After osteoclasts appeared on the medullary bone surface, this type of bone disappeared from the bone marrow cavity (days 7~15). ER-? expression simultaneously decreased slightly and ER-? levels remained very low. These results suggest that estrogen activity mediated by ER-? not only affects medullary bone formation but also bone resorption. PMID:23000578

Sugiyama, Toshie; Kusuhara, Seiji; Uchida, Takashi

2012-01-01

292

Molecular gas and star formation in early-type galaxies  

NASA Astrophysics Data System (ADS)

We present new mm interferometric and optical integral-field unit (IFU) observations and construct a sample of 12 elliptical (E) and lenticular (S0) galaxies with molecular gas which have both CO and optical maps. The galaxies contain 2 × 107 to 5 × 109 M? of molecular gas distributed primarily in central discs or rings (radii 0.5-4 kpc). The molecular gas distributions are always coincident with distributions of optically obscuring dust that reveal tightly wound spiral structures in many cases. The ionized gas always approximately corotates with the molecular gas, evidencing a link between these two gas components, yet star formation is not always the dominant ionization source. The galaxies with less molecular gas tend to have [O III]/H? emission-line ratios at high values not expected for star formation. Most E/S0s with molecular gas have young or intermediate-age stellar populations based on optical colours, ultraviolet colours and absorption linestrengths. The few that appear purely old lie close to the limit where such populations would be undetectable based on the mass fractions of expected young to observed old stars. The 8 ?m polycyclic aromatic hydrocarbon (PAH) and 24 ?m emission yield similar star formation rate (SFR) estimates of E/S0s, but the total infrared overpredicts the rate due to a contribution to dust heating from older stars. The radio-far-infrared relation also has much more scatter than for other star-forming galaxies. However, despite these biases and additional scatter, the derived star formation rates locate the E/S0 galaxies within the large range of the Schmidt-Kennicutt and constant efficiency star formation laws. Thus, the star formation process in E/S0s is not overwhelmingly different than in other star-forming galaxies, although one of the more reliable tracers (24 ?m) points to a possible lower star formation efficiency at a given gas surface density.

Crocker, Alison F.; Bureau, Martin; Young, Lisa M.; Combes, Francoise

2011-01-01

293

Lower peak bone mass and abnormal trabecular and cortical microarchitecture in young men infected with HIV early in life  

PubMed Central

Introduction HIV infection and antiretroviral therapy (ART) early in life may interfere with acquisition of peak bone mass, thereby increasing fracture risk in adulthood. Methods We conducted a cross-sectional study of dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) in 30 HIV-infected African–American or Hispanic Tanner stage 5 men aged 20–25 on ART (15 perinatally infected and 15 infected during adolescence) and 15 HIV-uninfected controls. Results HIV-infected men were similar in age and BMI, but were more likely to be African–American (P = 0.01) than uninfected men. DXA-derived areal bone mineral density (aBMD) Z-scores were 0.4–1.2 lower in HIV-infected men at the spine, hip, and radius (all P < 0.05). At the radius and tibia, total and trabecular volumetric BMD (vBMD), and cortical and trabecular thickness were between 6 and 19% lower in HIV-infected than uninfected men (P <0.05). HIV-infected men had dramatic deficiencies in plate-related parameters by individual trabeculae segmentation (ITS) analyses and 14–17% lower bone stiffness by finite element analysis revealed. Differences in most HR-pQCT parameters remained significant after adjustment for race/ethnicity. No DXA or HR-pQCT parameters differed between men infected perinatally or during adolescence. Conclusion At an age by which young men have typically acquired peak bone mass, HIV-infected men on ART have lower BMD, markedly abnormal trabecular plate and cortical microarchitecture, and decreased whole bone stiffness, whether infected perinatally or during adolescence. Reduced bone strength in young adults infected with HIV early in life may place them at higher risk for fractures as they age. PMID:24072196

Yin, Michael T.; Lund, Emily; Shah, Jayesh; Zhang, Chiyuan A.; Foca, Marc; Neu, Natalie; Nishiyama, Kyle K.; Zhou, Bin; Guo, Xiangdong E.; Nelson, John; Bell, David L.; Shane, Elizabeth; Arpadi, Stephen M.

2014-01-01

294

Early microbial biofilm formation on marine plastic debris  

Microsoft Academic Search

An important aspect of the global problem of plastic debris pollution is plastic buoyancy. There is some evidence that buoyancy is influenced by attached biofilms but as yet this is poorly understood. We submerged polyethylene plastic in seawater and sampled weekly for 3weeks in order to study early stage processes. Microbial biofilms developed rapidly on the plastic and coincided with

Delphine Lobelle; Michael Cunliffe

2011-01-01

295

Early Oligocene initiation of North Atlantic Deep Water formation  

Microsoft Academic Search

Dating the onset of deep-water flow between the Arctic and North Atlantic oceans is critical for modelling climate change in the Northern Hemisphere and for explaining changes in global ocean circulation throughout the Cenozoic era (from about 65 million years ago to the present). In the early Cenozoic era, exchange between these two ocean basins was inhibited by the Greenland-Scotland

Richard Davies; Joseph Cartwright; Jennifer Pike; Charles Line

2001-01-01

296

Disappearance and formation rates of microaneurysms in early diabetic retinopathy.  

PubMed Central

AIM: To analyse the formation and disappearance rates of individual microaneurysms in mild background retinopathy. METHODS: Three fluorescein angiograms were taken at 1 year intervals during a 2 year follow up from 24 type 1 diabetics with mild background retinopathy. Microaneurysms were identified and localised twice from each angiogram using a computerised system for retrieval of the coordinates for each microaneurysm. Microaneurysms identified similarly in both sessions were then processed further to obtain rates of microaneurysm formation and disappearance, and microaneurysm count changes. RESULTS: In the whole material the total number of microaneurysms increased from 298 to 436 from baseline to 2 years. During the 2 year follow up 395 new microaneurysms formed and 258 microaneurysms disappeared. Of the microaneurysms present at baseline 174 (58%) were still present at the 1 year and 142 (48%) at the 2 year follow up. In patients with good glucose control (HbA1c < or = 7.5 mmol) microaneurysm formation showed a trend of being decreased whereas microaneurysm disappearance did not correlate with glucose control. CONCLUSION: Background diabetic retinopathy is a dynamic process. A significant proportion of microaneurysms present disappear within 2 years. This is compensated for by formation of new microaneurysms, the resultant net changes in microaneurysm counts being small. Microaneurysm formation and disappearance rates are new variables of diabetic retinopathy and may prove to be more sensitive indicators of the progression patterns of background diabetic retinopathy than microaneurysm count changes. Images PMID:8814743

Hellstedt, T; Immonen, I

1996-01-01

297

Effects of cigarette smoke inhalation and coffee consumption on bone formation and osseous integration of hydroxyapatite implant.  

PubMed

The present study aims to assess the effects of cigarette smoke inhalation and/or coffee consumption on bone formation and osseous integration of a dense hydroxyapatite (DHA) implant in rats. For this study, 20 male rats were divided into four groups (n = 5): CT (control) group, CE (coffee) group, CI (cigarette) group and CC (coffee + cigarette) group. During 16 weeks, animals in the CI group were exposed to cigarette smoke inhalation equivalent to 6 cigarettes per day; specimens in the CE group drank coffee as liquid diet; and rats in the CC group were submitted to both substances. In the 6th week a 5 mm slit in the parietal bone and a 4 mm slit in the tibia were performed on the left side: the former was left open while the latter received a DHA implant. As soon as surgeries were finished, the animals returned to their original protocols and after 10 weeks of exposure they were euthanised (ethically sacrificed) and the mentioned bones collected for histological processing. Data showed that exposure to cigarette smoke inhalation and coffee consumption did not interfere in weight gain and that solid and liquid diet consumption was satisfactory. Rats in the CC group showed a decrease in bone neoformation around the tibial DHA implant (31.8 ± 2.8) as well as in bone formation in the parietal slit (28.6 ± 2.2). On their own, cigarette smoke inhalation or coffee consumption also led to diminished bone neoformation around the implant and delayed the bone repair process in relation to the CT group. However, reduction in the bone repair process was accentuated with exposure to both cigarette smoke inhalation and coffee consumption in this study. PMID:23644799

Andrade, A R; Sant'Ana, D C M; Mendes, J A; Moreira, M; Pires, G C; Santos, M P; Fernandes, G J M; Nakagaki, W R; Garcia, J A D; Lima, C C; Soares, E A

2013-02-01

298

Early Archean stromatolites: Paleoenvironmental setting and controls on formation  

NASA Technical Reports Server (NTRS)

The earliest record of terrestrial life is contained in thin, silicified sedimentary layers within enormously thick, predominantly volcanic sequences in South Africa and Western Australia. This record includes bacteria-like microfossils, laminated carbonaceous structures resembling flat bacterial mats and stromatolites, and a morphologically diverse assemblage of carbonaceous particles. These structures and particles and their host sediments provide the only direct source of information on the morphology, paleoecology, and biogeochemistry of early life; the nature of interactions between organisms and surface systems on the early earth; and possible settings within which life might have evolved. The three known occurrences of 3.5 to 3.2 billion-year-old stromalites were evaluated in terms of depositional setting and biogenicity.

Lowe, D. R.

1991-01-01

299

Orbital stability during the early stages of planetary formation  

Microsoft Academic Search

One theory of planetary formation suggests that the planets evolved from giant gaseous protoplanets which lost their volatile elements. Analytical calculations of the hierarchical stability of three-body systems suggest that the most likely configuration to be unstable is that of a large protoplanet moving in close proximity to a forming terrestrial planet which has already lost most of its excess

J. R. Donnison; I. P. Williams

1985-01-01

300

Early complications of medial opening wedge high tibial osteotomy using autologous tricortical iliac bone graft and T-plate fixation  

Microsoft Academic Search

Despite several advantages of medial opening wedge high tibial osteotomy, this procedure has been noted to have a high rate of complications especially with the use of a spacer plate for fixation. We retrospectively evaluated the early complications of 138 medial opening wedge high tibial osteotomies done using autologous tricortical iliac bone graft and T-plate fixation(AO locking compression T-plate, Ti\\/3H

Dong Ju Chae; Gautam M. Shetty; Kook Hyun Wang; Antonio Santa Cruz Montalban Jr; Jong In Kim; Kyung Wook Nha

2011-01-01

301

Metadata of the chapter that will be visualized online Chapter Title Earth, Formation Early Evolution  

E-print Network

to test ideas to be used in the search for life elsewhere in 28 the Solar System and beyond that this planet is the singular known 31 repository of life. Studies of the origin and early evolution 32 of EarthMetadata of the chapter that will be visualized online Chapter Title Earth, Formation Early

Mojzsis, Stephen J.

302

The early formation of the IVA iron meteorite parent body Janne Blichert-Toft a,  

E-print Network

The early formation of the IVA iron meteorite parent body Janne Blichert-Toft a, , Frédéric Moynier chronology absolute age IVA iron meteorites troilite cooling rate early Solar System least-square The IVA of Muonionalusta and Gibeon, both iron meteorites belonging to the IVA family. The bulk of the data for nine

Lee, Cin-Ty Aeolus

303

In vitro and in vivo evaluation of bone formation using solid freeform fabrication-based bone morphogenic protein-2 releasing PCL/PLGA scaffolds.  

PubMed

The aim of this study was to develop novel polycaprolactone/poly(lactic-co-glycolic acid) (PCL/PLGA) scaffolds with a heparin-dopamine (Hep-DOPA) conjugate for controlled release of bone morphogenic protein-2 (BMP-2) to enhance osteoblast activity in vitro and also bone formation in vivo. PCL/PLGA scaffolds were prepared by a solid freeform fabrication method. The PCL/PLGA scaffolds were functionalized with Hep-DOPA and then BMP-2 was sequentially coated onto the Hep-DOPA/PCL/PLGA scaffolds. The characterization and surface elemental composition of all scaffolds were evaluated by scanning electron microscope and x-ray photoelectron spectroscopy. The osteoblast activities on all scaffolds were assessed by cell proliferation, alkaline phosphatase (ALP) activity and calcium deposition in vitro. To demonstrate bone formation in vivo, plain radiograph, micro-computed tomography (micro-CT) evaluation and histological studies were performed after the implantation of all scaffolds on a rat femur defect. Hep-DOPA/PCL/PLGA had more controlled release of BMP-2, which was quantified by enzyme-linked immunosorbent assay, compared with Hep/PCL/PLGA. The in vitro results showed that osteoblast-like cells (MG-63 cells) grown on BMP-2/Hep-DOPA/PCL/PLGA had significantly enhanced ALP activity and calcium deposition compared with those on BMP-2/Hep/PCL/PLGA and PCL/PLGA. In addition, the plain radiograph, micro-CT evaluation and histological studies demonstrated that the implanted BMP-2/Hep-DOPA/PCL/PLGA on rat femur had more bone formation than BMP-2/Hep/PCL/PLGA and PCL/PLGA in vivo. PMID:24518200

Kim, Tae-Hoon; Yun, Young-Pil; Park, Young-Eun; Lee, Suk-Ha; Yong, Woonjae; Kundu, Joydip; Jung, Jin Woo; Shim, Jin-Hyung; Cho, Dong-Woo; Kim, Sung Eun; Song, Hae-Ryong

2014-04-01

304

Long-Term Symptoms Onset and Heterotopic Bone Formation around a Total Temporomandibular Joint Prosthesis: a Case Report  

PubMed Central

ABSTRACT Background The literature on total alloplastic temporomandibular joint (TMJ) reconstructions is encouraging, and studies on total alloplastic TMJ replacements outcomes showed acceptable improvements in terms of both pain levels and jaw function. Nevertheless, some adverse events, such as heterotopic bone formation around the implanted prosthesis, may occur. In consideration of that, the present manuscript describes a case of heterotopic bone formation around a total temporomandibular joint prosthesis, which occurred several years after the implant. Methods The present manuscript describes a case of heterotopic bone formation around a total TMJ prosthesis, which occurred several years after the implant in patients, who previously underwent multiple failed TMJ surgeries. Results Ten years after the surgical TMJ replacement to solve an ankylotic bone block, the patient came to our attention again referring a progressive limitation in mouth opening. A computerized tomography showed evidence of marked heterotopic bone formation in the medial aspects of the joint, where a new-born ankylotic block occupied most part of the gap created by resecting the coronoid process at the time of the TMJ prosthesis insertion. Conclusions Despite this adverse event has been sometimes described in the literature, this is the first case in which its occurrence happened several years after the temporomandibular joint replacement. It can be suggested that an accurate assessment of pre-operative risk factors for re-ankylosis (e.g., patients with multiple failed temporomandibular joint surgeries) and within-intervention prevention (e.g., strategies to keep the bone interfaces around the implant separated) should be better standardized and define in future studies. PMID:24800055

Guarda-Nardini, Luca; Manfredini, Daniele; Ferronato, Giuseppe

2014-01-01

305

Slope sedimentation associated with a vertically building shelf, Bone Spring Formation, Mescalero Escarpe Field, southeast New Mexico  

Microsoft Academic Search

Mescalero Escarpe field contains slope strata in the Bone Spring formation which provide insight into development of the Northwestern shelf to the north and the Delaware basin to the south. During the Leonardian (Permian), the Northwestern shelf grew vertically due to regional subsidence and cyclic sedimentation. Slope facies include (1) dolomitized peloid-bioclast packstone, (2) dolomite megabreccia, (3) laminated dolomitic mudstone,

A. H. Saller; J. W. Barton; R. E. Barton

1987-01-01

306

The Early Onset of Asymmetric Outflow During the Planetary Nebula Formation Process  

NASA Astrophysics Data System (ADS)

We propose to study early mass loss in the planetary nebula {PN} formation process using the high resolution imaging capabilities of HST. While tremendous progress has been made in understanding the late stages of PN formation, the details of the earliest phases of this metamorphosis are still vague. A knowledge of the characteristics of the mass loss occurring as a star leaves the asymptotic giant branch {AGB} is crucial to a complete picture of the PN development, since early mass loss is thought to determine the final shape of an object by confining the faster winds that occur later in the formation process. Unfortunately, there is little observational evidence that probes the distribution of this early ejecta. Is the final morphology of a PN imprinted at early times as suggested by the formation models? Fully developed PNe display a variety of morphologies ranging from round to bipolar. Based on the formation models we might expect material ejected early in the development of a PN to also exhibit a range of morphologies. Is this what we observe? We will directly address these questions by obtaining PC2 images of a sample of AGB/post-AGB stars. We have shown, using polarimetry, that the stars in this sample possess extended scattering envelopes that are spatially unresolved from the ground, but can be resolved using HST. These observations will reveal the morphology of the ejecta in the first stages of the PN formation process, thus testing the validity of the current models of PN formation.

Trammell, Susan

1996-07-01

307

IFN? impairs extracellular matrix formation leading to inhibition of mineralization by effects in the early stage of human osteoblast differentiation.  

PubMed

Osteoimmunology is an emerging field of research focused on the interaction of the immune system and bone. In this study we demonstrate that human osteoblasts are sensitive to the immune cytokine interferon (IFN)?. Osteoblasts respond to IFN? as shown by the induction of several known IFN target genes such as interferon-induced (IFI) proteins (IFIT1, IFI44L), interferon-stimulated gene factor 3 (ISGF3) complex and the induction of IFN? itself. We demonstrated that IFN? has severe inhibitory effects on mineralization of osteoblast-derived extracellular matrix (ECM). Analysis of the timing of the IFN? effects revealed that committed osteoblasts in early stage of differentiation are most sensitive to IFN? inhibition of mineralization. A single IFN? treatment was as effective as multiple treatments. During the progress of differentiation osteoblasts become desensitized for IFN?. This pinpoints to a complex pattern of IFN? sensitivity in osteoblasts. Focusing on early osteoblasts, we showed that IFN? decreased gene expression of ECM-related genes, such as type I Collagen (COL1A1), fibronectin (FN1), fibullin (FBLN1), fibrillin (FBN2), and laminin (LAMA1). Additionally, ECM produced by IFN?-treated osteoblasts contained less collagen protein. IFN? stimulated gene expression of osteopontin (OPN), annexin2 (ANXA2), and hyaluronan synthase 1 (HAS1), which are important factors in the adhesion of hematopoietic stem cells (HSC) in the HSC niche. In conclusion, IFN? directly modifies human osteoblast function by inhibiting ECM synthesis eventually resulting in delayed bone formation and mineralization and induces a HSC niche supporting phenotype. These effects are highly dependent on timing of treatment in the early phase of osteoblast differentiation. PMID:21898404

Woeckel, V J; Eijken, M; van de Peppel, J; Chiba, H; van der Eerden, B C J; van Leeuwen, J P T M

2012-06-01

308

Royal jelly stimulates bone formation: physiologic and nutrigenomic studies with mice and cell lines.  

PubMed

Royal jelly (RJ) has diverse physiological and pharmacological functions. We observed its weak estrogenic activity in the previous study. RJ stimulated the proliferation of mouse osteoblast-like MC3T3-E1 cells at 0.1 mg/ml, and the effect was blocked by the specific estrogen receptor antagonist ICI 182,780. The addition of 0.1-1.0 mg/ml RJ enhanced collagen production in culture medium. Oral administration of RJ to normal female mice for 9 weeks increased the ash content of their tibiae. DNA microarray analysis revealed significant changes in gene expression related to extracellular matrix formation when the femurs of mice fed RJ were analyzed. Quantitative reverse transcriptase-PCR (RT-PCR) confirmed up-regulation of procollagen I alpha1 gene expression. These data suggest that RJ as a whole or some of its individual components stimulates production of type I collagen and other activities for bone formation through action on osteoblasts. PMID:17031045

Narita, Yukio; Nomura, Johji; Ohta, Shozo; Inoh, Yoshikazu; Suzuki, Kazu-Michi; Araki, Yoko; Okada, Shinji; Matsumoto, Ichiro; Isohama, Yoichiro; Abe, Keiko; Miyata, Takeshi; Mishima, Satoshi

2006-10-01

309

Atmospheric sulphuric acid and aerosol formation: implications from atmospheric measurements for nucleation and early growth mechanisms  

Microsoft Academic Search

We have investigated the formation and early growth of atmospheric secondary aerosol particles building on atmospheric measurements. The measurements were part of the QUEST 2 campaign which took place in spring 2003 in Hyytiälä (Finland). During the campaign numerous new aerosol particle formation events occurred of which 15 were accompanied by gaseous sulphuric acid measurements. Our detailed analysis of these

S.-L. Sihto; M. Kulmala; V.-M. Kerminen; M. Dal Maso; T. Petäjä; I. Riipinen; H. Korhonen; F. Arnold; R. Janson; M. Boy; A. Laaksonen; K. E. J. Lehtinen

2006-01-01

310

Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study  

SciTech Connect

Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score {<=}1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

Cai Ling [Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, VD (Switzerland); Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Stauder, Michael C. [Mayo Clinic, Rochester, MN (United States); Zhang Yujing [Sun Yat-sen University Cancer Center, Guangzhou, Guangdong (China); Poortmans, Philip [Verbeeten Institute, Tilburg (Netherlands); Li Yexiong [Cancer Hospital, Chinese Academy of Medical Sciences, Beijing (China); Constantinou, Nicolaos [Theagenio Cancer Hospital, Thessaloniki, Macedonia (Greece); Thariat, Juliette [Centre Anti-Cancereux Antoine-Lacassagne, Nice, Cote d'Azur (France); Kadish, Sidney P. [University of Massachusetts Medical School, Worcester, MA (United States); Nguyen, Tan Dat [Institut Jean-Godinot, Reims, Champagne-Ardenne (France); Kirova, Youlia M. [Institut Curie, Paris (France); Ghadjar, Pirus [Inselspital, Bern University Hospital, and University of Bern (Switzerland); Weber, Damien C. [Hopitaux Universitaires de Geneve (Switzerland); Bertran, Victoria Tuset [Hospital Universitari Germans Trias i Pujol, Barcelona (Spain); Ozsahin, Mahmut [Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, VD (Switzerland); Mirimanoff, Rene-Olivier, E-mail: Rene-Olivier.Mirimanoff@chuv.ch [Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, VD (Switzerland)

2012-05-01

311

An automatic early stage alveolar-bone-resorption evaluation method on digital dental panoramic radiographs  

NASA Astrophysics Data System (ADS)

Periodontal disease is a kind of typical dental diseases, which affects many adults. The presence of alveolar bone resorption, which can be observed from dental panoramic radiographs, is one of the most important signs of the progression of periodontal disease. Automatically evaluating alveolar-bone resorption is of important clinic meaning in dental radiology. The purpose of this study was to propose a novel system for automated alveolar-bone-resorption evaluation from digital dental panoramic radiographs for the first time. The proposed system enables visualization and quantitative evaluation of alveolar bone resorption degree surrounding the teeth. It has the following procedures: (1) pre-processing for a test image; (2) detection of tooth root apices with Gabor filter and curve fitting for the root apex line; (3) detection of features related with alveolar bone by using image phase congruency map and template matching and curving fitting for the alveolar line; (4) detection of occlusion line with selected Gabor filter; (5) finally, evaluation of the quantitative alveolar-bone-resorption degree in the area surrounding teeth by simply computing the average ratio of the height of the alveolar bone and the height of the teeth. The proposed scheme was applied to 30 patient cases of digital panoramic radiographs, with alveolar bone resorption of different stages. Our initial trial on these test cases indicates that the quantitative evaluation results are correlated with the alveolar-boneresorption degree, although the performance still needs further improvement. Therefore it has potential clinical practicability.

Zhang, Min; Katsumata, Akitoshi; Muramatsu, Chisako; Hara, Takeshi; Suzuki, Hiroki; Fujita, Hiroshi

2014-03-01

312

Early magma ocean and core formation on Vesta  

NASA Astrophysics Data System (ADS)

The Dawn mission confirms predictions that the asteroid 4 Vesta is differentiated in an iron rich core, a silicate mantle and a basaltic crust, supports its identification as the parent body of the HEDs and provides revised values of e.g. the mass, the bulk density and the dimensions of the asteroid 4 Vesta. Although no distinct volcanic regions have been identified, resurfacing by igneous processes distinguishes Vesta from asteroids like Ceres with its primitive surface, or Lutetia, which retained its primordial surface composition (and may still be partially differentiated[1]). Vesta's core radius is estimated to be 107-113 km[2] (derived from the mass concentration towards the centre). We performed numerical calculations of the thermo-chemical evolution of Vesta adopting the new data obtained by the Dawn mission (mass, bulk density, radius). We have expanded the thermo-chemical evolution model of [3], which includes accretion, compaction, melting, associated changes of the material properties, advective heat transport and differentiation by porous flow, by considering convection and thus effective cooling in a magma ocean to analyse its formation and evolution on Vesta. For melt fractions below the rheologically critical melt fraction (RCMF) of ?50% the heat transport by melt segregation is modeled assuming melt flow in porous media and by supplementing the energy balance equation with additional advection terms. Above the RCMF the effective thermal conductivity keff is computed from the convective heat flux in the soft turbulence regime[4]. The parameter keff mimics the vigorous convection and heat flux of the magma ocean with a low viscosity. It amounts to O(106) W m-1K-1 and substitutes the thermal conductivity in the energy balance equation. We consider both instantaneous and continuous accretion (assuming late runaway material accumulation). In particular, we compare the evolution scenarios arising from the instantaneous accretion of Vesta at different formation times t0 (relative to the formation of the CAIs) with those for which the accretion durations ta is between 0.5 and 2.0 Ma. According to our results core formation is possible for formation times of up to 2.5 Ma after the CAIs. An important process for the formation and evolution of a magma ocean is the partitioning of 26Al and its relocation with the silicate melt. Previous models[5] suggest the formation of an internal magma ocean throughout the whole mantle beneath a solid crust. Thereby, the partitioning of 26Al is neglected. In contrast to that, if partitioning of 26Al into the melt is considered we obtain an about 1 km thick superficial magma ocean due to the enrichment of the radioactive nuclides in the liquid phase and redistribution towards the surface with the rising melt (for t0

Neumann, Wladimir; Breuer, Doris; Spohn, Tilman

2013-04-01

313

Cell sheet transplantation of cultured mesenchymal stem cells enhances bone formation in a rat nonunion model  

Microsoft Academic Search

Orthopedic surgeons have long been troubled by cases involving nonunion of fractured bones. This study aimed to enhance bone union by cell sheet transplantation of mesenchymal stem cells. A nonunion model was made in rat femur, and rat bone marrow cells were cultured in medium containing dexamethasone and ascorbic acid phosphate to create a cell sheet that could be scraped

Akifumi Nakamura; Manabu Akahane; Hideki Shigematsu; Mika Tadokoro; Yusuke Morita; Hajime Ohgushi; Yoshiko Dohi; Tomoaki Imamura; Yasuhito Tanaka

2010-01-01

314

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

PubMed Central

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

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

2006-01-01

315

Early Oligocene initiation of North Atlantic Deep Water formation  

NASA Astrophysics Data System (ADS)

Dating the onset of deep-water flow between the Arctic and North Atlantic oceans is critical for modelling climate change in the Northern Hemisphere and for explaining changes in global ocean circulation throughout the Cenozoic era (from about 65 million years ago to the present). In the early Cenozoic era, exchange between these two ocean basins was inhibited by the Greenland-Scotland ridge, but a gateway through the Faeroe-Shetland basin has been hypothesized. Previous estimates of the date marking the onset of deep-water circulation through this basin-on the basis of circumstantial evidence from neighbouring basins-have been contradictory, ranging from about 35 to 15 million years ago. Here we describe the newly discovered Southeast Faeroes drift, which extends for 120km parallel to the basin axis. The onset of deposition in this drift has been dated to the early Oligocene epoch (~35 million years ago) from a petroleum exploration borehole. We show that the drift was deposited under a southerly flow regime, and conclude that the initiation of deep-water circulation from the Norwegian Sea into the North Atlantic Ocean took place much earlier than is currently assumed in most numerical models of ancient ocean circulation.

Davies, Richard; Cartwright, Joseph; Pike, Jennifer; Line, Charles

2001-04-01

316

Early Oligocene initiation of North Atlantic Deep Water formation.  

PubMed

Dating the onset of deep-water flow between the Arctic and North Atlantic oceans is critical for modelling climate change in the Northern Hemisphere and for explaining changes in global ocean circulation throughout the Cenozoic era (from about 65 million years ago to the present). In the early Cenozoic era, exchange between these two ocean basins was inhibited by the Greenland-Scotland ridge, but a gateway through the Faeroe-Shetland basin has been hypothesized. Previous estimates of the date marking the onset of deep-water circulation through this basin-on the basis of circumstantial evidence from neighbouring basins-have been contradictory, ranging from about 35 to 15 million years ago. Here we describe the newly discovered Southeast Faeroes drift, which extends for 120 km parallel to the basin axis. The onset of deposition in this drift has been dated to the early Oligocene epoch ( approximately 35 million years ago) from a petroleum exploration borehole. We show that the drift was deposited under a southerly flow regime, and conclude that the initiation of deep-water circulation from the Norwegian Sea into the North Atlantic Ocean took place much earlier than is currently assumed in most numerical models of ancient ocean circulation. PMID:11309613

Davies, R; Cartwright, J; Pike, J; Line, C

2001-04-19

317

Natural variation in the extent of phosphorylation of bone phosphoproteins as a function of in vivo new bone formation induced by demineralized bone matrix in soft tissue and bony environments.  

PubMed Central

Implants of allogenic demineralized bone matrix were placed in distinct in vivo environments, i.e. calvarial (bony) and subcutaneous (soft tissue) sites. Detailed analyses of the biochemical components were performed. Quantitative levels of osteopontin (OPN), bone sialoprotein (BSP) and calcium phosphate (Ca-P) deposition within each implant environment varied as a function of new bone formation, and were substantially different in samples from calvarial and subcutaneous sites. Quantification of the extent of phosphorylation of affinity-purified OPN and BSP from such implants indicated that: (i) the number of mols of phosphoserine (P-Ser)/mol of affinity-purified OPN or BSP varied as a function of implant time and bone formation within both implant sites, and (ii) the 'effective P-Ser concentration' provided by the total OPN and BSP within each implant site varied and increased as a function of time, being approx. 5-fold higher for BSP in calvarial compared with subcutaneous implants. Peak levels of mols of P-Ser/mol of BSP coincided with maximum rates of Ca-P deposition in calvarial implants. Levels of OPN phosphorylation from both calvarial and subcutaneous implants also indicated fluctuations as a function of bone formation. Hence the present study, for the first time, provides direct evidence of natural variation in the extent of phosphorylation of both OPN and BSP as a function of time of mineralized tissue formation. Further evaluation of the data provides the first evidence of a direct and linear relationship between the rate of Ca-P deposition and the ratio of P-Ser-BSP/P-Ser-OPN for calvarial implants. Data for subcutaneous implants failed to provide such correlation. Overall, the present work demonstrates that the natural biological progression of the process of biomineralization follows strict criteria consistent with the anatomical location. Biomineralization fails to proceed in the same way in a soft tissue environment. PMID:12023890

Salih, Erdjan; Wang, Jinxi; Mah, James; Fluckiger, Rudolf

2002-01-01

318

Phenytoin and fluoride act in concert to stimulate bone formation and to increase bone volume in adult male rats  

Microsoft Academic Search

We have recently demonstrated that phenytoin is an osteogenic agent at low doses. The present paper describes observations that a mitogenic dose (i.e., 20 µM in BGJb medium) of fluoride significantly augments the phenytoin-dependent stimulation of normal human bone cell proliferation and alkaline phosphatase (ALP) activity in cell culture. Additionally, the present study was designed to investigate whether fluoride and

T. Ohta; J. E. Wergedal; T. Matsuyama; D. J. Baylink; K.-H. Wiliam Lau

1995-01-01

319

Effective immobilization of BMP-2 mediated by polydopamine coating on biodegradable nanofibers for enhanced in vivo bone formation.  

PubMed

Although bone morphogenic proteins (BMPs) have been widely used for bone regeneration, the ideal delivery system with optimized dose and minimized side effects is still active area of research. In this study, we developed bone morphogenetic protein-2(BMP-2) immobilized poly(l-lactide) (PLLA) nanofibers inspired by polydopamine, which could be ultimately used as membranes for guided bone regeneration, and investigated their effect on guidance of in vitro cell behavior and in vivo bone formation. Surface chemical analysis of the nanofibers confirmed successful immobilization of BMP-2 mediated by polydopamine, and about 90% of BMP-2 was stably retained on the nanofiber surface for at least 28 days. The alkaline phosphatase activity and calcium mineralization of human mesenchymal stem cells (hMSCs) after 14 days of in vitro culture was significantly enhanced on nanofibers immobilized with BMP-2. More importantly, BMP-2 at a relatively small dose was highly active following implantation to the critical-sized defect in the cranium of mice; radiographic analysis demonstrated that 77.8 ± 11.7% of newly formed bone was filled within the defect for a BMP-2-immobilized groups at the concentration of 124 ± 9 ng/cm(2), as compared to 5.9 ± 1.0 and 34.1 ± 5.5% recovery, for a defect-only and a polydopamine-only group, respectively. Scanning and transmission electron microscopy of samples from the BMP-2 immobilized group showed fibroblasts and osteoblasts with nanofiber strands in the middle of regenerated bone tissue, revealing the importance of interaction between implanted nanofibers and the neighboring extracellular environment. Taken together, our data support that the presentation of BMP-2 on the surface of nanofibers as immobilized by utilizing polydopamine chemistry may be an effective method to direct bone growth at relatively low local concentration. PMID:24942379

Cho, Hyeong-jin; Perikamana, Sajeesh Kumar Madhurakkat; Lee, Ji-hye; Lee, Jinkyu; Lee, Kyung-Mi; Shin, Choongsoo S; Shin, Heungsoo

2014-07-23

320

Nanohydroxyapatite shape and its potential role in bone formation: an analytical study.  

PubMed

Bone cells (osteoblasts) produce a collagen-rich matrix called osteoid, which is mineralized extracellularly by nanosized calcium phosphate (CaP). Synthetically produced CaP nanoparticles (NPs) have great potential for clinical application. However few studies have compared the effect of CaP NPs with different properties, such as shape and aspect ratio, on the survival and behaviour of active bone-producing cells, such as primary human osteoblasts (HOBs). This study aimed to investigate the biocompatibility and ultrastructural effects of two differently shaped hydroxyapatite [Ca10(PO4)6(OH)2] nanoparticles (HA NPs), round- (aspect ratio 2.12, AR2) and rice-shaped (aspect ratio 3.79, AR4). The ultrastructural response and initial extracellular matrix (ECM) formation of HOBs to HA NPs were observed, as well as matrix vesicle release. A transmission electron microscopy (TEM)-based X-ray microanalytical technique was used to measure cytoplasmic ion levels, including calcium (Ca), phosphorus (P), sodium (Na) and potassium (K). K/Na ratios were used as a measure of cell viability. Following HA NP stimulation, all measured cytoplasmic ion levels increased. AR2 NPs had a greater osteogenic effect on osteoblasts compared with AR4 NPs, including alkaline phosphatase activity and matrix vesicle release. However, they produced only a moderate increase in intracellular Ca and P levels compared with AR4. This suggests that particular Ca and P concentrations may be required for, or indicative of, optimal osteoblast activity. Cell viability, as measured by Na and K microanalysis, was best maintained in AR2. Initial formation of osteoblast ECM was altered in the presence of either HA NP, and immuno-TEM identified fibronectin and matrilin-3 as two ECM proteins affected. Matrilin-3 is here described for the first time as being expressed by cultured osteoblasts. In summary, this novel and in-depth study has demonstrated that HA NP shape can influence a range of different parameters related to osteoblast viability and activity. PMID:24478288

Kalia, Priya; Vizcay-Barrena, Gema; Fan, Jian Ping; Warley, Alice; Di Silvio, Lucy; Huang, Jie

2014-04-01

321

Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches  

PubMed Central

Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315.BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315.BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient ?dblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma. PMID:25272036

Wong, David; Winter, Oliver; Hartig, Christina; Siebels, Svenja; Szyska, Martin; Tiburzy, Benjamin; Meng, Lingzhang; Kulkarni, Upasana; Fahnrich, Anke; Bommert, Kurt; Bargou, Ralf; Berek, Claudia; Chu, Van Trung; Bogen, Bjarne; Jundt, Franziska; Manz, Rudolf Armin

2014-01-01

322

Fossil Microorganisms and Formation of Early Precambrian Weathering Profiles  

NASA Technical Reports Server (NTRS)

Weathering crusts are the only reliable evidences of the existence of continental conditions. Often they are the only source of information about exogenous processes and subsequently about conditions under which the development of the biosphere occurred. A complex of diverse fossil microorganisms was discovered as a result of Scanning Electron Microscope investigations. The chemical composition of the discovered fossils is identical to that of the host rocks and is represented by Si, Al, Fe, Ca and Mg. Probably, the microorganisms fixed in rocks played the role of catalyst. The decomposition of minerals comprising the rocks and their transformation into clayey (argillaceous) minerals, most likely occurred under the influence of microorganisms. And may be unique weathering crusts of Early Precambrian were formed due to interaction between specific composition of microorganism assemblage and conditions of hypergene transformations. So it is possible to speak about colonization of land by microbes already at that time and about existence of single raw from weathering crusts (Primitive soils) to real soils.

Rozanov, A. Yu; Astafieva, M. M.; Vrevsky, A. B.; Alfimova, N. A.; Matrenichev, V. A.; Hoover, R. B.

2009-01-01

323

Early Stage Primary Bone Lymphoma: a retrospective, multicenter Rare Cancer Network (RCN) study  

Microsoft Academic Search

PurposePrimary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with stage I and II PBL.

Ling Cai; Michael C. Stauder; Yu-Jing Zhang; Philip Poortmans; Ye-Xiong Li; Nicolaos Constantinou; Juliette Thariat; Sidney P. Kadish; Tan Dat Nguyen; Youlia M. Kirova; Pirus Ghadjar; Damien C. Weber; Victoria Tuset Bertran; Mahmut Ozsahin; René-Olivier Mirimanoff

324

Temporomandibular Joint Bone Tissue Resorption in Patients with Early Rheumatoid Arthritis Can Be Predicted by Joint Crepitus and Plasma Glutamate Level  

PubMed Central

The aim was to investigate whether bone tissue resorption in early RA is related to crepitus of the temporomandibular joint (TMJ) and systemic levels of inflammatory mediators and markers and sex steroid hormones. Twentynine women and 18 men with recently diagnosed RA were examined for TMJ bone erosions with computerized tomography and TMJ crepitus was assessed. Blood samples were analyzed for glutamate, 5-HT, TNF, IL-1?, IL-6, VEGF, inflammatory markers, and estradiol, progesterone and testosterone. The TMJ erosion score was positively correlated to glutamate, and TMJ crepitus where crepitus, glutamate and ESR explained 40% of the variation in the bone erosion score. In the patients without crepitus, bone erosion score was positively correlated to glutamate, which was not the case in the patients with crepitus. In conclusion, the results of this study show that TMJ bone tissue resorption can be predicted by TMJ crepitus and glutamate in early RA. PMID:20671920

Hajati, Anna-Kari; Nasstrom, Karin; Alstergren, Per; Bratt, Johan; Kopp, Sigvard

2010-01-01

325

A model for core formation in the early Earth  

NASA Technical Reports Server (NTRS)

Two basic types exogenous models were proposed to account for siderophile and chalcophile element abundances in the Earth's upper mantle. The first model requires that the Earth be depleted in volatiles and that, after a core formation event which extracted the most siderophile elements into the core, additional noble siderophile elements (Pt, Ir, Au) were added as a late veneer and mixed into the mantle. The second model postulates a reduced Earth with approximately CI elemental abundances in which a primary core forming event depleted all siderophile elements in the mantle. The plausibility of models which require fine scale mixing of chondritic material into the upper mantle is analyzed. Mixing in liquids is more efficient, but large degrees of silicate partial melting will facilitate the separation of magma from residual solids. Any external events affecting the upper mantle of the Earth should also be evident in the Moon; but siderophile and chalcophile element abundance patterns inferred for the mantles of the Earth and Moon differ. There appear to be significant physical difficulties associated with chondritic veneer models.

Jones, J. H.; Drake, M. J.

1985-01-01

326

Treatment of an aneurysmal bone cyst of the second metatarsal using an endoscopic approach.  

PubMed

An aneurysmal bone cyst is a benign solitary lesion of unknown etiology. A case report is presented of recurrence of an aneurysmal bone cyst in the foot that was treated with endoscopic curettage without bone grafting. Bone remodeling and bone formation were completed in the early stages postsurgically. At 2-year follow-up, the patient is asymptomatic with no radiographic evidence of recurrence. PMID:12194514

Otsuka, Takanobu; Kobayashi, Masaaki; Sekiya, Isato; Yonezawa, Masato; Kamiyama, Fumiaki; Matsushita, Yasusi; Ootani, Masafumi; Matsui, Nobuo

2002-01-01

327

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

PubMed Central

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.

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

2014-01-01

328

Evaluation of early cellular influences of bone morphogenetic proteins 12 and 2 on equine superficial digital flexor tenocytes and bone marrow–derived mesenchymal stem cells in vitro  

PubMed Central

Objective To evaluate early cellular influences of bone morphogenetic protein (BMP)12 and BMP2 on equine superficial digital flexor tenocytes (SDFTNs) and equine bone marrow–derived mesenchymal stem cells (BMDMSCs). Animals 9 adult clinically normal horses. Procedures BMDMSCs and SDFTNs were cultured in monolayer, either untreated or transduced with adenovirus encoding green fluorescent protein, adenovirus encoding BMP12, or adenovirus encoding BMP2. Cytomorphologic, cytochemical, immunocytochemical, and reverse transcriptase–quantitative PCR (RT-qPCR) analyses were performed on days 3 and 6. Genetic profiling for effects of BMP12 was evaluated by use of an equine gene expression microarray on day 6. Results BMDMSCs and SDFTNs had high BMP12 gene expression and remained viable and healthy for at least 6 days. Type l collagen immunocytochemical staining for SDFTNs and tenocyte-like morphology for SDFTNs and BMDMSCs were greatest in BMP12 cells. Cartilage oligomeric matrix protein, as determined via RT-qPCR assay, and chondroitin sulfate, as determined via gene expression microarray analysis, were upregulated relative to control groups in SDFTN-BMP12 cells. The BMDMSCs and SDFTNs became mineralized with BMP2, but not BMP12. Superficial digital flexor tenocytes responded to BMP12 with upregulation of genes relevant to tendon healing and without mineralization as seen with BMP2. Conclusions and Clinical Relevance Targeted equine SDFTNs may respond to BMP12 with improved tenocyte morphology and without mineralization, as seen with BMP2. Bone marrow–derived mesenchymal stem cells may be able to serve as a cell delivery method for BMP12. PMID:20043789

Murray, Shannon J.; Santangelo, Kelly S.; Bertone, Alicia L.

2014-01-01

329

The effect of rhBMP-2 and PRP delivery by biodegradable ?-tricalcium phosphate scaffolds on new bone formation in a non-through rabbit cranial defect model  

PubMed Central

This study evaluated whether the combination of biodegradable ?-tricalcium phosphate (?-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. ?-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated ?-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated ?-TCP scaffolds (p<0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation. PMID:23779152

Lim, Hyun-Pil; Mercado-Pagan, Angel E.; Yun, Kwi-Dug; Kang, Seong-Soo; Choi, Taek-Hue; Bishop, Julius; Koh, Jeong-Tae; Maloney, William; Lee, Kwang-Min; Yang, Yunzhi; Park, Sang-Won

2013-01-01

330

Characterization of new bone formation in gout: a quantitative site-by-site analysis using plain radiography and computed tomography  

PubMed Central

Introduction Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and tophus. Methods Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed. Results The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous tophus were more likely to have NBF; if tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001. Conclusions This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, tophus, and formation of new bone during the process of joint remodelling in gout. PMID:22794662

2012-01-01

331

Bone remodelling in osteoporosis  

Microsoft Academic Search

Summary Bone remodelling, a highly regulated succession of events, is the temporal sequence of osteoclastic bone resorption and osteoblastic bone formation. Bone loss with age and in osteoporotic patients is due to a desequilibrium between both processus. Bone histomorphometry was the method used to measure these events. Its shows clearly that, with age, the quantity of bone formed in one

M. C. de VERNEJOUL

1989-01-01

332

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone  

PubMed Central

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

2012-01-01

333

A correlation analysis between bone formation rate and bioelectric potentials in rabbit tibia  

Microsoft Academic Search

Summary  The origin of the bioelectric potentials in unstressed living bones is still an open question. Blood-flow in vessels, stationary\\u000a potentials on peripheral nerves, muscle injury potentials, and viability of bone cells are claimed to be possible sites of\\u000a origin of the electric potentials recorded on bone surface.\\u000a \\u000a The present data show that the topographic quantitative distribution of tetracycline labeling at

A. Rubinacci; L. Tessari

1983-01-01

334

Divergent Resorbability and Effects on Osteoclast Formation of Commonly Used Bone Substitutes in a Human In Vitro-Assay  

PubMed Central

Bioactive bone substitute materials are a valuable alternative to autologous bone transplantations in the repair of skeletal defects. However, clinical studies have reported varying success rates for many commonly used biomaterials. While osteoblasts have traditionally been regarded as key players mediating osseointegration, increasing evidence suggests that bone-resorbing osteoclasts are of crucial importance for the longevity of applied biomaterials. As no standardized data on the resorbability of biomaterials exists, we applied an in vitro-assay to compare ten commonly used bone substitutes. Human peripheral blood mononuclear cells (PBMCs) were differentiated into osteoclasts in the co-presence of dentin chips and biomaterials or dentin alone (control) for a period of 28 days. Osteoclast maturation was monitored on day 0 and 14 by light microscopy, and material-dependent changes in extracellular pH were assessed twice weekly. Mature osteoclasts were quantified using TRAP stainings on day 28 and their resorptive activity was determined on dentin (toluidin blue staining) and biomaterials (scanning electron microscopy, SEM). The analyzed biomaterials caused specific changes in the pH, which were correlated with osteoclast multinuclearity (r?=?0.942; p?=?0.034) and activity on biomaterials (r?=?0.594; p?=?0.041). Perossal led to a significant reduction of pH, nuclei per osteoclast and dentin resorption, whereas Tutogen bovine and Tutobone human strikingly increased all three parameters. Furthermore, natural biomaterials were resorbed more rapidly than synthetic biomaterials leading to differential relative resorption coefficients, which indicate whether bone substitutes lead to a balanced resorption or preferential resorption of either the biomaterial or the surrounding bone. Taken together, this study for the first time compares the effects of widely used biomaterials on osteoclast formation and resorbability in an unbiased approach that may now aid in improving the preclinical evaluation of bone substitute materials. PMID:23071629

Busse, Bjorn; Schilling, Arndt F.; Schinke, Thorsten; Amling, Michael; Lange, Tobias

2012-01-01

335

Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production  

PubMed Central

The L-gulono-?-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels. PMID:24386598

Kim, Won; Bae, Seyeon; Kim, Hyemin; Kim, Yejin; Choi, Jiwon; Lim, Sun Young; Lee, Hei Jin; Lee, Jihyuk; Choi, Jiyea; Jang, Mirim; Lee, Kyoung Eun; Chung, Sun G.; Hwang, Young-il

2013-01-01

336

High Calcium Bioglass Enhances Differentiation and Survival of Endothelial Progenitor Cells, Inducing Early Vascularization in Critical Size Bone Defects  

PubMed Central

Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC), seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA) and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with ?-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n?=?12). Controls (n?=?6) received BG40 and the treatment group (n?=?6) received BG40 seeded with 5×105 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects. PMID:24244419

Nguyen Ngoc, Christina; Meier, Simon; Nau, Christoph; Schaible, Alexander; Marzi, Ingo; Henrich, Dirk

2013-01-01

337

The Epochs of Early-Type Galaxy Formation as a Function of Environment  

Microsoft Academic Search

The aim of this paper is to set constraints on the epochs of early-type galaxy formation through the ``archaeology'' of the stellar populations in local galaxies. Using our models of absorption-line indices that account for variable abundance ratios, we derive ages, total metallicities, and element ratios of 124 early-type galaxies in high- and low-density environments. The data are analyzed by

Daniel Thomas; Claudia Maraston; Ralf Bender; Claudia Mendes de Oliveira

2005-01-01

338

Dynamics of Alloplastic Bone Grafts on an Early Stage of Corticotomy-Facilitated Orthodontic Tooth Movement in Beagle Dogs  

PubMed Central

Alveolar augmented corticotomy is effective in accelerating orthodontic tooth movement, but the effect only lasts for a relatively short time. Therefore, the purpose of this study was to investigate the underlying biology of the immediate periodontal response to orthodontic tooth movement after a corticotomy with alloplastic bone grafts. The results demonstrated that measurable tooth movement began as early as 3 days after the intervention in beagle dogs. Based on the results and histological findings, augmented corticotomy-facilitated orthodontic tooth movement might enhance the condition of the periodontal tissue and the stability of the outcomes of orthodontic treatment.

Choi, Hyung-Joo; Kim, Tae-Woo

2014-01-01

339

The formation of early stage adipocere in submerged remains: a preliminary experimental study.  

PubMed

In some circumstances, the presence of adipocere may retard decomposition and complicate postmortem interval estimation. This article explores the correlation between Accumulated Degree Days (ADD) and early stage formation of adipocere. Sixty wild rabbit (Oryctolagus cuniculus) carcasses were used in this experiment; a control group (N = 30) deposited directly on the ground surface and an experimental group (N = 30) completely submersed in water in individual buckets. Data (water and inner body temperature, pH, and total body score) were collected every 100 ADD. Results indicated that early stage adipocere is correlated to ADD and that its formation on submersed remains is more likely to occur after 630 ADD. Skin sloughing promoted the formation of adipocere. No adipocere was formed on any of the control group rabbits. This study also highlights the fact that multiple factors influence adipocere formation and it is suggested that further research needs to be conducted into this area. PMID:22150268

Widya, Marcella; Moffatt, Colin; Simmons, Tal

2012-03-01

340

Bone-like apatite formation on HA\\/316L stainless steel composite surface in simulated body fluid  

Microsoft Academic Search

HA\\/316L stainless steel(316L SS) biocomposites were prepared by hot-pressing technique. The formation of bone-like apatite on the biocomposite surfaces in simulated body fluid(SBF) was analyzed by digital pH meter, plasma emission spectrometer, scanning electron microscope(SEM) and energy dispersive X-ray energy spectrometer(EDX). The results indicate that the pH value in SBF varies slightly during the immersion. It is a dynamic process

Xin FAN; Jian CHEN; Jian-peng ZOU; Qian WAN; Zhong-cheng ZHOU; Jian-ming RUAN

2009-01-01

341

The effect of devitalized trabecular bone on the formation of osteochondral tissue-engineered constructs  

PubMed Central

In the current study, evidence is presented demonstrating that devitalized trabecular bone has an inhibitory effect on in vitro chondral tissue development when used as a base material for the tissue-engineering of osteochondral constructs for cartilage repair. Chondrocyte-seeded agarose hydrogel constructs were cultured alone or attached to an underlying bony base in a chemically defined medium formulation that has been shown to yield engineered cartilaginous tissue with native Young's modulus (EY) and glycosaminoglycan (GAG) content. By day 42 in culture the incorporation of a bony base significantly reduced these properties (EY = 87 ± 12 kPa, GAG = 1.9 ± 0.8%ww) compared to the gel-alone group (EY = 642 ± 97 kPa, GAG = 4.6 ± 1.4%ww). Similarly, the mechanical and biochemical properties of chondrocyte-seeded agarose constructs were inhibited when co-cultured adjacent to bone (unattached), suggesting that soluble factors rather than direct cell–bone interactions mediate the chondro-inhibitory bone effects. Altering the method of bone preparation, including demineralization, or the timing of bone introduction in co-culture did not ameliorate the effects. In contrast, osteochondral constructs with native cartilage properties (EY = 730 ± 65 kPa, GAG = 5.2 ± 0.9%ww) were achieved when a porous tantalum metal base material was adopted instead of bone. This work suggests that devitalized bone may not be a suitable substrate for long-term cultivation of osteochondral grafts. PMID:18718655

Lima, Eric G.; Chao, Pen-hsiu Grace; Ateshian, Gerard A.; Bal, B. Sonny; Cook, James L.; Vunjak-Novakovic, Gordana; Hung, Clark T.

2008-01-01

342

The Fos-related antigen Fra-1 is an activator of bone matrix formation  

PubMed Central

Ectopic expression of the transcription factor Fra-1 in transgenic mice leads to osteosclerosis, a bone disorder characterized by increased bone mass. The molecular basis for this phenotype is unknown and Fra-1 functions cannot be studied by a conventional loss-of-function approach, since fra-1-knockout mice die in utero likely due to placental defects. Here we show that the lethality of fra-1-knockout mice can be rescued by specific deletion of Fra-1 only in the mouse embryo and not in the placenta. Mice lacking Fra-1 (fra-1?/?) are viable and develop osteopenia, a low bone mass disease. Long bones of fra-1?/? mice appear to have normal osteoclasts but express reduced amounts of bone matrix components produced by osteoblasts and chondrocytes such as osteocalcin, collagen1a2 and matrix Gla protein. The gene for matrix Gla protein seems to be a specific target of Fra-1 since its expression was markedly increased in the long bones of fra-1-transgenic mice. These results uncover a novel function of Fra-1 in regulating bone mass through bone matrix production by osteoblasts and chondrocytes. PMID:15229648

Eferl, Robert; Hoebertz, Astrid; Schilling, Arndt F; Rath, Martina; Karreth, Florian; Kenner, Lukas; Amling, Michael; Wagner, Erwin F

2004-01-01

343

Castor oil polymer induces bone formation with high matrix metalloproteinase-2 expression.  

PubMed

The aim of this study was to evaluate the modulation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expression in newly formed bone tissue at the interface between implants derived from castor oil (Ricinus communis) polymer and the tibia medullary canal. Forty-four rabbits were assigned to either Group 1 (n?=?12; control) or Group 2 (n?=?30), which had the tibial medullary canals reamed bilaterally and filled with polymer. CT scans showed no space between the material surface and the bone at the implant/bone marrow interface, and the density of the tissues at this interface was similar to the density measured of other regions of the bone. At 90 days postimplantation, the interface with the polymer presented a thick layer of newly formed bone tissue rich in osteocytes. This tissue exhibited ongoing maturation at 120 and 150 days postimplantation. Overall, bone remodeling process was accompanied by positive modulation of MMP-2 and low MMP-9 expression. Differently, in control group, the internal surface close to the medullary canal was lined by osteoblasts, followed by a bone tissue zone with few lacunae filled with osteocytes. Maturation of the tissue of the medullary internal surface occurred in the inner region, with the bone being nonlamellar. PMID:23670892

Saran, Wallace Rocha; Chierice, Gilberto Orivaldo; da Silva, Raquel Assed Bezerra; de Queiroz, Alexandra Mussolino; Paula-Silva, Francisco Wanderley Garcia; da Silva, Léa Assed Bezerra

2014-02-01

344

The effect of early growth dynamics on determining particle formation rates of a nucleating burst  

NASA Astrophysics Data System (ADS)

We studied growth and coagulation in the early stages of a nucleating particle population using a numerical model that solves the for particle concentration on the highest possible size resolution. We found that commonly used methods for deriving particle formation rates from nanoparticle concentration measurements may not result in correct estimates for the formation rate. This influences reliability of the observed vapour concentration dependency of the nucleation rate, which is often used to draw conclusions of the nucleation mechanism.

Dal Maso, Miikka; Korhonen, H.; Lehtinen, Kari; Vehkamäki, H.

2013-05-01

345

The Formation History of Early-Type Galaxies: An Observational Perspective  

Microsoft Academic Search

This talk investigates the formation of early-type galaxies from a\\u000adeliberately observational view point. I begin by reviewing the conclusions\\u000athat can be reached by comparing the detailed properties of galaxies in\\u000apresent-day clusters, focusing on the colour-magnitude relation in particular.\\u000aThe overriding picture is one of homogeneity, implying a remarkable uniformity\\u000ain the formation of these galaxies. This picture

Richard G. Bower; Ale Terlevich; Tadayuki Kodama; Nelson Caldwell

1998-01-01

346

The Formation History of Early-Type Galaxies: an Observational Perspective  

Microsoft Academic Search

This talk investigates the formation of early-type galaxies from a deliberately observational view point. I begin by reviewing the conclusions that can be reached by comparing the detailed properties of galaxies in present-day clusters, focusing on the colour-magnitude relation in particular. The overriding picture is one of homogeneity, implying a remarkable uniformity in the formation of these galaxies. This picture

R. G. Bower; A. Terlevich; T. Kodama; N. Caldwell

1999-01-01

347

A New Piezoelectric Actuator Induces Bone Formation In Vivo: A Preliminary Study  

PubMed Central

This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth. PMID:22701304

Reis, Joana; Frias, Clara; Canto e Castro, Carlos; Botelho, Maria Luisa; Marques, Antonio Torres; Simoes, Jose Antonio Oliveira; Capela e Silva, Fernando; Potes, Jose

2012-01-01

348

Engineering endochondral bone: in vivo studies.  

PubMed

The use of biomaterials to replace lost bone has been a common practice for decades. More recently, the demands for bone repair and regeneration have pushed research into the use of cultured cells and growth factors in association with these materials. Here we report a novel approach to engineer new bone using a transient cartilage scaffold to induce endochondral ossification. Chondrocyte/chitosan scaffolds (both a transient cartilage scaffold-experimental-and a permanent cartilage scaffold-control) were prepared and implanted subcutaneously in nude mice. Bone formation was evaluated over a period of 5 months. Mineralization was assessed by Faxitron, micro computed tomography, backscatter electrons, and Fourier transform infrared spectroscopy analyses. Histological analysis provided further information on tissue changes in and around the implanted scaffolds. The deposition of ectopic bone was detected in the surface of the experimental implants as early as 1 month after implantation. After 3 months, bone trabeculae and bone marrow cavities were formed inside the scaffolds. The bone deposited was similar to the bone of the mice vertebra. Interestingly, no bone formation was observed in control implants. In conclusion, an engineered transient cartilage template carries all the signals necessary to induce endochondral bone formation in vivo. PMID:18759673

Oliveira, Serafim M; Mijares, Dindo Q; Turner, Gloria; Amaral, Isabel F; Barbosa, Mário A; Teixeira, Cristina C

2009-03-01

349

Engineering Endochondral Bone: In Vivo Studies  

PubMed Central

The use of biomaterials to replace lost bone has been a common practice for decades. More recently, the demands for bone repair and regeneration have pushed research into the use of cultured cells and growth factors in association with these materials. Here we report a novel approach to engineer new bone using a transient cartilage scaffold to induce endochondral ossification. Chondrocyte/chitosan scaffolds (both a transient cartilage scaffold—experimental—and a permanent cartilage scaffold—control) were prepared and implanted subcutaneously in nude mice. Bone formation was evaluated over a period of 5 months. Mineralization was assessed by Faxitron, micro computed tomography, backscatter electrons, and Fourier transform infrared spectroscopy analyses. Histological analysis provided further information on tissue changes in and around the implanted scaffolds. The deposition of ectopic bone was detected in the surface of the experimental implants as early as 1 month after implantation. After 3 months, bone trabeculae and bone marrow cavities were formed inside the scaffolds. The bone deposited was similar to the bone of the mice vertebra. Interestingly, no bone formation was observed in control implants. In conclusion, an engineered transient cartilage template carries all the signals necessary to induce endochondral bone formation in vivo. PMID:18759673

Oliveira, Serafim M.; Mijares, Dindo Q.; Turner, Gloria; Amaral, Isabel F.; Barbosa, Mário A.

2009-01-01

350

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)

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.

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

351

Isolation and Molecular Profiling of Bone Marrow Micrometastases Identifies TWIST1 as a Marker of Early Tumor Relapse in Breast Cancer Patients  

PubMed Central

Purpose Micrometastatic cells detected in the bone marrow have prognostic significance in breast cancer. These cells are heterogeneous and likely do not exhibit uniform biological behavior. To understand the molecular diversity of disseminated cancer cells that reside in bone marrow, we enriched this cell population and did global gene expression profiling in the context of a prospective clinical trial involving women with clinical stage II/III breast cancer undergoing neoadjuvant chemotherapy. Experimental Design Enrichment of TACSTD1 (EpCAM)-expressing cells from bone marrow of breast cancer patients was achieved using immunomagnetic beads. Gene expression profiles were compared between enriched cell populations and whole bone marrow from 5 normal volunteers and 23 breast cancer patients after neoadjuvant chemotherapy treatment. Enriched cells from bone marrow samples of breast cancer patients before treatment or at 1 year follow-up were also analyzed (total of 87 data sets). The expression of transcripts specifically detected in enriched cell populations from breast cancer patients was correlated with 1-year clinical outcome using quantitative reverse transcription-PCR in an independent cohort of bone marrow samples. Results Analysis of EpCAM-enriched bone marrow cells revealed specific expression of a sub-group of transcripts, including the metastasis regulator, TWIST1. Most transcripts identified, including TWIST1, were not expressed in enriched populations of bone marrow from normal volunteers, suggesting that this expression profile reflects a signature of breast cancer bone marrow micrometastases that persist after chemotherapy. In an independent set of bone marrow samples obtained before any treatment, TWIST1 expression correlated with early disease relapse. Conclusions Disseminated breast cancer cells present in bone marrow after chemotherapy possess unique transcriptional signatures. Genes whose expression is overrepresented in these cell populations, such as TWIST1, may prove to be excellent markers of early distant relapse in breast cancer patients. PMID:17785550

Watson, Mark A.; Ylagan, Lourdes R.; Trinkaus, Kathryn M.; Gillanders, William E.; Naughton, Michael J.; Weilbaecher, Katherine N.; Fleming, Timothy P.; Aft, Rebecca L.

2009-01-01

352

Comparison of effect of BMP2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma  

Microsoft Academic Search

The human adult stem cells from bone marrow stroma referred to as mesenchymal stem cells or marrow stromal cells (MSCs) are of interest because they are easily isolated and expanded and are capable of multipotential differentiation. Here, we examined the ability of recombinant human bone morphogenetic protein (BMP)-2, -4, and -6 to enhance in vitro cartilage formation of MSCs. Human

Ichiro Sekiya; Benjamin L. Larson; Jussi T. Vuoristo; Roxanne L. Reger; Darwin J. Prockop

2005-01-01

353

Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study  

Microsoft Academic Search

Objective: The effect of adalimumab on hand osteo- porosis was examined and related to radiographic joint damage in the three treatment arms of the PREMIER study: adalimumab plus methotrexate, adalimumab and methotrexate monotherapy. Predictors of hand bone loss were also searched for. Methods: 768 patients (537 fulfilled 2 years) with rheumatoid arthritis (RA) for less than 3 years, never treated

M Hoff; T K Kvien; J Kalvesten; A Elden; G Haugeberg

2009-01-01

354

IL-23 Is Critical for Induction of Arthritis, Osteoclast Formation, and Maintenance of Bone Mass  

PubMed Central

The role of IL-23 in the development of arthritis and bone metabolism was studied using systemic IL-23 exposure in adult mice via hydrodynamic delivery of IL-23 minicircle DNA in vivo and in mice genetically deficient in IL-23. Systemic IL-23 exposure induced chronic arthritis, severe bone loss, and myelopoiesis in the bone marrow and spleen, which resulted in increased osteoclast differentiation and systemic bone loss. The effect of IL-23 was partly dependent on CD4+ T cells, IL-17A, and TNF, but could not be reproduced by overexpression of IL-17A in vivo. A key role in the IL-23–induced arthritis was made by the expansion and activity of myeloid cells. Bone marrow macrophages derived from IL-23p19?/? mice showed a slower maturation into osteoclasts with reduced tartrate-resistant acid phosphatase-positive cells and dentine resorption capacity in in vitro osteoclastogenesis assays. This correlated with fewer multinucleated osteoclast-like cells and more trabecular bone volume and number in 26-wk-old male IL-23p19?/? mice compared with control animals. Collectively, our data suggest that systemic IL-23 exposure induces the expansion of a myeloid lineage osteoclast precursor, and targeting IL-23 pathway may combat inflammation-driven bone destruction as observed in rheumatoid arthritis and other autoimmune arthritides. The Journal of Immunology, 2011, 187: 951–959. PMID:21670317

Adamopoulos, Iannis E.; Tessmer, Marlowe; Chao, Cheng-Chi; Adda, Sarvesh; Gorman, Dan; Petro, Mary; Chou, Chuan-Chu; Pierce, Robert H.; Yao, Wei; Lane, Nancy E.; Laface, Drake; Bowman, Edward P.

2014-01-01

355

A new fossil porpoise (Cetacea; Delphinoidea; Phocoenidae) from the Early Pliocene Horokaoshirarika Formation, Hokkaido, Japan  

Microsoft Academic Search

A new fossil odontocete genus and species, Numataphocoena yamashitai is from the Early Pliocene Horokaoshirarika Formation, Numata, central Hokkaido, Japan. The porpoise was probably buried in relatively shallow marine sediments. This specimen consists of an incomplete skull, a right periotic and tympanic bulla, a posterior part of the right mandible, 23 isolated teeth, a nearly complete vertebral column, a chevron,

Hiroto Ichishima; Masaichi Kimura

2000-01-01

356

Parents' Marital Distress, Divorce, and Remarriage: Links with Daughters' Early Family Formation Transitions  

ERIC Educational Resources Information Center

The authors used data from the Add Health study to estimate the effects of parents' marital status and relationship distress on daughters' early family formation transitions. Outcomes included traditional transitions (marriage and marital births) and nontraditional transitions (cohabitation and nonmarital births). Relationship distress among…

Amato, Paul R.; Kane, Jennifer B.

2011-01-01

357

Early Pubertal Timing and the Union Formation Behaviors of Young Women  

Microsoft Academic Search

This study examined whether the transition into adolescence, proxied by pubertal timing, shaped the transition into adulthood, proxied by union formation behaviors, among contemporary American women. In a sample drawn from Add Health (n = 7,523), early maturing girls reported an accelerated transition to marriage and cohabitation in young adulthood, net of family structure history, academic achievement in high school,

Shannon E. Cavanagh

2011-01-01

358

Early Visean bryozoans from the Shishtu II Member, Shishtu Formation, central Iran  

NASA Astrophysics Data System (ADS)

Four bryozoan species are described from the upper member (Shishtu II) (Visean, Early Carboniferous=Mississippian) of the Shishtu Formation of central Iran: Nikiforovella ulbensis Nekhoroshev, 1956, Nicklesopora elegantulaformis (Nekhoroshev, 1956), Primorella cf. iranica Gorjunova, 2006, and Nikiforopora intermedia (Nikiforova, 1950). This Visean assemblage shows close palaeogeographical affinities of Iran with Kazakhstan and Russia (eastern Transbaikalia, Kurgan region).

Tolokonnikova, Zoya; Yazdi-Moghadam, Mohsen

2013-12-01

359

Accelerated in vitro fibril formation by a mutant ?-synuclein linked to early-onset Parkinson disease  

Microsoft Academic Search

Two mutations in the gene encoding ?-synuclein have been linked to early-onset Parkinson's disease (PD). ?-Synuclein is a component of Lewy bodies, the fibrous cytoplasmic inclusions characteristic of nigral dopaminergic neurons in the PD brain. This connection between genetics and pathology suggests that the ?-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation. To test this, we studied

Kelly A. Conway; James D. Harper; Peter T. Lansbury

1998-01-01

360

Calsoyasuchus valliceps, a new crocodyliform from the Early Jurassic Kayenta Formation of Arizona  

Microsoft Academic Search

We describe a new fossil crocodyliform archosaur from the Early Jurassic Kayenta Formation of the Navajo Nation that is surprisingly derived for so ancient a specimen. High-resolution X-ray CT analysis reveals that its long snout houses an extensive system of pneumatic paranasal cavities. These are among the most distinctive features of modern crocodylians, yet the evolutionary history of this unique

Ronald S. Tykoski; Timothy B. Rowe; Richard A. Ketcham; Matthew W. Colbert

2002-01-01

361

CO2-SO2 clathrate hydrate formation on early Mars1 Eric Chassefirea,b  

E-print Network

atmosphere was necessary in order to keep28 early Mars warm and wet. However, current models have not been a significant formation of sulfate37 minerals during the Noachian and inhibiting carbonates from forming of episodic warm47 episodes facilitated by the release of SO2 to the atmosphere. These episodes could explain

Boyer, Edmond

362

Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease  

Microsoft Academic Search

Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the

A. C. Leskovjan; L. Miller; A. Kretlow; A. Lanzirotti; R. Barrea; S. Vogt

2010-01-01

363

Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease  

Microsoft Academic Search

Elevated brain iron content, which has been observed in late-stage human Alzheimer's disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the

Andreana C. Leskovjan; Ariane Kretlow; Antonio Lanzirotti; Raul Barrea; Stefan Vogt; Lisa M. Miller

2011-01-01