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1

A plant virus substrate induces early upregulation of BMP2 for rapid bone formation.  

PubMed

Many nanoscale materials have been developed to investigate the effects on stem cell differentiations via topographical and chemical cues for applications in tissue engineering and regenerative medicine. The use of plant viruses as cell supporting substrates has been of particular interest due to the rapid induction of bone marrow derived mesenchymal stem cells (BMSCs) towards osteogenic cells. In this study, the role of Tobacco mosaic virus (TMV) and its early effects on osteoinduction with particular emphasis on the regulation of bone morphogenetic protein-2 (BMP2) was examined. We observed that the cells on the virus substrate immediately aggregated and formed bone-like nodules within 24 hours. An immediate increase in BMP2 gene and protein expression for cells on the TMV substrate was observed within 8 hours of osteoinduction. Moreover, BMP2 expression was highly localized to cells within the cell aggregates. This enhanced differentiation only occurred when TMV was coated on a solid support but not upon adding the virus to the media solution. Taken together, the results from this study highlight the potential of virus-based nanomaterials to promote endogenous BMP2 production which may prove to be a unique approach to studying the regulatory mechanisms involved in early osteoblastic differentiation. PMID:22532088

Sitasuwan, Pongkwan; Lee, L Andrew; Bo, Peng; Davis, Erin N; Lin, Yuan; Wang, Qian

2012-04-24

2

INFLUENCE OF LEPTIN ON THE EARLY PHASES OF BONE FORMATION DURING MOUSE SKELETON ORGANOGENESIS  

Microsoft Academic Search

Leptin is a 16-kDa hormone, primarily secreted by adipose tissue, which controls body weight through its effects on food intake and energy expenditure by negative feedback at the hypothalamic nuclei. Leptin is now known to have actions in the immune system, reproduction, development, haemopoiesis, angiogenesis and, most recently, in bone metabolism (1). Concerning the skeleton, it seems to be involved

Rivasi Marianna; Benelli Augusta; Ferretti Marzia; Benincasa Marta; Bertoni Laura; Cavani Francesco; Palumbo Carla

2007-01-01

3

Bone formation by cancer metastases  

Microsoft Academic Search

The formation of heterotopic bone tissue in malignant tumors or in their metastases is extremely rare. In a 60 years old male patient with bronchogenic carcinoma (adenocarcinoma) extensive bone formation was observed within multiple metastases in the skeletal muscles. On the basis of the microscopic findings, the mechanism of bone formation by malignant tumors is discussed. Obviously, proliferation of local

U. Bettendorf; W. Remmele; H. Laaff

1976-01-01

4

Bisphosphonates Inhibit Breast and Prostate Carcinoma Cell Invasion, an Early Event in the Formation of Bone Metastases1  

Microsoft Academic Search

The molecular mechanisms by which tumor cells metastasize to bone are likely to involve invasion, cell adhesion to bone, and the release of soluble mediators from tumor cells that stimulate osteoclast-mediated bone resorption. Bisphosphonates (BPs) are powerful inhibitors of the osteoclast activity and are, therefore, used in the treatment of patients with osteolytic metastases. However, an added beneficial effect of

Sandrine Boissier; Mercedes Ferreras; Olivier Peyruchaud; Sandrine Magnetto; Frank H. Ebetino; Marc Colombel; Pierre Delmas; Jean-Marie Delaisse; Philippe Clezardin

5

Dilatational band formation in bone.  

PubMed

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

2012-11-05

6

Localization of tartrate-resistant acid phosphatase (TRAP), membrane type-1 matrix metalloproteinases (MT1-MMP) and macrophages during early endochondral bone formation  

PubMed Central

Endochondral bone formation, the process by which most parts of our skeleton evolve, leads to the establishment of the diaphyseal primary (POC) and epiphyseal secondary ossification centre (SOC) in long bones. An essential event for the development of the SOC is the early generation of vascularized cartilage canals that requires the proteolytic cleavage of the cartilaginous matrix. This in turn will allow the canals to grow into the epiphysis. In the present study we therefore initially investigated which enzymes and types of cells are involved in this process. We have chosen the mouse as an animal model and focused our studies on the distal part of the femur during early stages after birth. The formation of the cartilage canals was promoted by tartrate-resistant acid phosphatase (TRAP) and membrane type-1 matrix metalloproteinases (MT1-MMP). In addition, macrophages and cells containing numerous lysosomes contributed to the establishment of the canals and enabled their further advancement into the epiphysis. As development continued, the SOC was formed, and in mice aged 10 days a distinct layer of type I collagen (= osteoid) was laid down onto the cartilage scaffold. The events leading to the establishment of the SOC were compared with those of the POC. Basically these processes were quite similar, and in both ossification centers, TRAP-positive chondroclasts resorbed the cartilage matrix. However, occasionally co-expression of TRAP and MT1-MMP was noted in a small subpopulation of this cell type. Furthermore, numerous osteoblasts expressed MT1-MMP from the start of endochondral ossification, whereas others did not. In osteocytogenesis, MT1-MMP has been shown to be critical for the establishment of the cytoplasmic processes mediating the communication between osteocytes and bone-lining cells. Considering the well-known fact that not all osteoblasts transform into osteocytes, and in accordance with the present data, we suggest that MT1-MMP is needed at the very beginning of osteocytogenesis and may additionally determine whether an osteoblast further differentiates into an osteocyte.

Blumer, Michael J F; Longato, Stefano; Fritsch, Helga

2008-01-01

7

Identity Formation During Early Adolescence  

Microsoft Academic Search

A special issue of the Journal of Early Adolescence has been prepared to address theoretical and research issues concerning identity formation during early adolescence. The issue has been designed to help direct and stimulate interest in research on identity formation during early adolescence. In these introductory comments the major tenets of Erikson's psychosocial theory of identity formation are outlined, the

Gerald R. Adams; Raymond Montemayor

1983-01-01

8

[Mechanisms for formation of myeloma bone disease].  

PubMed

Myeloma cells stimulate bone resorption by enhancing osteoclast formation and suppress bone formation by inhibiting osteoblast differentiation. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta as well as RANK ligand play a major role in the enhancement of bone resorption in myeloma. Myeloma cell-derived soluble Wnt inhibitors as well as TGF-beta released from the bone tissues through enhanced bone resorption are thought to suppress osteoblast differentiation. Such pathognomonically skewed cellular components in the bone marrow create a microenvironment suitable for myeloma cell growth and survival (a myeloma niche) , which should be targeted to suppress myeloma expansion along with amelioration of bone lesions. PMID:18379024

Yata, Kenichiro; Abe, Masahiro; Matsumoto, Toshio

2008-04-01

9

FORMATION OF BONE TISSUE IN CULTURE FROM ISOLATED BONE CELLS  

Microsoft Academic Search

A system is described for the formation of bone tissue in culture from isolated rat bone cells . The isolated bone cells were obtained from embryonic rat calvarium and perios- teum or from traumatized, lifted periosteum of young rats . The cells were cultured for a period of up to 8 wk, during which time the morphological, biochemical, and functional

ITZHAK BINDERMAN; ARIEH HARELL; EPHRAIM KATZIR; LEO SACHS

1974-01-01

10

Hormonal and Local Regulation of Bone Formation.  

ERIC Educational Resources Information Center

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

Canalis, Ernesto

1985-01-01

11

Bisphosphonates Stimulate Formation of Osteoblast Precursors and Mineralized Nodules in Murine and Human Bone Marrow Cultures In Vitro and Promote Early Osteoblastogenesis in Young and Aged Mice In Vivo  

Microsoft Academic Search

Recent in vitro findings suggest that bisphosphonates, potent inhibitors of osteoclastic bone resorption, may also have a direct action on osteoblasts. The purpose of this study was to search for potential effects of etidronate and alendronate on the formation of early and late osteoblastic cell precursors by measuring the number of colony-forming units for fibroblasts (CFU-F) and colony-forming units for

N Giuliani; M Pedrazzoni; G Negri; G Passeri; M Impicciatore; G Girasole

1998-01-01

12

The early phase influence of bone marrow concentrate on metaphyseal bone healing.  

PubMed

Bone marrow concentrate (BMC) contains high densities of progenitor cells. Therefore, in critical size defects BMC may have the potency to support bone healing. The aim of this study was to investigate the effect of BMC in combination with calcium phosphate granules (CPG) on bone defect healing in a metaphyseal long bone defect in mini-pigs. A metaphyseal critical-size bone defect at the proximal tibia of 24 mini-pigs was filled with CPG combined with BMC, CPG solely (control group) or with an autograft. Radiological and histomorphometrical evaluations after 6 weeks (42 days) showed significantly more bone formation in the BMC group in the central area of the defect zone and the cortical defect zone compared to the CPG group. At the same time the resorption rate of CPG increased significantly in the BMC group. Nevertheless, compared to the BMC group the autograft group showed a significantly higher new bone formation radiologically and histomorphometrically. In BMC the count of mononuclear cells was significantly higher compared to the bone marrow aspirate (3.5-fold). The mesenchymal progenitor cell characteristics of the cells in BMC were confirmed by flow cytometry. Cells from BMC created significantly larger colonies of alkaline phosphatase-positive colony forming units (CFU-ALP) (4.4-fold) compared to cells from bone marrow aspirate. Nevertheless, even in the BMC group complete osseous bridging was only detectable in isolated instances of the bone defects. Within the limitations of this study the BMC+CPG composite promotes bone regeneration in the early phase of bone healing significantly better than the isolated application of CPG. However, the addition of BMC does not lead to a solid fusion of the defect in the early phase of bone healing an still does not represent an equal alternative to autologous bone. PMID:23684350

Jungbluth, P; Hakimi, A R; Grassmann, J P; Schneppendahl, J; Betsch, M; Kröpil, P; Thelen, S; Sager, M; Herten, M; Wild, M; Windolf, J; Hakimi, M

2013-05-14

13

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis.  

PubMed

Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 ?g/day, n?=?45) and risedronate (35 mg/week, n?=?47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients. PMID:23740422

Farahmand, P; Marin, F; Hawkins, F; Möricke, R; Ringe, J D; Glüer, C-C; Papaioannou, N; Minisola, S; Martínez, G; Nolla, J M; Niedhart, C; Guañabens, N; Nuti, R; Martín-Mola, E; Thomasius, F; Peña, J; Graeff, C; Kapetanos, G; Petto, H; Gentzel, A; Reisinger, A; Zysset, P K

2013-06-01

14

Ectopic bone formation in a subsegmental bronchus.  

PubMed

A 48-year-old man with fever and dry cough was admitted to our hospital. Imaging examinations revealed a mass lesion with calcification in the right B(3)b bronchus and atelectasis in the distal lung area. Subsequently, right S(3) segmentectomy was performed. There was a hard polypoid mass completely obstructing the right B(3)b bronchus. Histopathological findings suggested a metaplastic bone formation with mature bone marrow tissue leading to the primary bronchial cartilage. A case of ectopic bone formation in subsegmental bronchus has never been reported thus far. The resident fibroblasts might transform into osteoblasts under appropriate environmental conditions and induce bone formation. PMID:22692702

Tsukioka, Takuma; Yamamoto, Rhoji; Takahama, Makoto; Nakajima, Ryu; Tada, Hirohito

2012-06-13

15

Does simvastatin stimulate bone formation in vivo?  

Microsoft Academic Search

BACKGROUND: Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS) to the known anabolic effects of PTH in an established model of ovariectomized (OVX) Swiss-Webster mice.

Dietrich von Stechow; Susan Fish; Dror Yahalom; Itai Bab; Michael Chorev; Ralph Müller; Joseph M Alexander

2003-01-01

16

Prostaglandin E2 receptors in bone formation  

PubMed Central

Prostaglandins, PGE2 in particular, have diverse actions on various organs, including inflammation, bone healing, bone formation, embryo implantation, induction of labour and vasodilatation, among others. However, systemic side effects have limited their clinical utility. The pharmacological activities of PGE2 are mediated through four G protein-coupled receptor subtypes, EP1–EP4. Recent studies have shown that EP2 and EP4 receptors play important roles in regulating bone formation and resorption. EP2 and EP4 receptor-selective agonists have been shown to stimulate local or systemic bone formation, augment bone mass and accelerate the healing of fractures or bone defects in animal models upon local or systemic administration, thus, potentially offering new therapeutic options for enhancing bone formation and bone repair in humans. This review will focus on the studies related to bone formation and bone healing in the EP receptor knockout (KO) mice and the EP2 or EP4 receptor-selective agonist treated animal models.

Thompson, D. D.

2007-01-01

17

Burn Injury Enhances Bone Formation in Heterotopic Ossification Model.  

PubMed

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

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

2013-05-12

18

Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys ( Macaca fascicularis)  

Microsoft Academic Search

Strontium ranelate (S12911) has previously been shown to stimulate bone formation and inhibit bone resorption in rats. To determine whether strontium ranelate affects normal bone remodeling, we studied the effect of strontium ranelate on alveolar bone in monkeys. Strontium ranelate, at dosages of 100, 275, and 750 mg\\/kg per day, or vehicle, were given by gavage to 31 normal adult

J Buehler; P Chappuis; J. L Saffar; Y Tsouderos; A Vignery

2001-01-01

19

Ameloblastin expression during craniofacial bone formation in rats.  

PubMed

Based on previous results showing the expression of ameloblastin (Ambn; amelin) in the formation of mesenchymal dental hard tissues, we investigated its presence during bone development. Immunohistochemistry (IHC), in situ hybridization (ISH), and reverse transcription-polymerase chain reaction (RT-PCR) were used to investigate the expression of ameloblastin protein and mRNA during craniofacial development in rats. Tissue samples were collected on embryonic day 18 and from days 2-28 postnatally. IHC revealed the expression of ameloblastin during bone formation at embryonic and early postnatal stages with different patterns of expression in intramembranous and endochondral ossification. In intramembranous ossification, ameloblastin expression was detected in the superficial layer of the condensed vascularized primitive connective tissue and in the cellular layer covering the surface of the newly formed woven bone. In endochondral ossification, ameloblastin was expressed within the extracellular matrix of the cartilage templates and in the perichondrium. Between days 2 and 28 the expression decreased markedly, concordant with the maturation of the bone, and disappeared after completion of bone remodeling. The results obtained by IHC were confirmed by ISH and RT-PCR, showing the expression of ameloblastin mRNA during craniofacial bone formation. This study indicates the expression of the putative dental protein ameloblastin during craniofacial bone development in rats. PMID:17184233

Spahr, Axel; Lyngstadaas, Staale P; Slaby, Ivan; Pezeshki, Gita

2006-12-01

20

Clay-Enriched Silk Biomaterials for Bone Formation  

PubMed Central

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

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

2011-01-01

21

The Predictive Value of Biochemical Markers of Bone Turnover for Bone Mineral Density in Early Postmenopausal Women Treated with Hormone Replacement or Calcium Supplementation  

Microsoft Academic Search

To compare the relative sensitivity and specificity of bone turnover indexes for bone loss or gain in early postmenopausal women, we performed a multicenter trial in 236 menopausal women (mean age, 51 yr), who were randomized to hormone replacement therapy (HRT) or calcium supplementation (CS; 500 mg\\/day) for 1 yr. Two markers of bone formation, osteocalcin (OC) and bone alkaline

CLIFFORD J. ROSEN; CHARLES H. CHESNUT; NANCY J. S. MALLINAK

22

EXPERIMENTAL STUDIES ON HETEROPLASTIC BONE FORMATION  

PubMed Central

1. Bone formation in the rabbit kidney with ligated vessels takes place (a) through the activity of young fibroblasts which accumulate to form a membrane-like structure; (b) subsequently by direct ossification of hyaline connective tissue in continuity with preformed bone; and (c) through erosion of lime placques by granulating tissue and laying down of lamellar bone by cells derived from fibroblasts. 2. Bone formation in the rabbit kidney begins not in direct contact with calcium deposits, but in the loose vascular connective tissue close under the transitional epithelium of the calices. 3. With autotransplanted ear cartilage of the rabbit there is an active new formation of cartilage in the connective tissue which surrounds the transplants, and the bone is formed by the fibroblasts from the perichondrium which erode and invade the calcified areas in this new cartilage. 4. The process of bone formation in the kidney is similar to that found in normal membranous ossification, while with the transplanted ear cartilage the process is identical with endochondral ossification.

Asami, Goichi; Dock, William

1920-01-01

23

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

24

Assessing the function of early hominin bone tools  

Microsoft Academic Search

Bone tools from early hominin sites in southern Africa continue to intrigue researchers interested in the development of early human technology and cognition. Sterkfontein, Swartkrans and Drimolen have all yielded bone tools dated to between 1 and 2Mya associated with numerous Paranthropus robustus and few early Homo remains. The bone tools are described by different authors as implements used to

Francesco d'Errico; Lucinda Backwell

2009-01-01

25

Early postoperative bone scintigraphy in the evaluation of microvascular bone grafts in head and neck reconstruction  

Microsoft Academic Search

BACKGROUND: Bone scintigraphy was performed to monitor anastomotic patency and bone viability. METHODS: In this retrospective study, bone scans were carried out during the first three postoperative days in a series of 60 patients who underwent microvascular bone grafting for reconstruction of the mandible or maxilla. RESULTS: In our series, early bone scans detected a compromised vascular supply to the

Jonas Schuepbach; Olivier Dassonville; Gilles Poissonnet; Francois Demard

2007-01-01

26

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

2011-12-28

27

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.

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

28

Early implant bone loss: preventable or inevitable?  

PubMed

Early implant bone loss (EIBL) is defined as the periimplant crestal bone loss occurring from fixture installation to 1 year after loading. This phenomenon has been suggested to be associated with biologic and biomechanical factors. Minimizing EIBL at every treatment step is preferable because this may improve implant health, aesthetics, and overall success. This review presents the host-related factors, implant design characteristics, and the surgical and restorative protocol modifiers that should be evaluated during therapy. Host-related factors may involve the healing capacity, periodontal status, and occlusal function. Implant design features to be considered include the control of biologic width, microgap, and crestal stress distribution. Finally, surgical and restorative factors to be considered are implant site development, minimally invasive surgical approach, implant positioning, and the restorative design and occlusal scheme. Rationale and strategies to control the modifiable factors are also proposed. PMID:22983314

Tatarakis, Nikolaos; Bashutski, Jill; Wang, Hom-Lay; Oh, Tae-Ju

2012-10-01

29

Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass  

PubMed Central

Aging reduces the number of mesenchymal stem cells (MSCs) in the bone marrow which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct the MSCs to the bone surface by attaching a synthetic high affinity and specific peptidomimetic ligand (LLP2A) against integrin ?4?1 on the MSC surface, to a bisphosphonate (alendronate, Ale) that has high affinity for bone. LLP2A-Ale increased MSCs migration and osteogenic differentiation in vitro. A single intravenous injection of LLP2A-Ale increased trabecular bone formation and bone mass in both xenotransplantation and immune competent mice. Additionally, LLP2A-Ale prevented trabecular bone loss after peak bone acquisition was achieved or following estrogen deficiency. These results provide a proof of principle that LLP2A-Ale can direct MSCs to the bone to form new bone and increase bone strength.

Guan, Min; Yao, Wei; Liu, Ruiwu; Lam, Kit S.; Nolta, Jan; Jia, Junjing; Panganiban, Brian; Meng, Liping; Zhou, Ping; Shahnazari, Mohammad; Ritchie, Robert O.; Lane, Nancy E.

2013-01-01

30

Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption  

Microsoft Academic Search

The aims of the study were to evaluate the use of bone-specific biochemical markers of turnover in type I osteoporosis, to test for evidence of heterogeneity of bone turnover in this condition, and to attempt to devise an ‘uncoupling index’ by using the relationship between bone-specific biochemical markers of bone formation and bone resorption. In women with type I osteoporosis

R. Eastell; S. P. Robins; T. Colwell; A. M. A. Assiri; B. L. Riggs; R. G. G. Russell

1993-01-01

31

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

32

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

PubMed

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

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

2001-10-01

33

Distal radial fractures heal by direct woven bone formation  

PubMed Central

Background Descriptions of fracture healing almost exclusively deal with shaft fractures and they often emphasize endochondral bone formation. In reality, most fractures occur in metaphyseal cancellous bone. Apart from a study of vertebral fractures, we have not found any histological description of cancellous bone healing in humans. Patients and methods We studied histological biopsies from the central part of 12 distal radial fractures obtained during surgery 6–28 days after the injury, using routine hematoxylin and eosin staining. Results New bone formation was seen in 6 cases. It was always in the form of fetal-like, disorganized woven bone. It seldom had contact with old trabeculae and appeared to have formed directly in the marrow. Cartilage was scarce or absent. The samples without bone formation showed only necrosis, scar, or old cancellous bone. Interpretation The histology suggests that cells in the midst of the marrow respond to the trauma by direct formation of bone, independently of trabecular surfaces.

2013-01-01

34

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

Feik, S A

1993-01-01

35

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

36

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.

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

2012-01-01

37

Processes Involved in Early Biofilm Formation.  

National Technical Information Service (NTIS)

Results of Series I experiments provided the following information: the rate of biofilm COD accumulation during its early formation stages was described mathematically using a first-order rate expression. The resultant first-order rate constant was a line...

J. D. Bryers

1982-01-01

38

The impact of skeletal unloading on bone formation.  

PubMed

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. PMID:12959131

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

2003-06-01

39

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.

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

2011-01-01

40

Brief review of models of ectopic bone formation.  

PubMed

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

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

2012-01-04

41

Spaceflight results in formation of defective bone.  

PubMed

Growing rats were flown on 19 day spaceflights aboard Cosmos 782 and 936 biosatellites. Spaceflight resulted in a prominent skeletal defect at the periosteal surface of the tibia diaphysis. The defect, termed an arrest line, was approximately 3 micron across and separated the bone formed in space from that formed following spaceflight. The bone matrix at the arrest line region was abnormal in that collagen fibers were preferentially orientated parallel to the periosteal surface. In addition, the bone matrix was hypomineralized. The altered bone was inferior to normal bone in resistance to abrasion and may be partially responsible for the decrease in torsional strength observed after spaceflight. PMID:4080703

Turner, R T; Bell, N H; Duvall, P; Bobyn, J D; Spector, M; Holton, E M; Baylink, D J

1985-12-01

42

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

43

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

44

Stratigraphy and depositional history, Bone Spring Formation, Lea County, New Mexico  

SciTech Connect

The Bone Spring formation of the northern Delaware basin in southeastern New Mexico produces oil in Lea County from foreshelf detrital carbonate facies, such as in Scharb field. Production there comes from several intervals. Stratigraphic correlations between the various Bone Springs units and equivalent Leonardian facies of the Northwest shelf in Lea County suggest that the Bone Spring is correlative to the Yeso Formation of the Northwest shelf. The shelf facies there are divided into lower, middle, and upper Yeso. The upper part of what has generally been considered to be Wolfcamp in some areas, beneath the lowermost Bone Spring sandstone, is inferred to be lower Leonardian (lower Yeso) throughout the area studied. A model is proposed for the sedimentologic and reservoir evolution of the Bone Spring Formation in Lea County. Permian-Pennsylvanian tectonic activity provided the initial substrate for the development of a high-energy shelf edge in early Yeso time. In early middle Yeso time, the basin filled with sediments of the 3rd and 2nd Bone Spring units, and the shelf to basin transition was more subtle. As the basin subsided with infilling, a high-energy shelf edge again developed in late middle Yeso time. With continued basin infilling by 1st Bone Springs facies, the shelf to basin transition again evolved into a more subtle feature. Continued basin subsidence caused infilling by a thick sequence of upper Yeso carbonate, which was capped by progradational shelf carbonates of the upper Yeso.

Mazzullo, L.J. (Nearburg Producing Co., Dallas, TX (USA))

1987-02-01

45

Bone formers: osteophyte and enthesophyte formation are positively associated  

PubMed Central

OBJECTIVE—To test the hypothesis that enthesophyte formation and osteophyte growth are positively associated and to look for associations between bone formation at different sites on the skeleton so that a simple measure of bone formation could be derived.?METHODS—Visual examination of 337 adult skeletons. All common sites of either enthesophyte or osteophyte formation were inspected by a single observer who graded bone formation at these sites on a 0-3 scale. The total score for each feature was divided by the number of sites examined to derive an enthesophyte and an osteophyte score. Cronbach's ? and principal components analysis were used to identify groupings.?RESULTS—Enthesophyte formation was associated with gender (M>F) and age. There was a positive correlation between enthesophytes and osteophytes (r = 0.65, 95% confidence interval, 0.58 to 0.71) which remained after correction for age and gender. Principal components analysis indicated four different groupings of enthesophyte formation. By choosing one site from each group a simple index of total skeletal bone formation could be derived.?CONCLUSIONS—Osteophytes and enthesophytes are associated, such that a proportion of the population can be classified as "bone formers". Enthesophyte groupings provide some clues to aetiopathogenesis. Bone formation should be investigated as a possible determinant of the heterogeneity of outcome and of treatment responses in common musculoskeletal disorders.??

Rogers, J.; Shepstone, L.; Dieppe, P.

1997-01-01

46

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.

Malaval, Luc; Wade-Gueye, Ndeye Marieme; Boudiffa, Maya; Fei, Jia; Zirngibl, Ralph; Chen, Frieda; Laroche, Norbert; Roux, Jean-Paul; Burt-Pichat, Brigitte; Duboeuf, Francois; Boivin, Georges; Jurdic, Pierre; Lafage-Proust, Marie-Helene; Amedee, Joelle; Vico, Laurence; Rossant, Janet; Aubin, Jane E.

2008-01-01

47

Bone Formation by BMP Gene Transfection  

NASA Astrophysics Data System (ADS)

An application of bone morphogenetic proteins (BMPs) has been expected to be a solution for fracture repair and bone regeneration ever since the discovery of their osteogenic potential (Urist, 1965; Reddi, 2000). Recombinant BMPs have been employed in in vitro and in vivo studies of bone induction. In vitro studies have revealed that BMPs cause the transformation of pluripotent mesenchymal cells obtained from bone marrow (Thies et al., 1992), fat (Dragoo et al., 2003), and muscle (Katagiri et al., 1994) into osteogenic cells. Clinical application of recom-binant BMPs requires a high-quality recombinant protein and drug delivery system (DDS), which enables slow and continuous release of protein.

Kishimoto, Koshi N.; Watanabe, Yuji

48

Heterotopic new bone formation causes resorption of the inductive bone matrix  

SciTech Connect

The bone matrix of growing rats was labeled by multiple injections of 3H-proline, and demineralized bone matrix (DBM) was prepared. The DBM was allotransplanted heterotopically into growing rats. New bone formation was induced in and around the implants. The new bone formation was accompanied by a decrease in the content of 3H; 20 and 30 days after implantation, 72% and 46%, respectively, of the activity remained in the implants. Daily injections of indomethacin (2 mg/kg) inhibited calcium uptake by about 20% at 20 and 30 days and inhibited the release of 3H from the DBM to a similar degree. Heterotopic bone induction by DBM is accompanied by matrix resorption, and inhibition of the new bone formation decreases the resorption of DBM.

Nilsson, O.S.; Persson, P.E.; Ekelund, A. (Karolinska Institute and Hospital, Stockholm (Sweden))

1990-08-01

49

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

50

Novel functions for NF?B: inhibition of bone formation  

Microsoft Academic Search

NF?B is a family of transcription factors involved in immunity and the normal functioning of many tissues. It has been well studied in osteoclasts, and new data indicate an important role for NF?B in the negative regulation of bone formation. In this article, we discuss how NF?B activation affects osteoblast function and bone formation. In particular, we describe how reduced

Susan A. Krum; Jia Chang; Gustavo Miranda-Carboni; Cun-Yu Wang

2010-01-01

51

Bone formation in calcium-phosphate-coated titanium mesh.  

PubMed

The osteogenic activity of porous titanium fiber mesh and calcium phosphate (Ca-P)-coated titanium fiber mesh loaded with cultured syngeneic osteogenic cells was compared in a syngeneic rat ectopic assay model. In 30 syngeneic rats, (Ca-P)-coated and non-coated porous titanium implants were subcutaneously placed either without or loaded with cultured rat bone marrow (RBM) cells. Fluorochrome bone markers were injected at 2, 4, and 6 weeks. The rats were sacrificed, and the implants were retrieved at 2, 4, and 8 weeks post-operatively. Histological analysis demonstrated that none of the (Ca-P)-coated and non-coated meshes alone supported bone formation at any time period. In RBM-loaded implants, bone formation started at 2 weeks. At 4 weeks, bone formation increased. However, at 8 weeks bone formation was absent in the non-coated titanium implants, while it had remained in the (Ca-P)-coated titanium implants. Also, in (Ca-P)-coated implants more bone was formed than in non-coated samples. In general, osteogenesis was characterized by the occurrence of multiple spheres in the porosity of the mesh. The accumulation sequence of the fluorochrome markers showed that the newly formed bone was deposited in a centrifugal manner starting at the center of a pore. Our results show that the combination of Ti-mesh with RBM cells can indeed generate bone formation. Further, our results confirm that a thin Ca-P coating can have a beneficial effect on the bone-generating properties of a scaffold material. PMID:10941922

Vehof, J W; Spauwen, P H; Jansen, J A

2000-10-01

52

Engineering bone formation with peptidomimetic hybrid biomaterials.  

PubMed

Bone exhibits hierarchical levels of organization from macroscopic to microscopic, and nano- length scales. Furthermore, multiple bioactive peptides, as part of the collagenous and non-collagenous water soluble glycoproteins and proteoglycans in the bone ECM, interact with progenitor BMS cells to initiate the cascade of chemotaxis, differentiation, and mineralization. In this work, a nanofiber hydrogel/apatite composite matrix is developed to mimic the laminated structure of the osteons in bone and to determine the effect of RGD and BMP peptides, grafted to the composite, on osteogenic differentiation and mineralization of BMS cells. For four-layer laminates, the Young's modulus of the laminated composites was four times that of the nanofibers alone. BMS cells seeded on RGD+BMP peptide modified composites showed synergistic 4.9- and 11.8-fold increase in calcium content from day 7 to 14 and 21. These findings are potentially useful in developing engineered scaffolds for bone regeneration. PMID:19963742

Jabbari, Esmaiel

2009-01-01

53

Lrp5 and bone formation : A serotonin-dependent pathway.  

PubMed

Lrp5, the mutated gene in osteoporosis pseudoglioma (OPPG) and the high bone-mass syndrome (HBM), regulates bone formation, while beta-catenin, the molecular node of Wnt signaling, regulates bone resorption, suggesting that Lrp5 could act in a Wnt-independent manner. Using microarray and conditional gene deletion in mice, we showed that Lrp5 actually enhances bone formation by inhibiting the expression, in duodenum, of tryptophan hydroxylase 1, the rate-limiting enzyme in the serotonin biosynthetic pathway. Accordingly, serotonin circulating levels are high in Lrp5(-/-) mice and OPPG patients but low in HBM patients, and normalizing serum serotonin levels rescues the bone phenotype of the Lrp5(-/-) mice. We also showed that serotonin acts on osteoblasts through the Htr1b receptor and the transcription factor cAMP responsive element binding to inhibit their proliferation. This study shows that Lrp5 acts in gut cells, not in osteoblasts, to control bone formation via a Wnt-independent pathway and identifies a new hormone, serotonin, and a novel endocrine axis regulating bone mass. These findings may have important therapeutic implications for the treatment of low bone-mass disorders. PMID:20392224

Yadav, Vijay K; Ducy, Patricia

2010-03-01

54

Osteogenic Matrix Cell Sheet Transplantation Enhances Early Tendon Graft to Bone Tunnel Healing in Rabbits  

PubMed Central

The objective of this study was to determine whether osteogenic matrix cell sheets (OMCS) could induce bone formation around grafted tendons, thereby enhancing early stage tendon to bone tunnel healing in skeletally mature male Japanese white rabbits. First, the osteogenic potential of rabbit OMCS was evaluated. Then, the OMCS were transplanted into the interface between the grafted tendon and the bone tunnel created at the tibia. Histological assessments and biomechanical tensile testing were performed after 3 weeks. The rabbit OMCS showed high alkaline phosphatase (ALP) activity, positive staining of ALP, and osteogenic potential when transplanted subcutaneously with beta tricalcium phosphate disks. Newly formed bony walls and positive collagen type I staining were seen around the grafted tendon with OMCS transplantation, whereas such bony walls were thinner or less frequent without OMCS transplantation. Micro-computed tomography images showed significantly higher bone volume in the OMCS transplantation group. The pullout strength was significantly higher with OMCS (0.74 ± 0.23?N/mm2) than without OMCS (0.58 ± 0.15?N/mm2). These results show that OMCS enhance early tendon to bone tunnel healing. This method can be applied to cases requiring early tendon to bone tunnel healing after ligament reconstruction surgery.

Uematsu, Kota; Akahane, Manabu; Morita, Yusuke; Ogawa, Munehiro; Ueha, Tomoyuki; Shimizu, Takamasa; Kura, Tomohiko; Kawate, Kenji; Tanaka, Yasuhito

2013-01-01

55

Early structure formation from cosmic string loops  

NASA Astrophysics Data System (ADS)

We examine the effects of cosmic strings on structure formation and on the ionization history of the universe. While Gaussian perturbations from inflation are known to provide the dominant contribution to the large scale structure of the universe, density perturbations due to strings are highly non-Gaussian and can produce nonlinear structures at very early times. This could lead to early star formation and reionization of the universe. We improve on earlier studies of these effects by accounting for high loop velocities and for the filamentary shape of the resulting halos. We find that for string energy scales G?gtrsim10-7, the effect of strings on the CMB temperature and polarization power spectra can be significant and is likely to be detectable by the Planck satellite. We mention shortcomings of the standard cosmological model of galaxy formation which may be remedied with the addition of cosmic strings, and comment on other possible observational implications of early structure formation by strings.

Shlaer, Benjamin; Vilenkin, Alexander; Loeb, Abraham

2012-05-01

56

The progress of early phase bone healing using porous granules produced from calcium phosphate cement  

PubMed Central

Objective Bone grafting is a vital component in many surgical procedures to facilitate the repair of bone defects or fusions. Autologous bone has been the gold standard to date in spite of associated donor-site morbidity and the limited amount of available donor bone. The aim of this study was to investigate the progress of bone regeneration and material degradation of calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder compared to the use of autologous bone grafting in the treatment of "critical size defects" on load-bearing long bones of minipigs. Methods A critical size defect in the tibial metaphysis of 16 mini-pigs was filled either with autologous cancellous graft or with micro- and macroporous carbonated, apatic calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder. After 6 weeks, the specimens were assessed by X-ray and histological evaluation. The amount of new bone formation was analysed histomorphometrically. Results The semi-quantitative analysis of the radiological results showed a complete osseous bridging of the defect in three cases for the autograft group. In the same group five animals showed a beginning, but still incomplete bridging of the defect, whereas in the CPG group just two animals developed this. All other animals of the CPG group showed only a still discontinuous new bone formation. Altogether, radiologically a better osseous bridging was observed in the autograft group compared to the CPG group. Histomorphometrical analysis after six weeks of healing revealed that the area of new bone was significantly greater in the autograft group concerning the central area of the defect zone (p < 0.001) as well as the cortical defect zone (p < 0.002). All defects showed new bone formation, but only in the autograft group defects regenerated entirely Conclusions Within the limits of the present study it could be demonstrated that autologous cancellous grafts lead to a significantly better bone regeneration compared to the application of calcium phosphate granules (CPG) produced from a calcium phosphate self-setting cement powder after 6 weeks. In the early phase of bone-healing, the sole application of CPG appears to be inferior to the autologous cancellous grafts in an in vivo critical size defect on load-bearing long bones of mini-pigs.

2010-01-01

57

Osteoclast formation and bone resorption are inhibited by megakaryocytes  

Microsoft Academic Search

It has been previously reported that addition of megakaryocytes (MKs) to osteoblasts in vitro results in increased osteoblastic collagen and osteoprotegerin (OPG) production, suggesting a role for MKs in bone formation. To further investigate this role, we have studied the effects of MKs on osteoclast formation and activity. Human osteoclasts were generated from CD14 monocytes isolated from peripheral blood and

C. A. Beeton; S. Bord; D. Ireland; J. E. Compston

2006-01-01

58

TGF-? and BMP Signaling in Osteoblast Differentiation and Bone Formation  

PubMed Central

Transforming growth factor-beta (TGF-?)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-?/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-?/BMPs is specifically through both canonical Smad-dependent pathways (TGF-?/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-?/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-?/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-?/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-?/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-?/BMP signaling. This review also highlights the different modes of cross-talk between TGF-?/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.

Chen, Guiqian; Deng, Chuxia; Li, Yi-Ping

2012-01-01

59

TGF-? and BMP signaling in osteoblast differentiation and bone formation.  

PubMed

Transforming growth factor-beta (TGF-?)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-?/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-?/BMPs is specifically through both canonical Smad-dependent pathways (TGF-?/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-?/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-?/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-?/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-?/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-?/BMP signaling. This review also highlights the different modes of cross-talk between TGF-?/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation. PMID:22298955

Chen, Guiqian; Deng, Chuxia; Li, Yi-Ping

2012-01-21

60

Early events in natural resistance to bone marrow transplantation. Use of radiolabeled bone marrow cells  

Microsoft Academic Search

Natural resistance against the proliferation of splenic colony-forming units (CFU-S) is seen in certain combinations of bone marrow donors and irradiated hosts. In order to examine the early events following bone marrow transplantation and to determine whether genetically determined CFU-S repression is due to elimination of the transplanted cells from the spleen or to inhibition of their proliferation, we labeled

GEORGE A. CARLSON; SUSAN T. MARSHALL; AMY KIESCHE

1986-01-01

61

Bone formation induced by BMP-2 in human osteosarcoma cells.  

PubMed

Our previous studies demonstrated that BMP-2 inhibits the tumorigenicity of cancer stem cells identified as cells with high aldehyde dehydrogenase activity (ALDH(br) cells) from the human osteosarcoma cell line OS99-1. We further investigated whether BMP-2 is capable of inducing bone formation in OS99-1 cells. Flow cytometry sorting was used to isolate tumorigenic ALDH(br) and non-tumorigenic ALDH(lo) cells. qRT-PCR was used to quantify the gene expression. A xenograft model was used to verify the bone formation in vivo. There was significantly higher mRNA expression of BMPR1B and BMPR2 in ALDH(lo) cells compared with that in ALDH(br) cells and the BMPR1B expression in ALDH(lo) cells was ~8-fold higher compared to that in ALDHbr cells. BMP-2 was also found to induce higher transcription of osteogenic markers Runx-2, Osterix (Osx), alkaline phosphatase (ALP) and collagen type I in ALDH(lo) cells compared to ALDH(br) cells, which were mediated by the canonical Smad signaling pathway. In vivo, BMP-2 was identified to induce bone formation in both ALDH(br) and ALDH(lo) cells. All animals receiving 1 x 10()4 ALDH(lo) cells treated with 30 µg of BMP-2 per animal showed bone formation within 1-2 weeks after injection in mice. Bone formation induced by BMP-2 in ALDH(lo) cells showed significantly more bone mineral content compared to that in ALDH(br) cells. BMP-2 induces bone formation in heterogeneous osteosarcoma cells and BMP-2 may have a promising therapeutic role for treating human osteosarcoma by inducing differentiation along an osteogenic pathway. PMID:23900689

Wang, Lin; Park, Paul; La Marca, Frank; Than, Khoi; Rahman, Shayan; Lin, Chia-Ying

2013-07-23

62

Bone formation in TiO2 bone scaffolds in extraction sockets of minipigs.  

PubMed

The osteoconductive capacity of TiO(2) scaffolds was investigated by analysing the bone ingrowth into the scaffold structure following their placement into surgically modified extraction sockets in Gottingen minipigs. Non-critical size defects were used in order to ensure sufficient bone regeneration for the evaluation of bone ingrowth to the porous scaffold structure, and sham sites were used as positive control. Microcomputed tomographic analysis revealed 73.6±11.1% of the available scaffold pore space to be occupied by newly formed bone tissue, and the volumetric bone mineral density of the regenerated bone was comparable to that of the native cortical bone. Furthermore, histological evidence of vascularization and the presence of bone lamellae surrounding some of the blood vessels were also observed within the inner regions of the scaffold, indicating that the highly interconnected pore structure of the TiO(2) scaffolds supports unobstructed formation of viable bone tissue within the entire scaffold structure. In addition, bone tissue was found to be in direct contact with 50.0±21.5% of the TiO(2) struts, demonstrating the good biocompatibility and osteoconductivity of the scaffold material. PMID:22395069

Tiainen, Hanna; Wohlfahrt, Johan Caspar; Verket, Anders; Lyngstadaas, S Petter; Haugen, Håvard J

2012-03-03

63

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

64

Strontium ranelate: a novel mode of action optimizing bone formation and resorption  

Microsoft Academic Search

Strontium ranelate has been shown to decrease the risk of fractures in postmenopausal women. Its efficacy in clinical studies results from its unique mode of action, on both bone resorption and bone formation. Pharmacological studies in animals have shown that strontium ranelate decreases bone resorption and increases bone formation, resulting in increased bone mass. In ovariectomized rats, strontium ranelate prevented

P. J. Marie

2005-01-01

65

Bone density, strength, and formation in adult cathepsin K (-/-) mice.  

PubMed

Cathepsin K (CatK) is a cysteine protease expressed predominantly in osteoclasts, that plays a prominent role in degrading Type I collagen. Growing CatK null mice have osteopetrosis associated with a reduced ability to degrade bone matrix. Bone strength and histomorphometric endpoints in young adult CatK null mice aged more than 10 weeks have not been studied. The purpose of this paper is to describe bone mass, strength, resorption, and formation in young adult CatK null mice. In male and female wild-type (WT), heterozygous, and homozygous CatK null mice (total N=50) aged 19 weeks, in-life double fluorochrome labeling was performed. Right femurs and lumbar vertebral bodies 1-3 (LV) were evaluated by dual-energy X-ray absorptiometry (DXA) for bone mineral content (BMC) and bone mineral density (BMD). The trabecular region of the femur and the cortical region of the tibia were evaluated by histomorphometry. The left femur and sixth lumbar vertebral body were tested biomechanically. CatK (-/-) mice show higher BMD at the central and distal femur. Central femur ultimate load was positively influenced by genotype, and was positively correlated with both cortical area and BMC. Lumbar vertebral body ultimate load was also positively correlated to BMC. Genotype did not influence the relationship of ultimate load to BMC in either the central femur or vertebral body. CatK (-/-) mice had less lamellar cortical bone than WT mice. Higher bone volume, trabecular thickness, and trabecular number were observed at the distal femur in CatK (-/-) mice. Smaller marrow cavities were also present at the central femur of CatK (-/-) mice. CatK (-/-) mice exhibited greater trabecular mineralizing surface, associated with normal volume-based formation of trabecular bone. Adult CatK (-/-) mice have higher bone mass in both cortical and cancellous regions than WT mice. Though no direct measures of bone resorption rate were made, the higher cortical bone quantity is associated with a smaller marrow cavity and increased retention of non-lamellar bone, signs of decreased endocortical resorption. The relationship of bone strength to BMC does not differ with genotype, indicating the presence of bone tissue of normal quality in the absence of CatK. PMID:18845279

Pennypacker, B; Shea, M; Liu, Q; Masarachia, P; Saftig, P; Rodan, S; Rodan, G; Kimmel, D

2008-09-19

66

Diabetes Enhances Periodontal Bone Loss through Enhanced Resorption and Diminished Bone Formation  

PubMed Central

Using a ligature-induced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated whether diabetes primarily affects periodontitis by enhancing bone loss or by limiting osseous repair. Diabetes increased the intensity and duration of the inflammatory infiltrate (P < 0.05). The formation of osteoclasts and percent eroded bone after 7 days of ligature placement was similar, while four days after removal of ligatures, the type 2 diabetic group had significantly higher osteoclast numbers and activity (P < 0.05). The amount of new bone formation following resorption was 2.4- to 2.9- fold higher in normoglycemic vs. diabetic rats (P < 0.05). Diabetes also increased apoptosis and decreased the number of bone-lining cells, osteoblasts, and periodontal ligament fibroblasts (P < 0.05). Thus, diabetes caused a more persistent inflammatory response, greater loss of attachment and more alveolar bone resorption, and impaired new bone formation. The latter may be affected by increased apoptosis of bone-lining and PDL cells.

Liu, R.; Bal, H.S.; Desta, T.; Krothapalli, N.; Alyassi, M.; Luan, Q.; Graves, D.T.

2008-01-01

67

Bone mineral density in nonsteroid treated early rheumatoid arthritis.  

PubMed Central

OBJECTIVES--To determine whether significant reduction in bone mass is detectable in early disease in patients with rheumatoid arthritis (RA) and to examine the possible influences of disease activity and physical disability on bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN). METHODS--LS and FN BMD values were measured and Z scores determined in a cross-sectional study of 104 patients with RA of less than five years duration. BMD values were also compared between a subgroup of 64 patients and a normal control group matched for age, sex, menopausal status and body mass. BMD values and Z scores were correlated with disease activity, measured by the Stoke Index, disability, measured by HAQ score, and disease duration. RESULTS--Premenopausal female patients with RA had significantly reduced mean FN Z scores (-0.62, 95% CI -0.30 to -0.94) which correlated with HAQ scores (Rs 0.358, p = 0.05) and age (Rs 0.397, p = 0.03). There were no significant changes of BMD in males or postmenopausal females. Disease duration and disease activity did not correlate with BMD changes. CONCLUSION--BMD is reduced in premenopausal female patients with early RA possibly related to the attainment of peak bone mass. No significant reduction of BMD was found in males or postmenopausal females with early disease. Physical disability but not disease activity appears to play a role in the reduction of FN bone mass.

Shenstone, B D; Mahmoud, A; Woodward, R; Elvins, D; Palmer, R; Ring, F; Bhalla, A K

1994-01-01

68

Inhibition of Microtubule Assembly in Osteoblasts Stimulates Bone Morphogenetic Protein 2 Expression and Bone Formation through Transcription Factor Gli2  

Microsoft Academic Search

Bone morphogenetic protein 2 (BMP-2) is essential for postnatal bone formation and fracture repair. By screening chemical libraries for BMP-2 mimics using a cell-based assay, we identified inhibitors of microtubule assembly as stimulators of BMP-2 transcription. These microtubule inhibitors increased osteoblast differen- tiation in vitro, stimulated periosteal bone formation when injected locally over murine calvaria, and enhanced trabecular bone formation

Ming Zhao; Seon-Yle Ko; Jin-Hua Liu; Di Chen; Jianghong Zhang; Baolin Wang; Stephen E. Harris; Babatunde O. Oyajobi; Gregory R. Mundy

2009-01-01

69

The Silicone Bone Cap. Bone Contouring and the Control of Adventitious Bone Formation Following Skeletal Surgery.  

National Technical Information Service (NTIS)

Isolation of terminal segments of the transected cat fibula with silicone polymer implants (93 silicone rubber caps implanted in 40 adult cats) resulted in healing at the ends of the bone segments with their intact intermedullary blood supply. Mature bone...

R. Lusskin

1970-01-01

70

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

71

Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass  

Microsoft Academic Search

Aging reduces the number of mesenchymal stem cells (MSCs) that can differentiate into osteoblasts in the bone marrow, which leads to impairment of osteogenesis. However, if MSCs could be directed toward osteogenic differentiation, they could be a viable therapeutic option for bone regeneration. We have developed a method to direct MSCs to the bone surface by attaching a synthetic high-affinity

Min Guan; Ruiwu Liu; Kit S Lam; Jan Nolta; Junjing Jia; Brian Panganiban; Liping Meng; Ping Zhou; Mohammad Shahnazari; Robert O Ritchie; Wei Yao

2012-01-01

72

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

73

Formation of galaxies in the early universe  

NASA Astrophysics Data System (ADS)

We study the formation of galaxies in the early universe for masses 109 - 1012 solar mass. We study in particular the role of nonspherical collapse and rotation on the epoch of galaxy formation. We begin the calculation at the recombination era and take into account the physical processes: expansion of the universe, photo-drag, recombination, photoionization, collisional-ionization, photon-cooling, and hydrogen molecular production, destruction and cooling. For the standard isothermal density perturbation spectrum studied by de Araujo & Opher and Gott & Rees, we obtain, for example for M = 1011 solar mass, the collapse redshifts zc = 0.76 - 1.72 for eccentricities between zero and 0.866. We argue that the natural way to explain why galaxies have a maximum mass is that the maximum mass is a natural result of the existence of the primordial perturbation spectrum. The maximum mass that we find is on the order of observed galactic masses M approximately 1011 solar mass.

de Araujo, J. C. N.; Opher, R.

1994-12-01

74

Bone-specific alkaline phosphatase as a good indicator of bone formation in sheepdogs  

Microsoft Academic Search

Eight clinically healthy male sheepdogs were selected and subjected to experimental radius transaction. Blood samples were\\u000a taken before and weekly after surgery, and radiographs were taken immediately and weekly after surgery to trace new bone formation.\\u000a Total protein, total ALP, and bone-specific ALP were measured in serum samples. There was no significant difference in total\\u000a proteins, but total ALP and

A. R. Mohamadnia; H. R. Shahbazkia; S. Sharifi; I. Shafaei

2007-01-01

75

The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro  

Microsoft Academic Search

In this study, we have determined the effect of the divalent strontium salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3H-thymidine for the last 6 h of culture or treated with S12911 for

E. Canalis; M. Hott; P. Deloffre; Y. Tsouderos; P. J. Marie

1996-01-01

76

Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering  

PubMed Central

Mesenchymal stem/stromal cells (MSC) are typically used to generate bone tissue by a process resembling intramembranous ossification, i.e., by direct osteoblastic differentiation. However, most bones develop by endochondral ossification, i.e., via remodeling of hypertrophic cartilaginous templates. To date, endochondral bone formation has not been reproduced using human, clinically compliant cell sources. Here, we aimed at engineering tissues from bone marrow-derived, adult human MSC with an intrinsic capacity to undergo endochondral ossification. By analogy to embryonic limb development, we hypothesized that successful execution of the endochondral program depends on the initial formation of hypertrophic cartilaginous templates. Human MSC, subcutaneously implanted into nude mice at various stages of chondrogenic differentiation, formed bone trabeculae only when they had developed in vitro hypertrophic tissue structures. Advanced maturation in vitro resulted in accelerated formation of larger bony tissues. The underlying morphogenetic process was structurally and molecularly similar to the temporal and spatial progression of limb bone development in embryos. In particular, Indian hedgehog signaling was activated at early stages and required for the in vitro formation of hypertrophic cartilage. Subsequent development of a bony collar in vivo was followed by vascularization, osteoclastic resorption of the cartilage template, and appearance of hematopoietic foci. This study reveals the capacity of human MSC to generate bone tissue via an endochondral program and provides a valid model to study mechanisms governing bone development. Most importantly, this process could generate advanced grafts for bone regeneration by invoking a “developmental engineering” paradigm.

Barbero, Andrea; Martin, Ivan

2010-01-01

77

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

PubMed

Bone morphogenetic protein 11 (BMP11) is a key regulatory protein in skeletal development. BMP11 propeptide has been shown to antagonize GDF11 activity in vitro. To explore the role of BMP11 propeptide in skeletal formation in vivo, we generated transgenic mice with skeleton-specific overexpression of BMP11 propeptide cDNA. The mice showed a transformation of the seventh cervical vertebra into a thoracic vertebra in our previous report. Presently, further characterizations of the transgenic mice indicated that ossification in calvatia was dramatically enhanced in transgenic fetuses at 16.5 dpc in comparison with their wild-type littermates. At 10 weeks of age, bone mineral content and bone mineral density were significantly (P<0.05) higher in transgenic mice than that in their wild-type littermates based on dual energy X-ray absorptiometry analysis. The relative trabecular bone volume measured by histological analysis was dramatically increased in transgenic mice compared with their wild-type littermates. The enhanced bone formations in the transgenic mice appear to result from increase osteoblast activities as the expressions of four osteoblast markers - ?1 type 1 collagen, osteocalcin, alkaline phosphatase and phex were significantly higher in transgenic fetuses than that in their wild-type littermates. These results suggest that over-expression of BMP11 propeptide stimulates bone formation by increasing osteoblast cell functions. PMID:22093826

Li, Zicong; Zeng, Fang; Mitchell, Alva D; Kim, Yong Soo; Wu, Zhenfang; Yang, Jinzeng

2011-11-10

78

Formation, mineralization, and resorption of bone in hypophosphatemic rats  

PubMed Central

Quantitative morphologic methods were used to measure the effects of feeding a low phosphorus diet to intact and thyroparathyroidectomized rats on several processes of bone mineralization and turnover. In severely hypophosphatemic animals, the matrix formation rate was decreased, the osteoid maturation rate was decreased, which indicated a delay in the onset of mineralization, the initial rate of mineralization was decreased, and the endosteal osteoclastic bone resorption rate was increased. In moderately hypophosphatemic animals, there was a substantial increase in bone resorption but no change in formation or in mineralization. The increase in endosteal bone resorption was due to an increase in the linear rate of bone resorption and particularly to an increase in the length of the endosteal resorbing surface. The magnitude of the increase in bone resorption was similar in thyroparathyroidectomized and intact rats indicating that neither parathyroid hormone nor calcitonin is involved in this change. This, together with the finding that there was a strong negative correlation (r = -0.99) between the per cent endosteal resorbing surface and the serum phosphorus, supports the view that the increased resorption was due to hypophosphatemia. This inverse relationship between endosteal resorbing surface and serum phosphorus appeared to hold for values of serum phosphorus above normal. The resorptive response to hypophosphatemia, as previously shown for the resorptive response to excess endogenous parathyroid hormone, was partially inhibited by vitamin D deficiency. Increased resorption occurred at levels of serum phosphorus where no changes were observed in bone formation, mineralization, or growth, suggesting that this resorptive response functions as a homeostatic mechanism to maintain serum and intracellular phosphorus concentrations. Images

Baylink, D.; Wergedal, J.; Stauffer, M.

1971-01-01

79

Remodeling of Actin Cytoskeleton in Mouse Periosteal Cells under Mechanical Loading Induces Periosteal Cell Proliferation during Bone Formation  

PubMed Central

Background The adaptive nature of bone formation under mechanical loading is well known; however, the molecular and cellular mechanisms in vivo of mechanical loading in bone formation are not fully understood. To investigate both mechanisms at the early response against mechanotransduction in vivo, we employed a noninvasive 3-point bone bending method for mouse tibiae. It is important to investigate periosteal woven bone formation to elucidate the adaptive nature against mechanical stress. We hypothesize that cell morphological alteration at the early stage of mechanical loading is essential for bone formation in vivo. Principal Findings We found the significant bone formation on the bone surface subjected to change of the stress toward compression by this method. The histological analysis revealed the proliferation of periosteal cells, and we successively observed the appearance of ALP-positive osteoblasts and increase of mature BMP-2, resulting in woven bone formation in the hypertrophic area. To investigate the mechanism underlying the response to mechanical loading at the molecular level, we established an in-situ immunofluorescence imaging method to visualize molecules in these periosteal cells, and with it examined their cytoskeletal actin and nuclei and the extracellular matrix proteins produced by them. The results demonstrated that the actin cytoskeleton of the periosteal cells was disorganized, and the shapes of their nuclei were drastically changed, under the mechanical loading. Moreover, the disorganized actin cytoskeleton was reorganized after release from the load. Further, inhibition of onset of the actin remodeling blocked the proliferation of the periosteal cells. Conclusions These results suggest that the structural change in cell shape via disorganization and remodeling of the actin cytoskeleton played an important role in the mechanical loading-dependent proliferation of cells in the periosteum during bone formation.

Sakai, Daisuke; Kii, Isao; Nakagawa, Kazuki; Matsumoto, Hiroko N.; Takahashi, Masateru; Yoshida, Suguru; Hosoya, Takamitsu; Takakuda, Kazuo; Kudo, Akira

2011-01-01

80

Early Growth Response Gene 1 Regulates Bone Properties in Mice  

Microsoft Academic Search

Transcriptional regulation of the postnatal skeleton is incompletely understood. Here, we determined the consequence of loss\\u000a of early growth response gene 1 (EGR-1) on bone properties. Analyses were performed on both the microscopic and molecular\\u000a levels utilizing micro-computed tomography (micro-CT) and Fourier transform infrared imaging (FTIRI), respectively. Mice deficient\\u000a in EGR-1 (Egr-1\\u000a ?\\/?) were studied and compared to sex- and

Marie K. Reumann; Olga Strachna; Lyudmila Lukashova; Kostas Verdelis; Eve Donnelly; Adele L. Boskey; Philipp Mayer-Kuckuk

2011-01-01

81

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

PubMed Central

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

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

2011-01-01

82

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

83

AMP-activated protein kinase (AMPK) activation regulates in vitro bone formation and bone mass  

PubMed Central

Adenosine 5?-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cultured in the presence of AMPK activators (AICAR and metformin), AMPK inhibitor (compound C), the gastric peptide hormone ghrelin and the beta-adrenergic blocker propranolol. AMPK activity was measured in cell lysates by a functional kinase assay and AMPK protein phosphorylation was studied by Western Blotting using an antibody recognizing AMPK Thr-172 residue. We demonstrated that treatment of ROS 17/2.8 cells with AICAR and metformin stimulates Thr-172 phosphorylation of AMPK and dose-dependently increases its activity. In contrast, treatment of ROS 17/2.8 cells with compound C inhibited AMPK phosphorylation. Ghrelin and propranolol dose-dependently increased AMPK phosphorylation and activity. Cell proliferation and alkaline phosphatase activity were not affected by metformin treatment while AICAR significantly inhibited ROS 17/2.8 cell proliferation and alkaline phosphatase activity at high concentrations. To study the effect of AMPK activation on bone formation in vitro, primary osteoblasts obtained from rat calvaria were cultured for 14-17 days in the presence of AICAR, metformin and compound C. Formation of ‘trabecular-shaped’ bone nodules was evaluated following alizarin red staining. We demonstrated that both AICAR and metformin dose-dependently increase trabecular bone nodule formation, while compound C inhibits bone formation. When primary osteoblasts were co-treated with AICAR and compound C, compound C suppressed the stimulatory effect of AICAR on bone nodule formation. AMPK is a ??? heterotrimer, where ? is the catalytic subunit. RT-PCR analysis of AMPK subunits in ROS17/2.8 osteoblastic cells and in mouse tibia showed that the AMPK?1 subunit is the dominant isoform expressed in bone. We analysed the bone phenotype of 4 month-old male wild type (WT) and AMPK?1?/? KO mice using micro-CT. Both cortical and trabecular bone compartments were smaller in the AMPK ?1-deficient mice compared to the WT mice. Altogether, our data support a role for AMPK signalling in skeletal physiology.

Shah, M.; Kola, B.; Bataveljic, A.; Arnett, T.R.; Viollet, B.; Saxon, L.; Korbonits, M.; Chenu, C.

2013-01-01

84

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

PubMed

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 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. PMID:3332556

Thomsen, K; Riis, B; Christiansen, C

1986-12-01

85

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

86

Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey.  

PubMed

Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K (CatK). Previously, ODN was shown to increase bone mineral density (BMD) and maintained normal bone strength at the spine in ovariectomized (OVX) rhesus monkeys. Here, we further characterize the effects of ODN on BMD, bone strength, and dynamic histomorphometric analyses of the hip from the same monkeys. Animals were treated for 21 months with vehicle, 6 or 30 mg/kg ODN (p.o., q.d.). ODN increased femoral neck (FN) BMD by 11% and 15% (p < 0.07) and ultimate load by 25% (p < 0.05) and 30% (p < 0.01) versus vehicle. Treatment-related increases in ultimate load positively correlated with the increased FN BMD, bone mineral content (BMC), and cortical thickness. Histomorphometry of FN and proximal femur (PF) revealed that ODN reduced trabecular and intracortical bone formation rate (BFR) but did not affect long-term endocortical BFR. Moreover, ODN stimulated long-term FN and PF periosteal BFR by 3.5-fold and 6-fold with the 30 mg/kg dose versus vehicle, respectively. Osteoclast surfaces were either unaffected or trended higher (~twofold) in endocortical and trabecular surfaces in the ODN group. Lastly, ODN increased cortical thickness of FN by 21% (p = 0.08) and PF by 19% (p < 0.05) versus vehicle after 21 months of treatment. Together, both doses of ODN increased bone mass and improved bone strength at the hip. Unlike conventional antiresorptives, ODN displayed site-specific effects on trabecular versus cortical bone formation. The drug provided marked increases in periosteal bone formation and cortical thickness in OVX monkeys, suggesting that CatK inhibition may represent a novel therapeutic approach for the treatment of osteoporosis. PMID:22113921

Cusick, Tara; Chen, Charles M; Pennypacker, Brenda L; Pickarski, Maureen; Kimmel, Donald B; Scott, Boyd B; Duong, Le T

2012-03-01

87

Evidence that increased calcium intake does not prevent early postmenopausal bone loss  

Microsoft Academic Search

Calcium's ability to prevent bone loss in early postmenopausal women is controversial. We used data on 394 women from the placebo group of the Early Postmenopausal Interventional Cohort study, a clinical trial of alendronate, to investigate the relation of calcium intake to bone loss. Calcium intake was recorded, and bone mineral density (BMD) (in the lumbar spine, total body, forearm,

David J. Hosking; Philip D. Ross; Desmond E. Thompson; Richard D. Wasnich; Michael McClung; Nina H. Bjarnason; Pernille Ravn; Giovanni Cizza; Marianne Daley; A. John Yates

1998-01-01

88

Profilin1 Regulates Sternum Development and Endochondral Bone Formation  

PubMed Central

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

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

2012-01-01

89

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

90

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.

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

2013-01-01

91

BMP-13 Emerges as a Potential Inhibitor of Bone Formation  

PubMed Central

Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation.

Shen, Bojiang; Bhargav, Divya; Wei, Aiqun; Williams, Lisa A; Tao, Helen; Ma, David D F; Diwan, Ashish D

2009-01-01

92

Multi-protein Delivery by Nanodiamonds Promotes Bone Formation.  

PubMed

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

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

2013-09-17

93

Control of bone formation by the serpentine receptor Frizzled-9  

PubMed Central

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

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

2011-01-01

94

Improving bone formation in a rat femur segmental defect by controlling bone morphogenetic protein-2 release.  

PubMed

Nonunion is a common complication in open fractures and other severe bone injuries. Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on a collagen sponge enhances healing of fractures. However, the burst release of rhBMP-2 necessitates supra-physiological doses of rhBMP-2 to achieve a robust osteogenic effect, which introduces risk of ectopic bone formation and severe inflammation and increases the cost. Although the concept that the ideal pharmacokinetics for rhBMP-2 includes both a burst and sustained release is generally accepted, investigations into the effects of the release kinetics on new bone formation are limited. In the present study, biodegradable polyurethane (PUR) and PUR/microsphere [PUR/poly(lactic-co-glycolic acid)] composite scaffolds with varying rhBMP-2 release kinetics were compared to the collagen sponge delivery system in a critical-sized rat segmental defect model. Microcomputed tomography analysis indicated that a burst followed by a sustained release of rhBMP-2 from the PUR scaffolds regenerated 50% more new bone than the collagen sponge loaded with rhBMP-2, whereas a sustained release without the burst did not form significantly more bone than the scaffold without rhBMP-2. This study demonstrated that the putative optimal release profile (i.e., burst followed by sustained release) for rhBMP-2 can be achieved using PUR scaffolds, and that this enhanced pharmacokinetics regenerated more bone than the clinically available standard of care in a critical-sized defect in rat femora. PMID:21338268

Brown, Kate V; Li, Bing; Guda, Teja; Perrien, Daniel S; Guelcher, Scott A; Wenke, Joseph C

2011-04-03

95

The collagen component of biological bone graft substitutes promotes ectopic bone formation by human mesenchymal stem cells.  

PubMed

Synthetic bone substitutes are attractive materials for repairing a variety of bone defects. They are readily available in unlimited quantities, have a defined composition without batch variability and bear no risk of disease transmission. When combined with mesenchymal stem cells (MSCs), bone healing can be further enhanced due to the osteogenic potential of these cells. However, human MSCs showed considerable donor variability in ectopic bone formation assays on synthetic bone substitutes, which may limit clinical success. This study addresses whether bone formation variability of MSCs is cell-intrinsic or biomaterial-dependent and may be improved using biological bone substitutes with and without collagen. Ectopic bone formation of MSCs from nine donors was tested in immune-deficient mice on biological bone substitutes of bovine and equine origin, containing collagen (bHA-C; eHA-C) or not (bHA; eHA). Synthetic ?-TCP was used for comparison. Histology of 8-week explants demonstrated a significant influence of the bone graft substitute (BGS) on donor variability of ectopic bone formation with best results seen for eHA-C (15/17) and ?-TCP (16/18). Bone was of human origin in all groups according to species-specific in situ hybridization, but MSCs from one donor formed no bone with any bone substitute. According to histomorphometry, most neo-bone was formed on eHA-C with significant differences to bHA, eHA and ?-TCP (p<0.001). Collagen-free biological BGSs were inferior to biological BGSs with collagen (p<0.001), while species-origin was of little influence. In conclusion, BGS composition had a strong influence on ectopic bone formation ability of MSCs, and biological BGSs with a collagen component seem most promising to display the strong osteogenic potential of MSCs. PMID:23542556

Wagner-Ecker, Mechthild; Voltz, Pia; Egermann, Marcus; Richter, Wiltrud

2013-03-28

96

Differentiation of osteoblasts and formation of mineralized bone in vitro  

Microsoft Academic Search

Summary  Periostea consisting of the osteogenic layer and the fibrous layer of the periosteum were dissected from 17-day-old embryonic\\u000a chick calvariae, leaving the osteoblasts behind on bone. The dissected periostea were folded with the osteogenic cells in\\u000a apposition. The explants were cultured on plasma clots for up to 6 days, during which time osteodifferentiation was observed\\u000a followed by osteoid formation in

H. C. Tenenbaum; J. N. M. Heersche

1982-01-01

97

BMP-7 in combination with estrogen enhances bone formation in a fracture callus explant culture.  

PubMed

In postmenopausal women, estrogen withdrawal results in decrease in bone density or osteoporosis. Osteoporosis leads to fracture and retards bone-healing response. Bone morphogenetic protein-7 (BMP-7), a member of the transforming-growth factor-beta superfamily, has been shown as a promising candidate that stimulates bone growth in its application to fracture healing. The purpose of this study was to determine whether BMP-7 could enhance bone formation in the absence of estrogen. Female rats underwent a controlled closed fracture at the midshaft of the right femur. The callus tissues were harvested from the fracture site eight days following the fracture, and were cultured in serum-free media. The explanted callus tissues were then treated with BMP-7, estrogen (E2) or both. We assessed bone formation by measuring alkaline phosphatase (AP) activity, expression of an osteogenic transcription factor, Runt-related transcription factor-2 (Runx2), production of nitric oxide (NO), and calcium mineralization. Supplementation of serum-free cultures with BMP-7 alone increased cell proliferation by twofold, caused a 6.5-fold increase in AP activity, and enhanced calcium mineralization after 48 h. Moreover, BMP-7 in combination with E2 caused a 8.2-fold increase in the AP activity. Runx2 protein expression was increased following stimulation with BMP-7 and E2. Interestingly, E2 induced the amount of NO production by twofold, whereas BMP-7 did not, either alone or with E2. Thus, BMP-7 could enhance early and late markers of bone fracture healing in callus explant cultures, except for NO. BMP-7 could be a promising growth factor in the treatment of fractures as a consequence of osteoporosis. PMID:20453459

Wei, Aiqun; Leong, Anthony; Williams, Lisa; Chung, Sylvia; Shen, Bojiang; Bhargav, Divya; Diwan, Ashish D

2010-05-01

98

How strontium ranelate, via opposite effects on bone resorption and formation, prevents osteoporosis  

Microsoft Academic Search

Oestrogen deficiency increases the rate of bone remodelling which, in association with a negative remodelling balance (resorption\\u000a exceeding formation), results in impaired bone architecture, mass and strength. Current anti-osteoporotic drugs act on bone\\u000a remodelling by inhibiting bone resorption or by promoting its formation. An alternative therapeutic approach is based on the\\u000a concept of inducing opposite effects on bone resorption and

P. J. Marie; D. Felsenberg; M. L. Brandi

2011-01-01

99

Hyperbaric oxygen therapy suppresses osteoclast formation and bone resorption.  

PubMed

The cellular and molecular mechanism through which hyperbaric oxygen therapy (HBO) improves osteonecrosis (ON) is unclear. The present study therefore examined the effect of HBO, pressure and hyperoxia on RANKL-induced osteoclast formation in RAW 264.7 cells and human peripheral blood monocytes (PBMC). Daily exposure to HBO (2.4 ATA, 97% O2 , 90?min), hyperbaric pressure (2.4 ATA, 8.8% O2 , 90?min) or normobaric hyperoxia (1 ATA, 95% O2 , 90?min) significantly decreased RANKL-induced osteoclast formation and bone resorption in normoxic conditions. HBO had a more pronounced anti-osteoclastic effect than hyperoxia or pressure alone and also directly inhibited osteoclast formation and resorption in hypoxic conditions a hallmark of many osteolytic skeletal disorders. The suppressive action of HBO was at least in part mediated through a reduction in RANK, NFATc1, and Dc-STAMP expression and inhibition of hypoxia-induced HIF-1? mRNA and protein expression. This data provides mechanistic evidence supporting the use of HBO as an adjunctive therapy to prevent osteoclast formation and bone loss associated with low oxygen partial pressure. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1839-1844, 2013. PMID:23878004

Hadi, Hadil Al; Smerdon, Gary R; Fox, Simon W

2013-07-22

100

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

PubMed Central

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

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

2009-01-01

101

Coating of titanium with hydroxyapatite leads to decreased bone formation  

PubMed Central

Objectives An experimental rabbit model was used to test the null hypothesis, that there is no difference in new bone formation around uncoated titanium discs compared with coated titanium discs when implanted into the muscles of rabbits. Methods A total of three titanium discs with different surface and coating (1, porous coating; 2, porous coating + Bonemaster (Biomet); and 3, porous coating + plasma-sprayed hydroxyapatite) were implanted in 12 female rabbits. Six animals were killed after six weeks and the remaining six were killed after 12 weeks. The implants with surrounding tissues were embedded in methyl methacrylate and grinded sections were stained with Masson-Goldners trichrome and examined by light microscopy of coded sections. Results Small amounts of bone were observed scattered along the surface of five of the 12 implants coated with porous titanium, and around one out of 12 porous coated surfaces with Bonemaster. No bone formation could be detected around porous coated implants with plasma-sprayed hydroxyapatite. Conclusion Porous titanium coating is to some degree osteoinductive in muscles.

B?e, B. G.; St?en, R. ?.; Solberg, L. B.; Reinholt, F. P.; Ellingsen, J. E.; Nordsletten, L.

2012-01-01

102

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.

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

2011-01-01

103

Serum alkaline phosphatase as an indicator of heterotopic bone formation following total hip arthroplasty.  

PubMed

Serum alkaline phosphatase (SAP) was analyzed in 193 patients treated with total hip arthroplasty (THA) and correlated with the degree of heterotopic bone formation (HBF) one year after surgery. The influence of indomethacin on changes in SAP related to the development of heterotopic bone was studied. Ninety-eight patients received 25 mg of indomethacin three times daily for the first six postoperative weeks; the remaining 95 patients received a placebo treatment. No further anti-inflammatory drugs were allowed during the six weeks. SAP was measured preoperatively and six weeks and 12 weeks after surgery. No patients at risk for developing heterotopic bone after THA could be identified from the preoperative level of SAP. The level of SAP six weeks after THA gradually increased with the amount of HBF. A rise in SAP above 250 IU/liter 12 weeks after surgery was associated with the development of severe heterotopic bone in 13 of 17 patients. Indomethacin inhibited the development of heterotopic bone associated with a rise in SAP following THA. Future studies on HBF and SAP following THA should include information on patient use of anti-inflammatory drugs in the early postoperative period. PMID:3136963

Kjaersgaard-Andersen, P; Pedersen, P; Kristensen, S S; Schmidt, S A; Pedersen, N W

1988-09-01

104

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

105

Biologic determinants of bone formation for osseointegration: Clues for future clinical improvements  

Microsoft Academic Search

Statement of problem. Further improvement in and expansion of the application of dental implants requires control and improvement of bone mass for implant support.Purpose. Although osseointegration involves both the formation and the maintenance of bone at implant surfaces, the aim of this article is to identify cellular and molecular determinants of bone formation that may be used in clinical attempts

Lyndon F. Cooper

1998-01-01

106

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

107

Stochastic star formation and early galactic nucleosynthesis  

NASA Astrophysics Data System (ADS)

We discuss calculations of the star formation, nucleosynthesis, and stochastic evolution of proto-galactic clouds in a galactic chemical evolution model which is motivated by cold dark matter simulations of hierarchical galaxy formation (Saleh et al. 2006; Lan et al. 2010). We utilize SN-induced and dark matter halo formation-induced star formation within a model that follows the evolution of chemical enrichment and energy input to the clouds via Type II, Ia supernovae and stellar winds.

Nguyen, Lan; Mathews, Grant

2013-03-01

108

Early stages of massive star formation  

NASA Astrophysics Data System (ADS)

The formation processes of high-mass stars are not well understood, and the basic question can be phrased as: Do massive stars form similarly to low-mass stars, but with enhanced accretion rates, or are different processes taking place, e.g., the coalescence and merging of intermediate-mass protostars in the very center of star-forming clusters? This thesis investigates the earliest known stages of massive star formation and studies many characteristic parameters to set constraints on the associated physical processes. The analysis and results of my work strongly support the accretion hypothesis and may be summarized as follows: Massive stars can form via accretion processes that are qualitatively similar and quantitatively enhanced compared to the low-mass case. Coalescence of protostars may occur in some sources, but our data indicate that merging of protostars is not the dominating process for high-mass star formation. Because the inner few AU of a star-forming cluster, where the accretion and/or coalescence processes take place, are difficult to resolve with current observational techniques at typical source distances of several kpc, indirect evidence has to be found to answer the initial question. A sample of 69 high-mass protostellar candidates was selected and studied first statistically from the cm and mm regime to near-infrared wavelengths. The analysis revealed that the chosen sample selection criteria very effectively selected a large number of luminous and massive sources at very early evolutionary stages prior to forming a significant ultracompact HII region. Most likely, these sources produce a large fraction of their luminosity by accretion. A detailed analysis of the intensity and density distributions of the sample from 1.2 mm dust continuum emission maps with 11'' spatial resolution shows that the single-dish radial profiles are not well fitted by single power-law distributions, but that they steepen towards the outside and flatten towards the center. While we interpret the steepening to the outside as a signature of the finite sizes of the star-forming cores, the inner flattening indicates fragmentation of the massive cores into a number of sub-sources. The latter is also observed in high-resolution interferometric data of some of the regions. Additionally, the inner power-law density distributions do not show strong deviations from density distributions of low-mass star-forming cores, which indicates that the initial conditions of low- and high-mass star formation are not very different. As massive molecular outflows on large scales provide insights into the star formation process at the center of the regions, we mapped the outflows of a sub-sample in the CO(2-1) line. The data, observed at higher spatial resolution (11'') than previous studies, reveal that massive bipolar and collimated outflows are as ubiquitous phenomena in high-mass star-forming regions as is also true for their low-mass counterparts. Such collimated outflows are most likely produced by star--disk interactions, and hence, massive stars should have disks as well. The observations presented in this thesis reveal accretion rate estimates in the high-mass regime around 10^-4 Msun/yr, rising as high as 10-3 Msun/yr. Such accretion rates should be sufficiently high to overcome the radiative pressure of the central protostar, and accretion can continue to form massive stars. Additionally, we find that the accretion rate of the most massive object in a core scales roughly linearly with the core mass. Furthermore, a high-resolution interferometric case study of one of our sample sources shows that its outflow, which was already known from single-dish observations, actually splits up into at least three bipolar outflows. One of this outflows is the most collimated massive outflow ever observed in molecular gas. These results give strong support to the hypothesis that massive stars form in analogous fashion to low-mass stars; they merely differ in having higher accretion rates, core masses, luminosities and outflow masses. A study of CH3OH a

Beuther, H.

2002-03-01

109

Methods and Agents for Enhancing Bone Formation or Preventing Bone Loss.  

National Technical Information Service (NTIS)

The present invention provides methods for (i) reducing loss of bone mass or bone density, (ii) increasing bone mass or bone density, (iii) maintaining bone mass or bone density, and/or (iv) reducing loss of calcium from bone, comprising: administering to...

G. R. Crabtree M. M. Winslow

2004-01-01

110

Piezoelectricity could predict sites of formation/resorption in bone remodelling and modelling.  

PubMed

We have developed a mathematical approach for modelling the piezoelectric behaviour of bone tissue in order to evaluate the electrical surface charges in bone under different mechanical conditions. This model is able to explain how bones change their curvature, where osteoblasts or osteoclasts could detect in the periosteal/endosteal surfaces the different electrical charges promoting bone formation or resorption. This mechanism also allows to understand the BMU progression in function of the electro-mechanical bone behaviour. PMID:22001080

Fernández, J R; García-Aznar, J M; Martínez, R

2011-10-08

111

Long-term evaluation of recombinant human bone morphogenetic protein-2 induced bone formation with a biologic and synthetic delivery system.  

PubMed

The efficacy of microspheres made of polylactic acid polyglycolic acid copolymer mixed with blood clot as a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2) was evaluated and the long term behaviour of rhBMP-2 in rats was studied. Twenty micro grams of rhBMP-2 in 200 microliter carrier (blood coagulum and polylactic acid polyglycolic acid porous microspheres) were implanted subcutaneously over both sides of the chest muscles in 40 5-week-old male Long Evans rats. The control group were implanted with carrier alone. Specimens were retrieved after 3 days and weekly for 9 weeks. Outcome was measured by signs of bone formation on low power radiographs, and signs of bony growth on histological examination. There were no signs of foreign body or inflammatory reactions to the carrier in either group. In the experimental group signs of bone formation had started to appear by the end of the first week, and there was a gradual increase in both radio-opacity and size during the observation period. Histologically the bony growth was beginning to mature by 4 weeks and was fully mature by 7-9 weeks. In contrast there was no sign of cartilage or bone formation in the control group and the carrier had resorbed by 4-6 weeks. It is concluded that rhBMP-2 implanted in a carrier consisting of blood clot and porous microspheres made of polylactic acid polyglycolic acid induces rapid proliferation of mesenchymal cells that lead to formation of cartilage and bone by 7 days which had matured by 9 weeks. rhBMP-2 in this carrier may be useful clinically because of its capacity to induce early formation of bone. PMID:8909733

Alpaslan, C; Irie, K; Takahashi, K; Ohashi, N; Sakai, H; Nakajima, T; Ozawa, H

1996-10-01

112

Longitudinal in vivo imaging of bone formation and resorption using fluorescence molecular tomography.  

PubMed

Bone research often focuses on anatomical imaging of the bone microstructure, but in order to gain better understanding in how bone remodeling is modulated through interventions also bone formation and resorption processes should be investigated. With this in mind, the purpose of this study was to establish a longitudinal in vivo imaging approach of bone formation and resorption using fluorescence molecular tomography (FMT). In this study the reproducibility, accuracy and sensitivity of FMT for bone imaging were assessed by performing longitudinal measurements with FMT and comparing it to in vivo micro-computed tomography on a set of control mice, and mice in which load-adaptation was induced in the sixth caudal vertebra. The precision error for FMT measurements, expressed as coefficient of variation, was smaller than 16%, indicating acceptable reproducibility. A correlation was found between bone resorption measured with FMT and bone resorption rate measured with in vivo micro-computed tomography only over the first 14days (R=0.81, p<0.01), but not between bone formation measured with FMT and bone formation rate measured with in vivo micro-CT. Bone formation measured by FMT was 89-109% greater (p<0.05) for mice subjected to mechanical loading than control mice. Bone resorption was 5-8% lower, but did not reach a significant difference between groups, indicating moderate sensitivity for FMT. In conclusion, in vivo FMT in mouse tail bones is feasible but needs to be optimized for monitoring load adaptation in living mice. PMID:23142804

Lambers, F M; Stuker, F; Weigt, C; Kuhn, G; Koch, K; Schulte, F A; Ripoll, J; Rudin, M; Müller, R

2012-11-08

113

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

USGS Publications Warehouse

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

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

2003-01-01

114

Dual Delivery of rhPDGF-BB and Bone Marrow Mesenchymal Stromal Cells Expressing the BMP2 Gene Enhance Bone Formation in a Critical-Sized Defect Model.  

PubMed

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis. PMID:23901900

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

2013-07-31

115

The relationship between inflammation and new bone formation in patients with ankylosing spondylitis  

Microsoft Academic Search

INTRODUCTION: Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. METHODS: Spinal magnetic resonance images and conventional

Xenofon Baraliakos; Joachim Listing; Martin Rudwaleit; Joachim Sieper; Juergen Braun

2008-01-01

116

PRP modulates expression of bone matrix proteins in vivo without long-term effects on bone formation  

Microsoft Academic Search

This experimental study (domestic pig) examined the bone formation after filling defined defects of the frontal skull with autogenous bone or a deproteinized bovine bone matrix (DBBM) in combination with platelet-rich plasma (PRP). Six groups, both materials with and without PRP in two different concentrations (4.1× and 6.5× referring to untreated whole blood) were evaluated at 2, 4, 12, and

Michael Thorwarth; Falk Wehrhan; Stefan Schultze-Mosgau; Jörg Wiltfang; Karl Andreas Schlegel

2006-01-01

117

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

PubMed

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

2013-01-05

118

Nanoscale control of silica particle formation via silk-silica fusion proteins for bone regeneration.  

PubMed

The biomimetic design of silk/silica fusion proteins was carried out, combining the self assembling domains of spider dragline silk (Nephila clavipes) and silaffin derived R5 peptide of Cylindrotheca fusiformis that is responsible for silica mineralization. Genetic engineering was used to generate the protein-based biomaterials incorporating the physical properties of both components. With genetic control over the nanodomain sizes and chemistry, as well as modification of synthetic conditions for silica formation, controlled mineralized silk films with different silica morphologies and distributions were successfully generated; generating 3D porous networks, clustered silica nanoparticles (SNPs), or single SNPs. Silk serves as the organic scaffolding to control the material stability and multiprocessing makes silk/silica biomaterials suitable for different tissue regenerative applications. The influence of these new silk-silica composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on the silk/silica films. The presence of the silica in the silk films influenced osteogenic gene expression, with the upregulation of alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col 1) markers. Evidence for early bone formation as calcium deposits was observed on silk films with silica. These results indicate the potential utility of these new silk/silica systems towards bone regeneration. PMID:20976116

Mieszawska, Aneta J; Nadkarni, Lauren D; Perry, Carole C; Kaplan, David L

2010-10-26

119

Nanoscale control of silica particle formation via silk-silica fusion proteins for bone regeneration  

PubMed Central

The biomimetic design of silk/silica fusion proteins was carried out, combining the self assembling domains of spider dragline silk (Nephila clavipes) and silaffin derived R5 peptide of Cylindrotheca fusiformis that is responsible for silica mineralization. Genetic engineering was used to generate the protein-based biomaterials incorporating the physical properties of both components. With genetic control over the nanodomain sizes and chemistry, as well as modification of synthetic conditions for silica formation, controlled mineralized silk films with different silica morphologies and distributions were successfully generated; generating 3D porous networks, clustered silica nanoparticles (SNPs), or single SNPs. Silk serves as the organic scaffolding to control the material stability and multiprocessing makes silk/silica biomaterials suitable for different tissue regenerative applications. The influence of these new silk-silica composite systems on osteogenesis was evaluated with human mesenchymal stem cells (hMSCs) subjected to osteogenic differentiation. hMSCs adhered, proliferated, and differentiated towards osteogenic lineages on the silk/silica films. The presence of the silica in the silk films influenced osteogenic gene expression, with the upregulation of alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col 1) markers. Evidence for early bone formation as calcium deposits was observed on silk films with silica. These results indicate the potential utility of these new silk/silica systems towards bone regeneration.

Mieszawska, Aneta J.; Nadkarni, Lauren D.; Perry, Carole C.

2010-01-01

120

Lower circulating preptin levels in male patients with osteoporosis are correlated with bone mineral density and bone formation  

PubMed Central

Background Serum preptin levels among subjects with different bone mineral densities (BMD) were measured and investigated to determine the correlation between BMD and bone-metabolic markers. Methods Approximately 52 elderly male patients with osteoporosis, 50 elderly men with osteopaenia, and 31 age-matched normal bone mass controls participated in the study. The serum preptin levels and bone metabolic markers were measured by enzyme-linked immunosorbent assay. The relationships between preptin levels, BMD, and metabolic parameters were also assessed. Results The serum preptin level was the lowest in the osteoporosis group and positively correlated with BMD. All the bone formation markers in the osteoporosis and osteopaenia groups were significantly reduced compared with those in the normal group. Serum preptin level was positively correlated with all the bone formation markers, whereas no correlation was observed with the bone resorption marker TRACP-5b. Conclusions Serum preptin levels are decreased in osteoporosis and osteopaenia patients and positively correlated with BMD. Therefore, preptin is involved in the pathogenesis of osteoporosis, probably through bone formation rather than bone resorption.

2013-01-01

121

Rat bone marrow stromal cell-conditioned medium promotes early osseointegration of titanium implants.  

PubMed

Purpose: To enhance the stability of titanium (Ti) implants using conditioned medium (CM) derived from rat bone marrow stromal cell (BMSC). Materials and Methods: BMSCs were isolated from rat femurs and grown in culture, and the culture medium was used as CM. The CM was immobilized on the surface of Ti implants with calcifying solution. The topology of the Ti implants after immobilization of CM was observed by scanning electron microscopy (SEM). The Ti-immobilized CM was analyzed by liquid chromatography with tandem mass spectrometry. The adhesiveness and the osteogenic differentiation of BMSCs grown on CM-coated discs were analyzed by reverse-transcription polymerase chain reaction. Ti implants with specimen-immobilized CM labeled with quantum dots (QDs) were placed into rat femurs. The localization of the CM was detected by in vivo imaging at 1, 7, 14, and 28 days after implantation. The removal torque test and histologic bone implant contact (BIC) were also analyzed. Results: Rat BMSC-CM was successfully immobilized on Ti implants. The immobilized CM contained about 2000 proteins, including collagen type I, bone sialoprotein, fibronectin, and vascular endothelial growth factor that are important in new bone formation. CM promoted cell adhesion and osteocalcin gene expression of rat BMSCs. The labeled CM remained associated with the Ti implant at 1, 7, 14, and 28 days postimplantation. The removal torque value and BIC of Ti implants with immobilized CM were higher than those of control implants on days 1, 7, and 14 after implantation. Conclusion: Immobilized CM components on the surface of Ti implants promoted integration into bone during an early stage. PMID:24066329

Tsuchiya, Shuhei; Hara, Kenji; Ikeno, Masayuki; Okamoto, Yasuhiro; Hibi, Hideharu; Ueda, Minoru

122

Fresh-frozen human bone allograft in vertical ridge augmentation: clinical and tomographic evaluation of bone formation and resorption.  

PubMed

The aim of the current study is to evaluate fresh-frozen human bone allografts (FHBAs) used in vertical ridge augmentation clinically and by computed tomography, and to analyze the resulting bone formation and graft resorption. Sixteen FHBAs were grafted in the maxillae and mandibles of 9 patients. The FHBAs, which were provided by the Musculoskeletal Tissue Bank of Marilia Hospital (Unioss), were frozen at -80°C. After 7 months, dental implants were placed and bone parameters were evaluated. Vertical bone formation was measured by computerized tomography before (T0) and at 7 months (T1) after the surgical procedure. Bone graft resorption was measured clinically from a landmark screw head using a periodontal probe. The results were analyzed by Student's t-test. Significant differences existed in the bone formation values at T0 and T1, with an average change of 4.03 ± 1.69 mm. Bone graft resorption values were 1.0 ± 0.82 mm (20%). Implants were placed with varying insertion torque values (35-45 Ncm), and achieved primary stability. This study demonstrates that FHBAs promote satisfactory vertical bone formation with a low resorption rates, good density, and primary implant stability. PMID:21811779

Macedo, Luis Guilherme Scavone; Mazzucchelli-Cosmo, Luiz Antonio; Macedo, Nelson Luiz; Monteiro, Adriana Socorro Ferreira; Sendyk, Wilson Roberto

2011-08-03

123

Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration.  

PubMed

During endochondral bone development, bone-forming osteoblasts have to colonize the regions of cartilage that will be replaced by bone. In adulthood, bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, as a prerequisite for skeletal health. A failure of osteoblasts to reach the sites in need of bone formation may contribute to impaired fracture repair. Conversely, stimulation of osteogenic cell recruitment may be a promising osteo-anabolic strategy to improve bone formation in low bone mass disorders such as osteoporosis and in bone regeneration applications. Yet, still relatively little is known about the cellular and molecular mechanisms controlling osteogenic cell recruitment to sites of bone formation. In vitro, several secreted growth factors have been shown to induce osteogenic cell migration. Recent studies have started to shed light on the role of such chemotactic signals in the regulation of osteoblast recruitment during bone remodeling. Moreover, trafficking of osteogenic cells during endochondral bone development and repair was visualized in vivo by lineage tracing, revealing that the capacity of osteoblast lineage cells to move into new bone centers is largely confined to undifferentiated osteoprogenitors, and coupled to angiogenic invasion of the bone-modeling cartilage intermediate. It is well known that the presence of blood vessels is absolutely required for bone formation, and that a close spatial and temporal relationship exists between osteogenesis and angiogenesis. Studies using genetically modified mouse models have identified some of the molecular constituents of this osteogenic-angiogenic coupling. This article reviews the current knowledge on the process of osteoblast lineage cell recruitment to sites of active bone formation in skeletal development, remodeling, and repair, considering the role of chemo-attractants for osteogenic cells and the interplay between osteogenesis and angiogenesis in the control of bone formation. Birth Defects Research (Part C) 99:170-191, 2013. © 2013 Wiley Periodicals, Inc. PMID:24078495

Dirckx, Naomi; Van Hul, Matthias; Maes, Christa

2013-09-01

124

Bone Formation and Resorption Are Both Increased in Experimental Autoimmune Arthritis  

PubMed Central

Introduction Arthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation. This process is not completely understood, and especially the importance of local inflammation needs further investigation. We evaluated how bone formation and bone resorption are altered in experimental autoimmune arthritis. Methods Twenty-one female SKG mice were randomized to either an arthritis group or a control group. Tetracycline was used to identify mineralizing surfaces. After six weeks the right hind paws were embedded undecalcified in methylmethacrylate. The paws were cut exhaustively according to the principles of vertical sectioning and systematic sampling. 3D design-based methods were used to estimate the total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast-covered bone surfaces. In addition the presence of adjacent inflammation was ascertained. Results The total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast covered surfaces were elevated in arthritic paws compared to normal paws. Mineralizing surfaces were elevated adjacent to as well as not adjacent to inflammation in arthritic mice compared to normal mice. In arthritic mice, eroded surfaces and osteoclast covered surfaces were larger on bone surfaces adjacent to inflammation than on bone surfaces without adjacent inflammation. However, we found no difference between mineralizing surfaces at bone surfaces with or without inflammation in arthritic mice. Conclusions Inflammation induced an increase in resorptive bone surfaces as well as formative bone surfaces. The bone formative response may be more general, since formative bone surfaces were also increased when not associated with inflammation. Thus, the bone loss may be the result of a substantial local bone resorption, which cannot be compensated by the increased local bone formation. These findings may be valuable for the development of new osteoblast targeting drugs in RA.

Keller, Kresten Krarup; Thomsen, Jesper Skovhus; Stengaard-Pedersen, Kristian; Dagnaes-Hansen, Frederik; Nyengaard, Jens Randel; Hauge, Ellen-Margrethe

2012-01-01

125

New bone formation in nude mouse calvaria induced by canine prostate tissue.  

PubMed

Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites also may lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor-cell osteo-induction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue. Collagenase-digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post-implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate-resistant acid phosphatase staining for osteoclasts. The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate-implanted calvaria significantly increased (1.7-fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically-induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue. In conclusion, this animal model will be useful for investigating the roles of prostate-derived growth factors on new bone formation in vivo. PMID:12431820

LeRoy, Bruce E; Bahnson, Robert R; Rosol, Thomas J

2002-11-29

126

Ceremonialism in the Early Formative of Ecuador  

Microsoft Academic Search

munity early in my career, but it has taken me more than two decades to com- prehend some of the lessons and understand their implications for archaeological research. Like many other archaeologists I have tended to separate archaeological data into ceremonial and nonceremonial categories. Yet, among South American indigenous societies there was probably no sharp boundary, either conceptually or' behaviorally,

SENRI ETHNOLOGICAIL; J. SCoTT RAYMOND

1993-01-01

127

Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans  

PubMed Central

Bone- and cartilage-derived morphogenetic proteins (BMPs and CDMPs), which are TGF? superfamily members, are growth and differentiation factors that have been recently isolated, cloned and biologically characterized. They are important regulators of key events in the processes of bone formation during embryogenesis, postnatal growth, remodelling and regeneration of the skeleton. In the present study, we used immunohistochemical methods to investigate the distribution of BMP-2, -3, -5, -6, -7 and CDMP-1, -2, -3 in human osteophytes (abnormal bony outgrowths) isolated from osteoarthritic hip and knee joints from patients undergoing total joint replacement surgery. All osteophytes consisted of three different areas of active bone formation: (1) endochondral bone formation within cartilage residues; (2) intramembranous bone formation within the fibrous tissue cover and (3) bone formation within bone marrow spaces. The immunohistochemistry of certain BMPs and CDMPs in each of these three different bone formation sites was determined. The results indicate that each BMP has a distinct pattern of distribution. Immunoreactivity for BMP-2 was observed in fibrous tissue matrix as well as in osteoblasts; BMP-3 was mainly present in osteoblasts; BMP-6 was restricted to young osteocytes and bone matrix; BMP-7 was observed in hypertrophic chondrocytes, osteoblasts and young osteocytes of both endochondral and intramembranous bone formation sites. CDMP-1, -2 and -3 were strongly expressed in all cartilage cells. Surprisingly, BMP-3 and -6 were found in osteoclasts at the sites of bone resorption. Since a similar distribution pattern of bone morphogenetic proteins was observed during embryonal bone development, it is suggested that osteophyte formation is regulated by the same molecular mechanism as normal bone during embryogenesis.

Zoricic, Sanja; Maric, Ivana; Bobinac, Dragica; Vukicevic, Slobodan

2003-01-01

128

Osteocyte control of bone formation via sclerostin, a novel BMP antagonist  

PubMed Central

There is an unmet medical need for anabolic treatments to restore lost bone. Human genetic bone disorders provide insight into bone regulatory processes. Sclerosteosis is a disease typified by high bone mass due to the loss of SOST expression. Sclerostin, the SOST gene protein product, competed with the type I and type II bone morphogenetic protein (BMP) receptors for binding to BMPs, decreased BMP signaling and suppressed mineralization of osteoblastic cells. SOST expression was detected in cultured osteoblasts and in mineralizing areas of the skeleton, but not in osteoclasts. Strong expression in osteocytes suggested that sclerostin expressed by these central regulatory cells mediates bone homeostasis. Transgenic mice overexpressing SOST exhibited low bone mass and decreased bone strength as the result of a significant reduction in osteoblast activity and subsequently, bone formation. Modulation of this osteocyte-derived negative signal is therapeutically relevant for disorders associated with bone loss.

Winkler, David G.; Sutherland, May Kung; Geoghegan, James C.; Yu, Changpu; Hayes, Trenton; Skonier, John E.; Shpektor, Diana; Jonas, Mechtild; Kovacevich, Brian R.; Staehling-Hampton, Karen; Appleby, Mark; Brunkow, Mary E.; Latham, John A.

2003-01-01

129

Early Union Formation in Canada: Links with Education  

Microsoft Academic Search

This article examines the link between early union formation and education using a new Canadian longitudinal data set, the\\u000a Youth in Transition Survey (YITS). Educational transitions and early union formation occur around the same time in young adulthood,\\u000a yet the roles of student and conjugal partner are often thought to be incompatible. We examine the effect of two important\\u000a educational

Darcy W. Hango; Céline Le Bourdais

2007-01-01

130

Bone nodules on chitosan–polygalacturonic acid–hydroxyapatite nanocomposite films mimic hierarchy of natural bone  

Microsoft Academic Search

The ultimate goal of bone tissue engineering is to develop bony tissues on tissue engineered constructs that mimic the native bone. Nanoscale characterization of in vitro generated bony tissues on engineered scaffolds is essential to understanding both the physical and mechanical characteristics of the engineered bone. Bone nodule formation, a typical early indicator of bone formation was observed on chitosan–polygalacturonic

Rohit Khanna; Kalpana S. Katti; Dinesh R. Katti

2011-01-01

131

Wnt signaling in bone formation and its therapeutic potential for bone diseases  

PubMed Central

The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3?, has also been reported to stimulate osteogenesis by stabilizing ? catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential.

Kim, Jeong Hwan; Liu, Xing; Wang, Jinhua; Chen, Xiang; Zhang, Hongyu; Kim, Stephanie H.; Cui, Jing; Li, Ruidong; Zhang, Wenwen; Kong, Yuhan; Zhang, Jiye; Shui, Wei; Lamplot, Joseph; Rogers, Mary Rose; Zhao, Chen; Wang, Ning; Rajan, Prashant; Tomal, Justin; Statz, Joseph; Wu, Ningning; Luu, Hue H.; Haydon, Rex C.

2013-01-01

132

Wnt signaling in bone formation and its therapeutic potential for bone diseases.  

PubMed

The Wnt signaling pathway plays an important role not only in embryonic development but also in the maintenance and differentiation of the stem cells in adulthood. In particular, Wnt signaling has been shown as an important regulatory pathway in the osteogenic differentiation of mesenchymal stem cells. Induction of the Wnt signaling pathway promotes bone formation while inactivation of the pathway leads to osteopenic states. Our current understanding of Wnt signaling in osteogenesis elucidates the molecular mechanisms of classic osteogenic pathologies. Activating and inactivating aberrations of the canonical Wnt signaling pathway in osteogenesis results in sclerosteosis and osteoporosis respectively. Recent studies have sought to target the Wnt signaling pathway to treat osteogenic disorders. Potential therapeutic approaches attempt to stimulate the Wnt signaling pathway by upregulating the intracellular mediators of the Wnt signaling cascade and inhibiting the endogenous antagonists of the pathway. Antibodies against endogenous antagonists, such as sclerostin and dickkopf-1, have demonstrated promising results in promoting bone formation and fracture healing. Lithium, an inhibitor of glycogen synthase kinase 3?, has also been reported to stimulate osteogenesis by stabilizing ? catenin. Although manipulating the Wnt signaling pathway has abundant therapeutic potential, it requires cautious approach due to risks of tumorigenesis. The present review discusses the role of the Wnt signaling pathway in osteogenesis and examines its targeted therapeutic potential. PMID:23514963

Kim, Jeong Hwan; Liu, Xing; Wang, Jinhua; Chen, Xiang; Zhang, Hongyu; Kim, Stephanie H; Cui, Jing; Li, Ruidong; Zhang, Wenwen; Kong, Yuhan; Zhang, Jiye; Shui, Wei; Lamplot, Joseph; Rogers, Mary Rose; Zhao, Chen; Wang, Ning; Rajan, Prashant; Tomal, Justin; Statz, Joseph; Wu, Ningning; Luu, Hue H; Haydon, Rex C; He, Tong-Chuan

2013-02-01

133

Electrical Stimulation Enhances Cellular/Molecular Functions of Osteoblasts Relevant to New Bone Formation in Vitro.  

National Technical Information Service (NTIS)

The static conditions conventionally used in tissue-culture do not represent the biophysical milieu of bone in vivo and, thus, leave cells without stimuli which may affect functions pertinent to new bone formation. Bone in vivo exists in a dynamic environ...

P. R. Supronowicz K. R. Ullmann P. M. Ajayan B. P. Arulanandam D. W. Metzger

2001-01-01

134

Stratigraphy and depositional history, Bone Spring Formation, Lea County, New Mexico  

Microsoft Academic Search

The Bone Spring formation of the northern Delaware basin in southeastern New Mexico produces oil in Lea County from foreshelf detrital carbonate facies, such as in Scharb field. Production there comes from several intervals. Stratigraphic correlations between the various Bone Springs units and equivalent Leonardian facies of the Northwest shelf in Lea County suggest that the Bone Spring is correlative

Mazzullo

1987-01-01

135

Zinc-containing tricalcium phosphate and related materials for promoting bone formation  

Microsoft Academic Search

Calcium phosphate is a suitable carrier of zinc, an essential element that has stimulatory effects on bone formation in vitro and in vivo as well as an inhibitory effect on osteoclastic bone resorption in vitro. The highest zinc content is attained in ?-tricalcium phosphate, where the zinc content reaches 6wt%. Both rat and human bone marrow cells (BMCs) cultured on

Atsuo Ito; Makoto Otsuka; Haruo Kawamura; Masako Ikeuchi; Hajime Ohgushi; Y. Sogo; Noboru Ichinose

2005-01-01

136

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

PubMed

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. PMID:24077482

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

2013-09-27

137

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

138

Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum.  

PubMed

Loss- and gain-of-function mutations in the broadly expressed gene Lrp5 affect bone formation, causing osteoporosis and high bone mass, respectively. Although Lrp5 is viewed as a Wnt coreceptor, osteoblast-specific disruption of beta-Catenin does not affect bone formation. Instead, we show here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum. Accordingly, decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and gut- but not osteoblast-specific Lrp5 inactivation decreases bone formation in a beta-Catenin-independent manner. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents ovariectomy-induced bone loss. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass. PMID:19041748

Yadav, Vijay K; Ryu, Je-Hwang; Suda, Nina; Tanaka, Kenji F; Gingrich, Jay A; Schütz, Günther; Glorieux, Francis H; Chiang, Cherie Y; Zajac, Jeffrey D; Insogna, Karl L; Mann, J John; Hen, Rene; Ducy, Patricia; Karsenty, Gerard

2008-11-28

139

MRI detection of early bone metastases in B16 mouse melanoma models  

PubMed Central

Bone metastasis causes significant morbidity in cancer patients, including bone pain, pathologic fractures, nerve compression syndrome, and hypercalcemia. Animal models are utilized to study the pathogenesis of skeletal metastases and to evaluate potential therapeutic agents. Previously published methods for imaging bone metastasis in rodent models have focused on identifying advanced stage metastasis using simple X-rays. Here we report MRI as a method for detecting early bone metastases in mouse models in vivo. B16 mouse melanoma cells were injected into the left cardiac ventricle of C57BL/6 mice and magnetic resonance (MR) images were obtained of the left leg following the development of metastatic disease, when tumor associated bone destruction was histologically present but not visible by X-ray. T1 and T2 relaxation times of bone marrow were measured in healthy control mice and B16 melanoma tumor-bearing mice. Mean T2 values for normal marrow were 28 ms (SD 5) and for diseased bone marrow were 41 ms (SD 3). T2 relaxation time of diseased bone marrow is significantly longer than that of normal bone marrow (P < 0.0001) and can be used as a marker of early bone metastases. These studies demonstrate that MR imaging can detect bone marrow metastases in small animals prior to development of cortical bone loss identified by X-ray.

Gauvain, Karen M.; Garbow, Joel R.; Song, Sheng-Kwei; Hirbe, Angela C.; Weilbaecher, Katherine

2009-01-01

140

Mesenchymal Stem Cells Expressing Osteogenic and Angiogenic Factors Synergistically Enhance Bone Formation in a Mouse Model of Segmental Bone Defect  

PubMed Central

The potential of mesenchymal stem cells (MSC) in tissue regeneration is increasingly gaining attention. There is now accumulating evidence that MSC make an important contribution to postnatal vasculogenesis. During bone development and fracture healing, vascularization is observed before bone formation. The present study determined the potential of MSC, transduced ex vivo with a recombinant adeno-associated virus 6 (rAAV6) encoding bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) in a mouse model of segmental bone defect created in the tibiae of athymic nude mice. Mouse MSC that were mock-transduced or transduced with rAAV6-BMP2:VEGF were systemically transplanted following radiographic confirmation of the osteotomy. Effects of the therapy were determined by enzyme-linked immunosorbent assay measurements for BMP2 and VEGF, dual-energy X-ray absorptiometry (DXA) for bone density, three-dimensional microcomputed tomography (µCT) for bone and capillary architecture, and histomorphometry for bone remodeling. Results of these analyses indicated enhanced bone formation in the group that received BMP2+VEGF-expressing MSC compared to other groups. The therapeutic effects were accompanied by increased vascularity and osteoblastogenesis, indicating its potential for effective use while treating difficult nonunion bone defects in humans.

Kumar, Sanjay; Wan, Chao; Ramaswamy, Girish; Clemens, Thomas L; Ponnazhagan, Selvarangan

2010-01-01

141

Bone morphogenetic protein-induced inflammatory cyst formation after lumbar fusion causing nerve root compression.  

PubMed

Bone morphogenetic protein (BMP) has been reported to cause early inflammatory changes, ectopic bony formation, adjacent level fusion, radiculitis, and osteolysis. The authors describe the case of a patient who developed inflammatory fibroblastic cyst formation around the BMP sponge after a lumbar fusion, resulting in compressive lumbar radiculopathy. A 70-year-old woman presented with left L-4 and L-5 radiculopathy caused by a Grade I spondylolisthesis with a left herniated disc at L4-5. She underwent a minimally invasive transforaminal lumbar interbody fusion with BMP packed into the interbody cage at L4-5. Her neurological symptoms resolved immediately postoperatively. Six weeks later, the patient developed recurrence of radiculopathy. Radiological imaging demonstrated an intraspinal cyst with a fluid-fluid level causing compression of the left L-4 and L-5 nerve roots. Reexpoloration of the fusion was performed, and a cyst arising from the posterior aspect of the cage was found to compress the axilla of the left L-4 nerve root and the shoulder of the L-5 nerve root. The cyst was decompressed, and the wall was partially excised. A collagen BMP sponge was found within the cyst and was removed. Postoperatively, the patient's radiculopathy resolved and she went on to achieve interbody fusion. Bone morphogenetic protein can be associated with inflammatory cyst formation resulting in neural compression. Spine surgeons should be aware of this complication in addition to the other reported BMP-related complications. PMID:22176433

Choudhry, Osamah J; Christiano, Lana D; Singh, Rahul; Golden, Barbara M; Liu, James K

2011-12-16

142

Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor.  

PubMed

Sirt1, the mammalian ortholog of the yeast Sir2 (silent information regulator 2), was shown to play an important role in metabolism and in age-associated diseases, but its role in skeletal homeostasis and osteoporosis has yet not been studied. Using 129/Sv mice with a germline mutation in the Sirt1 gene, we demonstrate that Sirt1 haplo-insufficient (Sirt1(+/-)) female mice exhibit a significant reduction in bone mass characterized by decreased bone formation and increased marrow adipogenesis. Importantly, we identify Sost, encoding for sclerostin, a critical inhibitor of bone formation, as a novel target of Sirt1. Using chromatin immunoprecipitation analysis, we reveal that Sirt1 directly and negatively regulates Sost gene expression by deacetylating histone 3 at lysine 9 at the Sost promoter. Sost down-regulation by small interfering RNA and the administration of a sclerostin-neutralizing antibody restore gene expression of osteocalcin and bone sialoprotein as well as mineralized nodule formation in Sirt1(+/-) marrow-derived mesenchymal stem cells induced to osteogenesis. These findings reveal a novel role for Sirt1 in bone as a regulator of bone mass and a repressor of sclerostin, and have potential implications suggesting that Sirt1 is a target for promoting bone formation as an anabolic approach for treatment of osteoporosis. PMID:21952235

Cohen-Kfir, Einav; Artsi, Hanna; Levin, Avi; Abramowitz, Eva; Bajayo, Alon; Gurt, Irina; Zhong, Lei; D'Urso, Agustina; Toiber, Debra; Mostoslavsky, Raul; Dresner-Pollak, Rivka

2011-09-27

143

[Requirements for early discharge after allogeneic bone marrow transplantation].  

PubMed

To assess the requirements for early discharge after allogeneic bone marrow transplantation (BMT), we evaluated infectious complications and transplantation-related toxicity (TRT) among 46 recipients who underwent allogeneic BMT between January 1997 and August 1999 at our institute. Acute graft-versus-host disease (GVHD) and cytomegalovirus (CMV) antigenemia developed in 29 and 26 patients, respectively. More than 95% of the episodes occurred before day 70. Among the patients without CMV antigenemia and without prednisolone (PSL) therapy for acute GVHD (n = 15), only 3 developed TRT or infections (pneumonia, varicella zoster virus infection and hemolytic uremic syndrome), but all of these episodes were cured without fatality. On the other hand, in patients with CMV antigenemia and/or PSL therapy for acute GVHD, a high incidence of TRT and infectious complications was observed until day 180, and some of these episodes were fatal. In conclusion, discharge on day 70 after allogeneic BMT seems to be safe for patients who do not develop CMV antigenemia or receive PSL therapy for acute GVHD. PMID:11579498

Yasumi, M; Karasuno, T; Kanashima, H; Masaie, H; Taniguchi, H; Mitsui, H; Nakamura, H; Hiraoka, A

2001-08-01

144

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.

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

2011-01-01

145

Connexin 43 deficiency attenuates loss of trabecular bone and prevents suppression of cortical bone formation during unloading.  

PubMed

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 3 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. After 3 weeks of HLS, wild-type (WT) mice experienced a substantial decline 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 after unloading of WT mice. This suppression of bone formation was not observed in cKO mice, in which 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

2012-11-01

146

Lanthanum salts improve bone formation in a small animal model of post-menopausal osteoporosis.  

PubMed

Two different lanthanum salts, lanthanum carbonate (LaCO(3)) and Lancer(®), a lanthanide citrate mixture, were tested for their effects on bone metabolism in a small animal model for post-menopausal osteoporosis. Forty female outbred Wistar Han rats, sham-operated (SHAM, positive control, n = 10) or ovariectomized (OVX, n = 30) at 4 months of age, were allotted into following groups (n = 10/group): (i) SHAM, (ii) OVX control (negative control), (iii) OVX + LaCO(3) (1.74 g/kg feed) and (iv) OVX + Lancer(®) (8 g/kg feed). Effects on bone were investigated by bone markers [osteocalcin (Oc) in serum and excretion of pyridinoline (PYD) in urine] and by physical parameters of bone structure and bone composition (bone mass, calcium, phosphorus and magnesium content in bone crude ash). Bone micro-architecture and bone mineral density were evaluated by peripheral quantitative computed tomography and micro-computed tomography (?CT). The animal model could be validated by differences between OVX control and SHAM. Body mass and feed intake were the same among the four groups. Oc was clearly increased in the two experimental groups (p < 0.001) vs. SHAM and OVX control. Bone mass and calcium content in bone ash were significantly higher than in OVX control. The Ca/P ratio in bone ash of the two lanthanide groups did not differ from SHAM. Bone-protecting effects of lanthanides were clearly demonstrated by an increased trabecular density which is the region of interest for osteoporotic bone loss. A 3D imaging of bone micro-architecture by ?CT visualized descriptively the positive effects of lanthanides on bone formation. The results of this study demonstrate an improvement of bone formation and bone-protecting effects of lanthanides in the OVX rat. Thus, lanthanum salts suggest a prevention of post-menopausal bone loss and may be of benefit in experimental osteopenia following ovariectomy. PMID:22845174

von Rosenberg, S J; Wehr, U A

2012-07-30

147

Simvastatin-loaded ?-TCP drug delivery system induces bone formation and prevents rhabdomyolysis in OVX mice.  

PubMed

Bone formation and regeneration is a prolonged process that requires a slow drug release system to assist in the long-term recovery. A drug-delivery system is developed that allows for the controlled release of simvastin, without exhibiting the side effects associated with high concentrations of simvastatin, and is still capable of inducing constant bone formation. PMID:23184712

Chou, Joshua; Ito, Tomoko; Otsuka, Makoto; Ben-Nissan, Besim; Milthorpe, Bruce

2012-11-26

148

The use of bovine screws to promote bone formation using a tibia model in dogs.  

PubMed

The objective of this study was to evaluate the use of a unique resorbable bovine bone screw to stimulate bone formation. Bovine bone screws were inserted in the tibia of beagle dogs. Each animal received 8 screws, divided into groups A (screws + no membranes), B (screws + titanium reinforced membranes), and C (bone defects treated with autogenous bone grafts). Animals were killed at 2, 4, and 6 months. New bone was measured with a periodontal probe and reported an average of 7.4 mm in vertical bone gain for group B, 3.6 mm for group A, and 1.7 mm for group C. Submission to Kruskal-Wallis test showed statistical differences among groups (P < .05). Histologic examination revealed an intimate contact between the newly formed bone and the resorbing bone screws. We conclude that bovine bone screws provide an environment for new bone formation and thus may provide an alternative therapy for enhancing bone formation vertically, including for regenerative procedures as well as before implant therapy. PMID:23058228

Bianchini, Marco Aurélio; Pontual, Marco Antônio B; Bez, Leonardo; Benfatti, César Augusto M; Boabaid, Fernanda; Somerman, Martha J; Magini, Ricardo S

2012-04-10

149

Localized insulin-like growth factor I delivery to enhance new bone formation  

Microsoft Academic Search

Insulin-like growth factor I (IGF I) exerts an important role during skeletal growth and bone formation. Therefore, its localized delivery appears attractive for the treatment of bone defects. To prolong IGF I delivery, we entrapped the protein into biodegradable poly(lactide-co-glycolide) microspheres (PLGA MS) and evaluated the potential of this delivery system for new bone formation in two defect models of

Lorenz Meinel; Evangelos Zoidis; Jürgen Zapf; Paulo Hassa; Michael O Hottiger; Jörg A Auer; Rebecca Schneider; Bruno Gander; Vera Luginbuehl; Regula Bettschart-Wolfisberger; Oscar E Illi; Hans P Merkle; Brigitte von Rechenberg

2003-01-01

150

Dietary patterns, bone resorption and bone mineral density in early post-menopausal Scottish women  

Microsoft Academic Search

Background\\/Objectives:Several nutrients affect bone turnover. Dietary patterns may provide insights into which foods are important and how nutrition affects bone health. The aim of this study was to investigate the associations between dietary patterns, bone turnover and bone mineral density (BMD).Subjects\\/Methods:This cross-sectional study examined 3236 Scottish women age 50–59 years, who were members of the Aberdeen Prospective Osteoporosis Screening Study.

A C Hardcastle; L Aucott; W D Fraser; D M Reid; H M Macdonald

2011-01-01

151

The Formation and Early Evolution of Stars  

NASA Astrophysics Data System (ADS)

The discovery of bright X-ray emission from young low-mass stars in the wake of the launch of the EINSTEINX-ray observatory (see Chap. 2) [66, 67] truly took researchers by surprise. X-rays from Orion had been detected with Uhuru, the first X-ray satellite launched in the early 1970s, but due to the lack of spatial resolving power a connection to young low-mass stars seemed far from likely. At the time, these stars were investigated for their complex emission patterns at long wavelengths. Models for gravitational collapse do not provide many clues about mechanisms for emissions at wavelengths much shorter than a few microns (see Chaps. 4 and 5). High energy emission requires special circumstances and the responsible physical processes are often different from the ones at the origins of the optical and IR emissions. In order to emit at short wavelengths, one either needs very high temperatures or very high magnetic field strengths or some mechanism to produce high-velocity electrons. The previous chapters already demonstrated that gravitational potentials in protostellar systems are by far too small to free enough energy (see Sect. 6.7). Thus the energy has to come from a different pool, which is most likely rotational and magnetic energy inherited from pre-collapse cloud dynamics. Synchrotron radiation from magnetic fields as high as 1011G can be ruled out on the grounds that superdense degenerate matter, as found in neutron stars, is needed to carry such high field densities [840]. Chapters 6 and 8 also showed that magnetic field strengths in protostellar environments do not exceed 1 or a few kG.

Schulz, Norbert S.

152

Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation  

Microsoft Academic Search

BACKGROUND AND AIMS: There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with

Ulrike ME Schulze; Simone Schuler; Dieter Schlamp; Peter Schneider; Claudia Mehler-Wex

2010-01-01

153

Cross-sex pattern of bone mineral density in early onset gender identity disorder  

Microsoft Academic Search

Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment

I. R. Haraldsen; E. Haug; J. Falch; T. Egeland; S. Opjordsmoen

2007-01-01

154

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

155

Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation  

PubMed Central

Longitudinal bone growth results from endochondral ossification, a process that requires proliferation and differentiation of chondrocytes. It has been shown that proper endochondral bone formation is critically dependent on the retinoblastoma family members p107 and p130. However, the precise functional roles played by individual E2F proteins remain poorly understood. Using both constitutive and conditional E2F1 transgenic mice, we show that ubiquitous transgene-driven expression of E2F1 during embryonic development results in a dwarf phenotype and significantly reduced postnatal viability. Overexpression of E2F1 disturbs chondrocyte maturation, resulting in delayed endochondral ossification, which is characterized by reduced hypertrophic zones and disorganized growth plates. Employing the chondrogenic cell line ATDC5, we investigated the effects of enforced E2F expression on the different phases of chondrocyte maturation that are normally required for endochondral ossification. Ectopic E2F1 expression strongly inhibits early- and late-phase differentiation of ATDC5 cells, accompanied by diminished cartilage nodule formation as well as decreased type II collagen, type X collagen, and aggrecan gene expression. In contrast, overexpression of E2F2 or E2F3a results in only a marginal delay of chondrocyte maturation, and increased E2F4 levels have no effect. These data are consistent with the notion that E2F1 is a regulator of chondrocyte differentiation.

Scheijen, Blanca; Bronk, Marieke; van der Meer, Tiffany; Bernards, Rene

2003-01-01

156

Serum levels of tissue inhibitor of metalloproteinase-1 and periarticular bone loss in early rheumatoid arthritis  

Microsoft Academic Search

We investigated the relationship between disease activity, serum biological mediators of joint damage, and periarticular bone\\u000a loss in inflammatory arthritis. Patients with early inflammatory arthritis were recruited from a dedicated early arthritis\\u000a clinic. At the time of recruitment, all had clinical evidence of synovitis. Patients were assessed at baseline and at 1-year\\u000a follow-up. Periarticular and axial bone mineral density (BMD)

Eithne Murphy; Pascale Roux-Lombard; Terence Rooney; Oliver FitzGerald; Jean-Michel Dayer; Barry Bresnihan

2009-01-01

157

Chinese red yeast rice (Monascus purpureus-fermented rice) promotes bone formation  

PubMed Central

Background Statin can induce the gene expression of bone morphogenetic protein-2. Red yeast rice (RYR, Hongqu), i.e. rice fermented with Monascus purpureus, contains a natural form of statin. This study demonstrates the effects of RYR extract on bone formation. Methods Bone defects were created in the parietal bones of two New Zealand white rabbits. In the test animal, two defects were grafted with collagen matrix mixed with RYR extract. In the control animal, two defects were grafted with collagen matrix alone. UMR 106 cell line was used to test RYR extract in vitro. In the control group, cells were cultured for three durations (24 hours, 48 hours and 72 hours) without any intervention. In the RYR group, cells were cultured for the same durations with various concentrations of RYR extract (0.001 g/ml, 0.005 g/ml and 0.01 g/ml). Bicinchoninic acid (BCA) assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and alkaline phosphatase (ALP) assay were performed to measure total protein, mitochondrial activity and bone cell formation respectively. Results The test animal showed more formation of new bone in the defects than the control animal. RYR significantly increased the optical density in the MTT assay and ALP activity in vitro. Conclusion RYR extract stimulated new bone formation in bone defects in vivo and increased bone cell formation in vitro.

Wong, Ricky WK; Rabie, Bakr

2008-01-01

158

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

PubMed

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

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

2013-10-04

159

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

160

Fresh-frozen human bone allograft in vertical ridge augmentation: clinical and tomographic evaluation of bone formation and resorption  

Microsoft Academic Search

The aim of the current study is to evaluate fresh-frozen human bone allografts (FHBAs) used in vertical ridge augmentation\\u000a clinically and by computed tomography, and to analyze the resulting bone formation and graft resorption. Sixteen FHBAs were\\u000a grafted in the maxillae and mandibles of 9 patients. The FHBAs, which were provided by the Musculoskeletal Tissue Bank of\\u000a Marilia Hospital (Unioss),

Luis Guilherme Scavone Macedo; Luiz Antonio Mazzucchelli-Cosmo; Nelson Luiz Macedo; Adriana Socorro Ferreira Monteiro; Wilson Roberto Sendyk

161

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

SciTech Connect

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

Otsuru, Satoru [Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Tamai, Katsuto [Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)]. E-mail: tamai@gts.med.osaka-u.ac.jp; Yamazaki, Takehiko [Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Kaneda, Yasufumi [Division of Gene Therapy Science, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

2007-03-09

162

Transcriptional regulation of bone formation by the osteoblast-specific transcription factor Osx  

PubMed Central

Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells to osteoblasts. Osteoblast differentiation occurs through a multi-step molecular pathway regulated by different transcription factors and signaling proteins. Osx (also known as Sp7) is the only osteoblast-specific transcriptional factor identified so far which is required for osteoblast differentiation and bone formation. Osx knock-out mice lack bone completely and cartilage is normal. This opens a new window to the whole research field of bone formation. Osx inhibits Wnt pathway signaling, a possible mechanism for Osx to inhibit osteoblast proliferation. These reports demonstrate that Osx is the master gene that controls osteoblast lineage commitment and the subsequent osteoblast proliferation and differentiation. This review is to highlight recent progress in understanding the molecular mechanisms of transcriptional regulation of bone formation by Osx.

2010-01-01

163

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

Microsoft Academic Search

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

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

2011-01-01

164

Comparing histological, vascular and molecular responses associated with woven and lamellar bone formation induced by mechanical loading in the rat ulna  

PubMed Central

Osteogenesis occurs by formation of woven or lamellar bone. Little is known about the molecular regulation of these two distinct processes. We stimulated periosteal bone formation at the ulnar mid-diaphysis of adult rats using a single bout of forelimb compression. We hypothesized that loading that stimulates woven bone formation induces higher over-expression of genes associated with cell proliferation, angiogenesis and osteogenesis compared to loading that stimulates lamellar bone formation. We first confirmed that a single bout of 100 cycles of loading using either a rest-inserted (0.1 Hz) or haversine (2 Hz) waveform (15 N peak force) was non-damaging and increased lamellar bone formation (LBF loading). Woven bone formation (WBF loading) was stimulated using a previously described, damaging fatigue loading protocol (2 Hz, 1.3 mm disp., 18 N peak force). There were dramatic differences in gene expression levels (based on qRT-PCR) between loading protocols that produced woven and lamellar bone. In contrast, gene expression levels were not different between LBF loading protocols using a rest-inserted or haversine waveform. Cell proliferation markers Hist4 and Ccnd1 were strongly upregulated (5- to 17-fold) 1 and 3 days after WBF loading, prior to woven bone formation, but not after LBF loading. The angiogenic genes Vegf and Hif1a were upregulated within 1 hr after WBF loading and were strongly up on days 1-3 (3- to 15-fold). In sharp contrast, we observed only a modest increase (< 2-fold) in Vegfa and Hif1a expression on day 3 following LBF loading. Consistent with these relative differences in gene expression, vascular perfusion 3 days after loading revealed significant increases in vessel number and volume following WBF loading, but not after LBF loading. Lastly, bone formation markers (Runx2, Osx, Bsp) were more strongly upregulated for woven (4- to 89-fold) than for lamellar bone (2-fold), consistent with the differences in new bone volume observed 10 days after loading. In summary, robust early increases both molecularly and histologically for cell proliferation and angiogenesis precede woven bone formation, whereas lamellar bone formation is associated with only a modest upregulation of molecular signals at later timepoints.

McKenzie, Jennifer A.; Silva, Matthew J.

2010-01-01

165

Early Phases and Initial Conditions for Massive Star Formation  

Microsoft Academic Search

Our knowledge of the initial conditions and early stages of high mass star\\u000aformation is very limited. We will review recent surveys of regions in the\\u000aearly stages of massive star formation using molecular tracers of high density\\u000aand dust continuum emission and consider the status of evolutionary schemes.\\u000aComparison to the situation for low mass, relatively isolated star formation

Neal J. Evans II; Yancy L. Shirley; Kaisa E. Mueller; Claudia Knez

2001-01-01

166

VEGF and its role in the early development of the long bone epiphysis.  

PubMed

In long bones of murine species, undisturbed development of the epiphysis depends on the generation of vascularized cartilage canals shortly after birth. Despite its importance, it is still under discussion how this event is exactly regulated. It was suggested previously that, following increased hypoxia in the epiphyseal core, angiogenic factors are expressed and hence stimulate the ingrowth of the vascularized canals. In the present study, we tested this model and examined the spatio-temporal distribution of two angiogenic molecules during early development in mice. In addition, we investigated the onset of cartilage hypertrophy and mineralization. Our results provide evidence that the vascular endothelial growth factor is expressed in the epiphyseal resting cartilage prior to the moment of canal formation and is continuously expressed until the establishment of a large secondary ossification centre. Interestingly, we found no expression of secretoneurin before the establishment of the canals although this factor attracts blood vessels under hypoxic conditions. Epiphyseal development further involves maturation of the resting chondrocytes into hypertrophic ones, associated with the mineralization of the cartilage matrix and eventual death of the latter cells. Our results suggest that vascular endothelial growth factor is the critical molecule for the generation of the epiphyseal vascular network in mice long bones. Secretoneurin, however, does not appear to be a player in this event. Hypertrophic chondrocytes undergo cell death by a mechanism interpreted as chondroptosis. PMID:20525089

Allerstorfer, Doris; Longato, Stefano; Schwarzer, Christoph; Fischer-Colbrie, Reiner; Hayman, Alison R; Blumer, Michael J F

2010-05-01

167

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.

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

2008-01-01

168

Feeding blueberry diets during early development is sufficient to prevent senescence of osteoblasts and bone loss in adulthood  

Technology Transfer Automated Retrieval System (TEKTRAN)

Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented...

169

Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats  

Technology Transfer Automated Retrieval System (TEKTRAN)

Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we show that feeding a high quality diet supplemented...

170

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

NASA Astrophysics Data System (ADS)

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

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

171

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.

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

172

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

PubMed

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

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

2010-04-27

173

Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice  

PubMed Central

We describe the effects of the overexpression of noggin, a bone morphogenetic protein (BMP) inhibitor, on osteoblast differentiation and bone formation. Cells of the osteoblast and chondrocyte lineages, as well as bone marrow macrophages, showed intense ?-gal histo- or cytostaining in adult noggin+/– mice that had a LacZ transgene inserted at the site of noggin deletion. Despite identical BMP levels, however, osteoblasts of 20-month-old C57BL/6J and 4-month-old senescence-accelerated mice (SAM-P6 mice) had noggin expression levels that were approximately fourfold higher than those of 4-month-old C57BL/6J and SAM-R1 (control) mice, respectively. U-33 preosteoblastic cells overexpressing the noggin gene showed defective maturation and, in parallel, a decreased expression of Runx-2, bone sialoprotein, osteocalcin, and RANK-L. Noggin did not inhibit the ligandless signaling and pro-differentiation action of the constitutively activated BMP receptor type 1A, ca-ALK-3. Transgenic mice overexpressing noggin in mature osteocalcin-positive osteoblasts showed dramatic decreases in bone mineral density and bone formation rates with histological evidence of decreased trabecular bone and CFU-osteoblast colonies at 4 and 8 months. Together, the results provide compelling evidence that noggin, expressed in mature osteoblasts, inhibits osteoblast differentiation and bone formation. Thus, the overproduction of noggin during biological aging may result in impaired osteoblast formation and function and hence, net bone loss.

Wu, Xue-Bin; Li, Yanan; Schneider, Adina; Yu, Wanqin; Rajendren, Gopalan; Iqbal, Jameel; Yamamoto, Matsuo; Alam, Mohammad; Brunet, Lisa J.; Blair, Harry C.; Zaidi, Mone; Abe, Etsuko

2003-01-01

174

Accelerated and Enhanced Bone Formation on Novel Simvastatin-Loaded Porous Titanium Oxide Surfaces.  

PubMed

BACKGROUND: With increasing application of dental implants in poor-quality bones, the need for implant surfaces ensuring accelerated osseointegration and enhanced peri-implant bone regeneration is increased. PURPOSE: A study was performed to evaluate the osseointegration and bone formation on novel simvastatin-loaded porous titanium oxide surface. MATERIALS AND METHODS: Titanium screws were treated by micro-arc oxidation to form porous oxide surface and 25 or 50??g of simvastatin was loaded. The nontreated control, micro-arc oxidized, and simvastatin-loaded titanium screws were surgically implanted into the proximal tibia of 16-week-old male Wistar rats (n?=?36). Peri-implant bone volume, bone-implant contact, and mineral apposition rates were measured at 2 and 4 weeks. Data were analyzed by one-way analysis of variance followed by Tukey's post hoc test. RESULTS: New bone was formed directly on the implant surface in the bone marrow cavity in simvastatin-loaded groups since 2 weeks. Bone-implant contact values were significantly higher in simvastatin-loaded groups than control and micro-arc oxidized groups at both time points (p?bone volume and mineral apposition rate of simvastatin-loaded groups were significantly higher than control and micro-arc oxidized groups at 2 weeks (p?bone formation and it would be potentially applicable in poor-quality bones. PMID:23399109

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

2013-02-01

175

Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation  

PubMed Central

Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts and is key to the maintenance of bone integrity. While bone matrix–mobilized growth factors, such as TGF-?, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule serves as a coupling factor for bone resorption to formation. We found that CTHRC1, a protein secreted by mature bone-resorbing osteoclasts, targets stromal cells to stimulate osteogenesis. Cthrc1 expression was robustly induced when mature osteoclasts were placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increased in a high-turnover state (such as that induced by RANKL injections in vivo), but decreased in conditions associated with suppressed bone turnover (such as with aging and after alendronate treatment). Targeted deletion of Cthrc1 in mice eliminated Cthrc1 expression in bone, whereas its deficiency in osteoblasts did not exert any significant effect. Osteoclast-specific deletion of Cthrc1 resulted in osteopenia due to reduced bone formation and impaired the coupling process after resorption induced by RANKL injections, impairing bone mass recovery. These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling.

Takeshita, Sunao; Fumoto, Toshio; Matsuoka, Kazuhiko; Park, Kyoung-ae; Aburatani, Hiroyuki; Kato, Shigeaki; Ito, Masako; Ikeda, Kyoji

2013-01-01

176

Osteoclast-secreted CTHRC1 in the coupling of bone resorption to formation.  

PubMed

Bone remodeling is characterized by the sequential, local tethering of osteoclasts and osteoblasts and is key to the maintenance of bone integrity. While bone matrix-mobilized growth factors, such as TGF-?, are proposed to regulate remodeling, no in vivo evidence exists that an osteoclast-produced molecule serves as a coupling factor for bone resorption to formation. We found that CTHRC1, a protein secreted by mature bone-resorbing osteoclasts, targets stromal cells to stimulate osteogenesis. Cthrc1 expression was robustly induced when mature osteoclasts were placed on dentin or hydroxyapatite, and also by increasing extracellular calcium. Cthrc1 expression in bone increased in a high-turnover state (such as that induced by RANKL injections in vivo), but decreased in conditions associated with suppressed bone turnover (such as with aging and after alendronate treatment). Targeted deletion of Cthrc1 in mice eliminated Cthrc1 expression in bone, whereas its deficiency in osteoblasts did not exert any significant effect. Osteoclast-specific deletion of Cthrc1 resulted in osteopenia due to reduced bone formation and impaired the coupling process after resorption induced by RANKL injections, impairing bone mass recovery. These data demonstrate that CTHRC1 is an osteoclast-secreted coupling factor that regulates bone remodeling. PMID:23908115

Takeshita, Sunao; Fumoto, Toshio; Matsuoka, Kazuhiko; Park, Kyoung-ae; Aburatani, Hiroyuki; Kato, Shigeaki; Ito, Masako; Ikeda, Kyoji

2013-08-01

177

Alterations to bone mineral composition as an early indication of osteomyelitis in the diabetic foot.  

PubMed

OBJECTIVE Osteomyelitis in the diabetic foot is a major risk factor for amputation, but there is a limited understanding of early-stage infection, impeding limb-preserving diagnoses. We hypothesized that bone composition measurements provide insight into the early pathophysiology of diabetic osteomyelitis. RESEARCH DESIGN AND METHODS Compositional analysis by Raman spectroscopy was performed on bone specimens from patients with a clinical diagnosis of osteomyelitis in the foot requiring surgical intervention as either a biopsy (n = 6) or an amputation (n = 11). RESULTS An unexpected result was the discovery of pathological calcium phosphate minerals in addition to normal bone mineral. Dicalcium phosphate dihydrate, also called brushite, and uncarbonated apatite were found to be exclusively associated with infected bone. CONCLUSIONS Compositional measurements provided a unique insight into the pathophysiology of osteomyelitis in diabetic foot ulcers. At-patient identification of pathological minerals by Raman spectroscopy may serve as an early-stage diagnostic approach. PMID:23920085

Esmonde-White, Karen A; Esmonde-White, Francis W L; Holmes, Crystal M; Morris, Michael D; Roessler, Blake J

2013-08-06

178

Two models of early weaning decreases bone structure by different changes in hormonal regulation of bone metabolism in neonate rat.  

PubMed

During the last decade a great concern has developed for determining what factors influence bone mineral accretion in healthy children. Mother's milk represents the primary source of calcium and other nutrients in the neonate. The development of bone and adipose tissue has common origins. Since early weaning decreases adipogenesis in neonate, our aim was to evaluate bone metabolism in 2 models of early weaning (EW) in neonate rats. Lactating rats were separated into 3 groups: control: pups had free access to milk; MEW: dams were involved with a bandage mechanically (M) interrupting lactation in the last 3 days; and PEW: dams were pharmacologically (P) treated to block prolactin (0.5 mg bromocryptine/twice a day) 3 days before standard weaning. Significant difference had p<0.05. At weaning, MEW and PEW pups presented lower body weight (-18% and -15%), total body fat (-26% and -27%), total bone mineral density (-7% and -6%), total bone mineral content (-30% and -32%), bone area (-28% and -30%), serum osteocalcin (-20% and -55%), and higher C-terminal cross-linked telopeptide of type I collagen (CTX-I) (1.3 and 1.1-fold increase). However, serum ionized calcium was lower only in MEW pups (-34%), 25-hydroxyvitamin D was higher (1.4-fold increase), and PTH was lower (-26%) only in PEW group. The present study shows that both early weaning models leads to an impairment of osteogenesis associated with lower adipogenesis by different mechanisms, involving mainly changes in vitamin D and PTH. PMID:23264036

de Albuquerque Maia, L; Lisboa, P C; de Oliveira, E; da Silva Lima, N; da Costa, C A S; de Moura, E G

2012-12-21

179

Star Formation Signatures in Optically Quiescent Early-type Galaxies  

Microsoft Academic Search

In recent years, an argument has been made that a high fraction of early-type galaxies (ETGs) in the local universe experience low levels (lsim1 M sun yr-1) of star formation (SF) that causes strong excess in UV flux, yet leaves the optical colors red. Many of these studies were based on Galaxy Evolution Explorer imaging of Sloan Digital Sky Survey

Samir Salim; R. Michael Rich

2010-01-01

180

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

181

Bone formation by vascularized periosteal and osteoperiosteal grafts. An experimental study in rats.  

PubMed

The osteogenic capacity of vascularized periosteal and osteoperiosteal grafts was investigated in 82 Wistar rats about 8 weeks old. The periosteal flaps, pedicled on the descending genicular artery, were taken by stripping the lower third of the femur. In the right hindleg, the grafts were made with periosteum only, while in the left hindleg, the periosteal flaps were associated with cancellous bone. The animals were divided into two groups of 41. In group I, both the periosteal and osteoperiosteal grafts were placed in contact with cortical bone, and in group II, the grafts were buried in muscle. Subgroups of 8 animals were killed after 1, 2, 4, 8, and 16 weeks postoperatively. The grafted region was evaluated radiographically, macroscopically, and histologically. Membranous ossification was the main source of bone formation. Osteoperiosteal grafts produced a greater amount of new bone than periosteal ones. There was evidence that the contact of the graft with living cortical bone favored bone formation. PMID:7696043

Camilli, J A; Penteado, C V

1994-01-01

182

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.

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

183

Ultrasound Enhances Recombinant Human BMP2 Induced Ectopic Bone Formation in a Rat Model  

Microsoft Academic Search

Two methods to improve bone repair include the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-intensity pulsed ultrasound (LIPUS). The present study was designed to determine if LIPUS enhances the effect of rhBMP-2–induced bone formation in a well characterized ectopic implant model. Absorbable collagen sponges loaded with 0-, 1-, 2.5- or 5-?g doses of rhBMP-2 were implanted subcutaneously

Coen A. Wijdicks; Amarjit S. Virdi; Kotaro Sena; Dale R. Sumner; Robert M. Leven

2009-01-01

184

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.

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

2009-01-01

185

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

186

Early Stages of the HIV-1 Capsid Protein Lattice Formation  

PubMed Central

The early stages in the formation of the HIV-1 capsid (CA) protein lattice are investigated. The underlying coarse-grained (CG) model is parameterized directly from experimental data and examined under various native contact interaction strengths, CA dimer interfacial configurations, and local surface curvatures. The mechanism of early contiguous mature-style CA p6 lattice formation is explored, and a trimer-of-dimers structure is found to be crucial for CA lattice production. Quasi-equivalent generation of both the pentamer and hexamer components of the HIV-1 viral CA is also demonstrated, and the formation of pentamers is shown to be highly sensitive to local curvature, supporting the view that such inclusions in high-curvature regions allow closure of the viral CA surface. The complicated behavior of CA lattice self-assembly is shown to be reducible to a relatively simple function of the trimer-of-dimers behavior.

Grime, John M.A.; Voth, Gregory A.

2012-01-01

187

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

PubMed

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/?CT imaging. GSK-3 inhibitors caused ?-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28days exposure in rats. After 7days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH1-34 or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/?CT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. PMID:23872097

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

2013-07-18

188

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

189

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.

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

2012-01-01

190

Method for Fostering Bone Formation and Preservation (PAT-APPL-11-267 987).  

National Technical Information Service (NTIS)

A method of inducing bone formation in a subject in need of such inducement comprises the steps of mechanically inducing an increase in osteoblast activity in the subject and elevating blood concentration of at least one bone anabolic agent in the subject...

A. Vignery J. P. Gilligan N. M. Mehta

2005-01-01

191

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

192

Mineralization and bone formation on microcarrier beads with isolated rat calvaria cell population  

Microsoft Academic Search

Using enzymatically isolated rat bone cells in the presence of cytodex microcarrier beads, osteoblastic cell differentiation and bone nodule formation were studied at the optical and electron microscopic level. Cytochemical method showed an intense alkaline phosphatase activity mainly around the microcarriers where the cells have formed multilayers on day 4 of cultures. On day 7 of experiment cultures. Von Kossa

Jean-Michel Sautier; Jean-Raphaël Nefussi; Nadine Forest

1992-01-01

193

INHIBITION OF DIRECT BONE FORMATION ASSOCIATED WITH CHRONIC ETHANOL EXPOSURE IN A MOUSE MODEL OF DISTRACTIONOSTEOGENESIS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Excessive alcohol consumption has been reported to interfere with human bone homeostasis and repair in multiple ways. Previous studies have demonstrated that chronic ethanol (EtOH) exposure in the rat inhibits direct bone formation during distraction osteogenesis (DO, limb lengthening). The opportun...

194

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

Microsoft Academic Search

The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in Cbfa1-deficient

P. Ducy; M. Starbuck; M. Priemel; J. Shen; G. Pinero; V. Geoffroy; M. Amling; G. Karsenty

1999-01-01

195

An electronic device for accelerating bone formation in tissues surrounding a dental implant  

Microsoft Academic Search

A dental implant is a unique structure which can be used with a noninvasive method because it is inserted into the bone in part and extended extracorporally. This study presents an electronic device that is temporarily connected with the dental implant, and reports its effect on accelerating bone formation in the surrounding tissues in a canine mandibular model. A small

Jong K. Song; Tae H. Cho; Hui Pan; Yoon M. Song; In S. Kim; Tae H. Lee; Soon J. Hwang; Sung J. Kim

2009-01-01

196

Pharmacokinetics and bone formation by BMP2 entrapped in polyethylenimine-coated albumin nanoparticles  

Microsoft Academic Search

The osteoinductive growth factor, bone morphogenetic protein-2 (BMP-2), is capable of inducing de novo bone formation after implantation. A nanoparticulate (NP) system was developed for BMP-2 delivery based on NPs fabricated from bovine serum albumin (BSA) and stabilized by polyethylenimine (PEI) coating. In this study, the pharmacokinetics and osteoinductivity of BMP-2 delivered with different BSA NP formulations were determined by

Sufeng Zhang; Michael R. Doschak; Hasan Uluda?

2009-01-01

197

(18)F-fluoride Positron Emission Tomography Measurements of Regional Bone Formation in Hemodialysis Patients with Suspected Adynamic Bone Disease.  

PubMed

(18)F-fluoride positron emission tomography ((18)F-PET) allows the assessment of regional bone formation and could have a role in the diagnosis of adynamic bone disease (ABD) in patients with chronic kidney disease (CKD). The purpose of this study was to examine bone formation at multiple sites of the skeleton in hemodialysis patients (CKD5D) and assess the correlation with bone biopsy. Seven CKD5D patients with suspected ABD and 12 osteoporotic postmenopausal women underwent an (18)F-PET scan, and bone plasma clearance, K i, was measured at ten skeletal regions of interest (ROI). Fifteen subjects had a transiliac bone biopsy following double tetracycline labeling. Two CKD5D patients had ABD confirmed by biopsy. There was significant heterogeneity in K i between skeletal sites, ranging from 0.008 at the forearm to 0.028 mL/min/mL at the spine in the CKD5D group. There were no significant differences in K i between the two study groups or between the two subjects with ABD and the other CKD5D subjects at any skeletal ROI. Five biopsies from the CKD5D patients had single tetracycline labels only, including the two with ABD. Using an imputed value of 0.3 ?m/day for mineral apposition rate (MAR) for biopsies with single labels, no significant correlations were observed between lumbar spine K i corrected for BMAD (K i/BMAD) and bone formation rate (BFR/BS), or MAR. When biopsies with single labels were excluded, a significant correlation was observed between K i/BMAD and MAR (r = 0.81, p = 0.008) but not BFR/BS. Further studies are required to establish the sensitivity of (18)F-PET as a diagnostic tool for identifying CKD patients with ABD. PMID:23995764

Frost, Michelle L; Compston, Juliet E; Goldsmith, David; Moore, Amelia E; Blake, Glen M; Siddique, Musib; Skingle, Linda; Fogelman, Ignac

2013-08-31

198

[Bone architecture and strength on unloading].  

PubMed

The bone loss due to space flight or prolonged bed rest observes early stage of unloading and causes both decreased bone formation and increased bone resorption. Mechanical unloading induced not only both tarbecular and cortical bone loss but also greater decline bone structure in weight-bearing bone. These findings and further examination concern about pathophysiolosy will allow for better understanding of unloading-associated bone loss and for development of effective countermeasures. PMID:23811590

Endo, Itsuro; Matsumoto, Toshio

2013-07-01

199

Effect of fluoride-substituted apatite on in vivo bone formation.  

PubMed

Biological apatites are characterized by the presence of minor constituents such as magnesium (Mg), chloride (Cl), or fluoride (F) ions. These ions affect cell proliferation and osteoblastic differentiation during bone tissue formation. F-substituted apatites are being explored as potential bonegraft materials. The aim of the present study is to investigate the mechanism of bone formation induced by fluoride-substituted apatite (FAp) by analyzing the effect of FAp on the process of in vivo bone formation. FAps containing different F concentrations (l-FAp: 0.48 wt%, m-FAp: 0.91 wt%, h-FAp: 2.23 wt%) and calcium-deficient apatite (CDA), as positive control, were implanted in rat tibia and bone formation was evaluated by histological examination, immuhistochemistry, in situ hybridization and tartrate-resistant acid phosphatase examinations. The results showed that l-FAp, m-FAp, h-FAp, and CDA biomaterials allowed migration of macrophages, attachment, proliferation, and phenotypic expression of bone cells leading to new bone formation in direct apposition to the particles. However, the l-FAp preparation allowed faster bone conduction compared to the other experimental materials. These results suggest that FAp with low F concentration may be an efficient bonegraft material for dental and medical application. PMID:20219846

Inoue, Miho; Rodriguez, Andrea P; Nagai, Noriyuki; Nagatsuka, Hitoshi; LeGeros, Racquel Z; Tsujigiwa, Hidetsugu; Inoue, Masahisa; Kishimoto, Etsuo; Takagi, Shin

2010-03-10

200

DETERMINANTS OF BONE CALCIUM ACCRETION DURING EARLY ADOLESCENCE  

Technology Transfer Automated Retrieval System (TEKTRAN)

Bone mineral status during adolescence may be related to genetic and dietary factors. We evaluated 49 female and 49 male adolescents (Tanner 2/3) randomized to receive 8g of Synergl (Orafti Inc., Belgium), a non-digestible inulin-type fructan daily for a year or placebo. Fractional calcium (Ca) abso...

201

Rat bone marrow stem cells isolation and culture as a bone formative experimental system.  

PubMed

Bone marrow mesenchymal cells have been identified as a source of pluripotent stem cells with multipotential potential and differentiation in to the different cells types such as are osteoblast, chondroblast, adipoblast. In this research we describe pioneering experiment of tissue engineering in Bosnia and Herzegovina, of the isolation and differentiation rat bone marrow stromal cells in to the osteoblast cells lineages. Rat bone marrow stromal cells were isolated by method described by Maniatopulos using their plastic adherence capatibility. The cells obtained by plastic adherence were cultured and serially passaged in the osteoinductive medium to differentiate into the osteocytes. Bone marrow samples from rats long bones used for isolation of stromal cells (BMSCs). Under determinate culture conditions BMSCs were differentiated in osteogenic cell lines detected by Alizarin red staining three weeks after isolation. BMSCs as autologue cells model showed high osteogenetic potential and calcification capatibility in vitro. In future should be used as alternative method for bone transplantation in Regenerative Medicine. PMID:23448607

Smajilagi?, Amer; Alji?evi?, Mufida; Redži?, Amira; Filipovi?, Selma; Lagumdžija, Alena

2013-02-01

202

Local effects of impaired mechanical properties of collagen on bone formation and resorption  

Microsoft Academic Search

Summary To study the relationship between the mechanical properties of collagen and the bone turnover, 2-week-old Balb\\/C mice were fed on a diet containing 0.25% Beta aminopropionitrile (B-APN), a potent inhibitor of collagen crosslink formation, for 3 weeks. Mandibular incisor socket was selected for the analysis of bone formation and resorption parameters. Plastic embedded sections stained with toludine blue and

A. Kwong-Hing; R. Teasdale; H. S. Sandhu

1991-01-01

203

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

PubMed Central

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

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

2008-01-01

204

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

2007-10-25

205

Effect of Autologous Bone Marrow Stromal Cell Seeding and Bone Morphogenetic Protein-2 Delivery on Ectopic Bone Formation in a Microsphere/Poly(Propylene Fumarate) Composite  

PubMed Central

A biodegradable microsphere/scaffold composite based on the synthetic polymer poly(propylene fumarate) (PPF) holds promise as a scaffold for cell growth and sustained delivery vehicle for growth factors for bone regeneration. The objective of the current work was to investigate the in vitro release and in vivo bone forming capacity of this microsphere/scaffold composite containing bone morphogenetic protein-2 (BMP-2) in combination with autologous bone marrow stromal cells (BMSCs) in a goat ectopic implantation model. Three composites consisting of 0, 0.08, or 8??g BMP-2?per mg of poly(lactic-co-glycolic acid) microspheres, embedded in a porous PPF scaffold, were combined with either plasma (no cells) or culture-expanded BMSCs. PPF scaffolds impregnated with a BMP-2 solution and combined with BMSCs as well as empty PPF scaffolds were also tested. The eight different composites were implanted subcutaneously in the dorsal thoracolumbar area of goats. Incorporation of BMP-2–loaded microspheres in the PPF scaffold resulted in a more sustained in vitro release with a lower burst phase, as compared to BMP-2–impregnated scaffolds. Histological analysis after 9 weeks of implantation showed bone formation in the pores of 11/16 composites containing 8??g/mg BMP-2–loaded microspheres with no significant difference between composites with or without BMSCs (6/8 and 5/8, respectively). Bone formation was also observed in 1/8 of the BMP-2–impregnated scaffolds. No bone formation was observed in the other conditions. Overall, this study shows the feasibility of bone induction by BMP-2 release from microspheres/scaffold composites.

Kempen, Diederik H.R.; Kruyt, Moyo C.; Lu, Lichun; Wilson, Clayton E.; Florschutz, Anthony V.; Yaszemski, Michael J.; Dhert, Wouter J.A.

2009-01-01

206

Porous ceramic titanium dioxide scaffolds promote bone formation in rabbit peri-implant cortical defect model.  

PubMed

Titanium oxide (TiO?) scaffolds have previously been reported to exhibit very low mechanical strength. However, we have been able to produce a scaffold that features a high interconnectivity, a porosity of 91% and a compressive strength above 1.2 MPa. This study analyzed the in vivo performance of the porous TiO? scaffolds in a peri-implant cortical defect model in the rabbit. After 8 weeks of healing, morphological microcomputed tomography analyses of the defects treated with the TiO? scaffolds had significantly higher bone volume, bone surface and bone surface-to-volume ratio when compared to sham, both in the cortical and bone marrow compartment. No adverse effects, i.e. tissue necrosis or inflammation as measured by lactate dehydrogenase activity and real-time reverse transcription polymerase chain reaction analysis, were observed. Moreover, the scaffold did not hinder bone growth onto the adjacent cortical titanium implant. Histology clearly demonstrated new bone formation in the cortical sections of the defects and the presence of newly formed bone in close proximity to the scaffold surface and the surface of the adjacent Ti implant. Bone-to-material contact between the newly formed bone and the scaffold was observed in the histological sections. Islets of new bone were also present in the marrow compartment albeit in small amounts. In conclusion, the present investigation demonstrates that TiO? scaffolds osseointegrate well and are a suitable scaffold for peri-implant bone healing and growth. PMID:22985740

Haugen, Håvard Jostein; Monjo, Marta; Rubert, Marina; Verket, Anders; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Rønold, Hans Jacob; Wohlfahrt, Johan Caspar

2012-09-14

207

Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients.  

PubMed

Fragility fractures, including neck of femur fractures, result from reductions in the amount, quality and architecture of bone. The aim of this study was to compare the cancellous bone structure, and static indices of bone turnover, in female patients, who had sustained fragility fracture at the femoral neck, with age-matched females without fragility fracture. Bone samples were taken from the intertrochanteric region of the proximal femur of female patients undergoing hip arthroplasty surgery for a subcapital fragility fracture of the femoral neck (#NOF) or from age-matched female control individuals at routine autopsy. Contiguous bone samples were analyzed for undecalcified histomorphometry and for mRNA expression. The histomorphometric data, which were normally distributed, indicated no difference between the mean values for any of the structural parameters in control and fracture samples. In particular, the bone volume (BV/TV) values were not different and did not change significantly with age in these cohorts of individuals aged >65 years. The static indices of bone turnover, eroded surface (ES/BS) and osteoid surface (OS/BS), were positively correlated with age in the >65-year-old control group (p < 0.055 and p < 0.03, respectively). The median values for these indices were not different between the fracture and control groups. However, both the median and the range of OS/BS values were increased for >65-year-old controls compared with a group of younger females aged <65 years, suggesting an increase in bone formation surface in older females in the proximal femur after 65 years of age. When the data were further interrogated, a reduction in the percentage osteoid surface to eroded surface quotient (OS/ES) was found for the fracture group compared with the age-matched control group suggesting a reduced adaptive modeling drift capability in the fracture group. In contiguous bone samples, increased median values for receptor activator of nuclear factor kappa beta (RANK) and interleukin-6 (IL-6) mRNA expression were observed in the fracture group. Study of cultured human osteoblasts showed that recombinant human IL-6 (rhIL-6) inhibited osteoblast differentiation, as measured by an increase in the immature osteoblast marker, STRO-1 and concomitantly decreased expression of the osteoblast maturation marker, alkaline phosphatase. Importantly, cells cultured in the presence of IL-6 showed significantly less mineral deposition in vitro compared with control cultures. These data suggest that perturbations in bone formation surface, relative to resorption surface, are potentially important in producing bone in the proximal femur with increased propensity to fracture. PMID:16926124

Tsangari, Helen; Findlay, David M; Zannettino, Andrew C W; Pan, Beiqing; Kuliwaba, Julia S; Fazzalari, Nicola L

2006-08-22

208

Targeting the Wnt signaling pathway to augment bone formation  

Microsoft Academic Search

Recent discoveries in humans and mice have revealed that the Wnt (Wingless and Int-1) signaling pathway is responsible for\\u000a a complex array of functions in maintaining bone homeostasis. The Wnt proteins are key modulators of mesenchymal lineage specification\\u000a and regulate most aspects of osteoblast physiology and postnatal bone acquisition by controlling the differentiation and activity\\u000a of osteoblasts and osteoclasts. Initial

Mohammad Shahnazari; Wei Yao; Maripat Corr

2008-01-01

209

Bone density, strength, and formation in adult cathepsin K (?\\/?) mice  

Microsoft Academic Search

Cathepsin K (CatK) is a cysteine protease expressed predominantly in osteoclasts, that plays a prominent role in degrading Type I collagen. Growing CatK null mice have osteopetrosis associated with a reduced ability to degrade bone matrix. Bone strength and histomorphometric endpoints in young adult CatK null mice aged more than 10 weeks have not been studied. The purpose of this paper

B. Pennypacker; M. Shea; Q. Liu; P. Masarachia; P. Saftig; S. Rodan; G. Rodan; D. Kimmel

2009-01-01

210

Brucella abortus Invasion of Osteoblasts Inhibits Bone Formation  

PubMed Central

Osteoarticular brucellosis is the most common presentation of the active disease in humans. Loss of bone is a serious complication of localized bacterial infection of bones or the adjacent tissue, and brucellosis proved not to be the exception. The skeleton is a dynamic organ system which is constantly remodeled. Osteoblasts are responsible for the deposition of bone matrix and are thought to facilitate the calcification and mineralization of the bone matrix, and their function could be altered under infectious conditions. In this article, we describe immune mechanisms whereby Brucella abortus may invade and replicate within osteoblasts, inducing apoptosis, inhibiting mineral and organic matrix deposition, and inducing upregulation of RANKL expression. Additionally, all of these mechanisms contributed in different ways to bone loss. These processes implicate the activation of signaling pathways (mitogen-activated protein kinases [MAPK] and caspases) involved in cytokine secretion, expression of activating molecules, and cell death of osteoblasts. In addition, considering the relevance of macrophages in intracellular Brucella survival and proinflammatory cytokine secretion in response to infection, we also investigated the role of these cells as modulators of osteoblast survival, differentiation, and function. We demonstrated that supernatants from B. abortus-infected macrophages may also mediate osteoblast apoptosis and inhibit osteoblast function in a process that is dependent on the presence of tumor necrosis factor alpha (TNF-?). These results indicate that B. abortus may directly and indirectly harm osteoblast function, contributing to the bone and joint destruction observed in patients with osteoarticular complications of brucellosis.

Scian, Romina; Barrionuevo, Paula; Fossati, Carlos A.; Giambartolomei, Guillermo H.

2012-01-01

211

Requirement of alveolar bone formation for eruption of rat molars  

PubMed Central

Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (BMP6), was inhibited by injection of the 1st mandibular molar of the rat with an siRNA targeted against BMP6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption either was delayed or completely inhibited (7 molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced as compared to the erupted first molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that BMP6 may be an essential gene for promoting this growth.

Wise, Gary E.; He, Hongzhi; Gutierrez, Dina L.; Ring, Sherry; Yao, Shaomian

2011-01-01

212

Could some biomechanical effects of growth hormone help to explain its effects on bone formation and resorption?  

Microsoft Academic Search

This article suggests that growth hormone effects on bone biomechanical factors help to cause changes in osteoblastic and osteoclastic activities in gigantism and growth-hormone-deficiency states. The suggestion stands partly on the following evidence. (1) In growing mammals, acute partial disuse decreases or stops longitudinal bone growth and periosteal bone formation and increases in outside bone diameter. Yet, in metaphyseal spongiosa,

H. M. Frost

1998-01-01

213

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

PubMed

We generated a new Bmp2 conditional-knockout allele without a neo cassette that removes the Bmp2 gene from osteoblasts (Bmp2-cKO(ob)) using the 3.6Col1a1-Cre transgenic model. Bones of Bmp2-cKO(ob) 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-cKO(ob) 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

2013-07-10

214

Analysis of bone formation after cranial osteotomies with a high-speed drill.  

PubMed

Ten New Zealand white 22-week-old rabbits were divided into two groups of five each. The Midas Rex drill with a C-1 drill bit was used to make a full-thickness sagittal osteotomy 2 cm in length. A B-5 bit and footplate attachment were used to make a 2-cm linear osteotomy parallel to the first. Four drill holes 1 mm in diameter were made over the nasal bones on the ipsilateral side. In Group A animals, half of the skull had no irrigation; the other half of the skull was irrigated with room temperature saline. In Group B animals half of the skull was irrigated with iced saline irrigation; the other half of the skull was irrigated with room temperature irrigation fluid, and the osteotomy sites were filled with bone wax. Specimens were harvested at 8 weeks and evaluated grossly and histologically. The results showed that all the drill holes closed in the nasal bones regardless of the type of irrigation used or whether bone wax was used. Iced saline irrigation and room temperature irrigation had similar positive effects on bone formation in contrast to the no-irrigation group, which had inferior bone formation. Bone wax appeared also to have a detrimental effect on bone formation. PMID:9477832

Barone, C M; Jimenez, D F; Yule, G J; Strauch, B

1997-11-01

215

Bone scanning in patients with early breast carcinoma: should it be a routine staging procedure  

SciTech Connect

Bone scanning is a sensitive test for the detection of metastatic breast cancer, but not all abnormal findings on bone scan are diagnostic of skeletal metastasis. Recent studies have found a relatively low rate (less than or equal to 5%) of abnormal scans in patients with Stage I and II breast cancers, and only half of those with positive scans subsequently had documented bony metastasis. The overwhelming clinical experiences summarized here question the value of including bone scanning as part of the routine work-up of patients with early breast cancers.

Lee, Y.T.

1981-02-01

216

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

217

Fibrodysplasia ossificans progressiva (FOP): A human genetic disorder of extra-skeletal bone formation, or - How does one tissue become another?  

PubMed Central

Fibrodysplasia ossificans progressiva (FOP) is a rare human genetic disease in which de novo osteogenesis – a developmental process occurring during embryonic skeletal formation – is induced aberrantly and progressively beginning during early childhood in soft connective tissues. Episodic initiation of spontaneous bone forming lesions occurs over time, affecting a generally predictable sequence of body locations following a pattern similar to that of the developing embryonic skeleton. The heterotopic (extra-skeletal) bone formation in FOP can also be induced by connective tissue injury. At the tissue level, an initial tissue degradation phase is followed by a tissue formation phase during which soft connective tissues are replaced by bone tissue through endochondral osteogenesis. This extra-skeletal bone is physiologically normal and develops through the same series of tissue differentiation events that occurs during normal embryonic skeletal development. The underlying genetic mutation in FOP alters the signals that regulate induction of cell differentiation leading to bone formation. In addition to post-natal heterotopic ossification, FOP patients show specific malformations of skeletal elements indicating effects on bone formation during embryonic development as well. Nearly all cases of FOP are caused by the identical mutation in the ACVR1 gene that causes a single amino acid substitution, R206H, in the bone morphogenetic protein (BMP) type I receptor ACVR1 (formerly known as ALK2). This mutation causes mild constitutive activation of the BMP signaling pathway and identifies ACVR1 as a key regulator of cell fate decisions and bone formation, providing opportunities to investigate previously unrecognized functions for this receptor during tissue development and homeostasis.

Shore, Eileen M.

2011-01-01

218

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.

2011-01-01

219

Increased bone formation and osteosclerosis in mice overexpressing the transcription factor Fra-1.  

PubMed

Bone formation by osteoblasts is essential for skeletal growth and remodeling. Fra-1 is a c-Fos-related protein belonging to the AP-1 family of transcription factors. Here we show that transgenic mice overexpressing Fra-1 in various organs develop a progressive increase in bone mass leading to osteosclerosis of the entire skeleton, which is due to a cell-autonomous increase in the number of mature osteoblasts. Moreover, osteoblast differentiation, but not proliferation, was enhanced and osteoclastogenesis was also elevated in vitro. These data indicate that, unlike c-Fos, which causes osteosarcomas, Fra-1 specifically enhances bone formation, which may be exploited to stimulate bone formation in pathological conditions. PMID:10973316

Jochum, W; David, J P; Elliott, C; Wutz, A; Plenk, H; Matsuo, K; Wagner, E F

2000-09-01

220

Competitive physical activity early in life is associated with bone mineral density in elderly Swedish men  

Microsoft Academic Search

Summary  In this population-based study of 75-year-old men (n?=?498), we investigated the association between physical activity (PA) early in life and present bone mineral density (BMD).\\u000a We demonstrate that a high frequency of competitive sports early in life is associated with BMD at several bone sites, indicating\\u000a that increases in BMD following PA are preserved longer than previously believed.\\u000a \\u000a \\u000a \\u000a Introduction  Physical activity

M. Nilsson; C. Ohlsson; A. L. Eriksson; K. Frändin; M. Karlsson; Ö. Ljunggren; D. Mellström; M. Lorentzon

2008-01-01

221

Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients  

PubMed Central

Background Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy. Methods DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined. Results Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ? = 0.55 to ? = 0.80. Conclusions The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements.

2010-01-01

222

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

223

Expression of bone matrix proteins during de novo bone formation using a bovine collagen and platelet-rich plasma (prp)—an immunohistochemical analysis  

Microsoft Academic Search

This animal study (domestic pig) examined the bone formation after filling defined defects with autogenous bone or a collagen lyophilisat in combination with Platelet-rich-plasma (PRP) by evaluating bone matrix proteins. Six groups, both materials with and without PRP in two concentrations (+1, +2) were compared to untreated bone by means of immunohistochemistry at 2, 4, 12 and 26 weeks.BMP-2 expression

M. Thorwarth; S. Rupprecht; S. Falk; E. Felszeghy; J. Wiltfang; K. A. Schlegel

2005-01-01

224

Could nonunion tissue be transformed capable of bone formation by negative pressure: a new alternative to treat bone nonunion?  

PubMed

Despite substantial advances in orthopaedic surgery, bone nonunion is still a matter of debate for orthopaedic surgeon to provide optimal options on treatment of nonunion. Negative pressure therapy has already been successfully used in dealing with complex kinds of soft tissue healing. Some studies show that negative pressure can induce mesenchymal stem cells to differentiate into osteoblasts and others suggest that there are some mesenchymal-like cells existing in the nonunion tissue which can be re-activated and transformed into osteoblasts under some circumstance. We hypothesized that under negative pressure the mesenchymal-like cells can be transformed into osteoblasts in nonunion site. Under negative pressure, both "seeds" and "soils" can be made for new bone formation. If our hypothesis is proved to be corrected, it could be an innovative method to treat the bone nonunion. PMID:22285624

Wan, Jun; Wan, Jing; Li, Kang-hua; Lei, Guang-hua; Liao, Qian-de; Zhu, Yong; Hu, Yi-he; Zhang, Xiang-sheng

2012-01-27

225

Sustained BMP signaling in osteoblasts stimulates bone formation by promoting angiogenesis and osteoblast differentiation.  

PubMed

Angiogenesis and bone formation are tightly coupled during the formation of the skeleton. Bone morphogenetic protein (BMP) signaling is required for both bone development and angiogenesis. We recently identified endosome-associated FYVE-domain protein (endofin) as a Smad anchor for BMP receptor activation. Endofin contains a protein-phosphatase pp1c binding domain, which negatively modulates BMP signals through dephosphorylation of the BMP type I receptor. A single point mutation of endofin (F872A) disrupts interaction between the catalytic subunit pp1c and sensitizes BMP signaling in vitro. To study the functional impact of this mutation in vivo, we targeted expression of an endofin (F872A) transgene to osteoblasts. Mice expressing this mutant transgene had increased levels of phosphorylated Smad1 in osteoblasts and showed increased bone formation. Trabecular bone volume was significantly increased in the transgenic mice compared with the wildtype littermates with corresponding increases in trabecular bone thickness and number. Interestingly, the transgenic mice also had a pronounced increase in the density of the bone vasculature measured using contrast-enhanced microCT imaging of Microfil-perfused bones. The vessel surface and volume were both increased in association with elevated levels of vascular endothelial growth factor (VEGF) in osteoblasts. Endothelial sprouting from the endofin (F872A) mutant embryonic metatarsals cultured ex vivo was increased compared with controls and was abolished by an addition of a VEGF neutralizing antibody. In conclusion, osteoblast targeted expression of a mutant endofin protein lacking the pp1c binding activity results in sustained signaling of the BMP type I receptor, which increases bone formation and skeletal angiogenesis. PMID:19257813

Zhang, Fengjie; Qiu, Tao; Wu, Xiangwei; Wan, Chao; Shi, Weibin; Wang, Ying; Chen, Jian-guo; Wan, Mei; Clemens, Thomas L; Cao, Xu

2009-07-01

226

Exposure to Subcutaneously Implanted Uranium Dioxide Impairs Bone Formation  

Microsoft Academic Search

The introduction of uranium particles into subcutaneous tissue is a risk that affects workers engaged in the extraction, purification, and manufacture of uranium, as well as soldiers who are wounded with uranium shrapnel. The authors evaluated the effect of an internal source of an insoluble form of uranium on bone. Uranium dioxide powder (0.125 gm\\/kg body weight) was implanted subcutaneously

Paula L. Díaz Sylvester; Ricardo Lopez; Angela M. Ubios; Rómulo L. Cabrini

2002-01-01

227

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

228

A composite material model for improved bone formation.  

PubMed

The combination of synthetic polymers and calcium phosphates represent an improvement in the development of scaffolds for bone-tissue regeneration. Ideally, these composites provide both mechanically and architecturally enhanced performances; however, they often lack properties such as osteoconductivity and cell bioactivation. In this study we attempted to generate a composite bone substitute maximizing the available osteoconductive surface for cell adhesion and activity. Highly porous scaffolds were prepared through a particulate leaching method, combining poly-?-caprolactone (PCL) and hydroxyapatite (HA) particles, previously coated with a sucrose layer, to minimize their embedding by the polymer solution. Composite performances were evaluated both in vitro and in vivo. In PCL-sucrose-coated HA samples, the HA particles were almost completely exposed and physically distinct from the polymer mesh, while uncoated control samples showed ceramic granules massively covered by the polymer. In vivo results revealed a significant extent of bone deposition around all sucrose-coated HA granules, while only parts of the control uncoated HA granules were surrounded by bone matrix. These findings highlight the possibility of generating enhanced osteoconductive materials, basing the scaffold design on physiological and cellular concepts. PMID:20213628

Scaglione, Silvia; Lazzarini, Erica; Ilengo, Cristina; Quarto, Rodolfo

2010-10-01

229

Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis  

Microsoft Academic Search

Targeted therapies that neutralize tumour necrosis factor are often able to control the signs and symptoms of spondyloarthritis. However, recent animal model data and clinical observations indicate that control of inflammation may not be sufficient to impede disease progression toward ankylosis in these patients. Bone morphogenetic proteins and WNTs (wingless-type like) are likely to play an important role in ankylosis

Rik JU Lories; Frank P Luyten; Kurt de Vlam

2009-01-01

230

Elevated soft tissue activity in early but not delayed phase of bone scan in Klippel-Trenaunay syndrome.  

PubMed

Triple-phase bone scan is commonly used in the diagnosis of osteomyelitis. Elevated bone tracer activity in early but not delayed phase of the study favors cellulitis over osteomyelitis. We reported that Klippel-Trenaunay syndrome, a congenital disorder characterized by malformations of the capillary, venous, and lymphatic systems, can have images similar to cellulitis on triple-phase bone scan. PMID:23354038

Liu, Bin; Servaes, Sabah; Zhuang, Hongming

2013-03-01

231

Bone marrow transplantation for acute myelogenous leukemia: factors associated with early mortality  

SciTech Connect

Comprehensive data were reported to the International Bone Marrow Transplant Registry, Milwaukee, regarding 156 patients with acute myelogenous leukemia who were treated with allogeneic bone marrow transplantation between 1978 and 1980. The minimum observation period was 15 months after transplant and most deaths occurred within the first six months. Prognostic factors were evaluated for associations with early mortality or life-threatening complications. Most early deaths were due to infections, interstitial pneumonitis, and graft-v-host disease (GVHD). Multivariate analyses disclosed five factors with significant associations with early death or a major cause of early death: (1) disease status; (2) dose-rate of irradiation; (3) drug used to prevent GVHD; (4) severity of GVHD; and (5) dose of marrow cells.It is emphasized that several of the important prognostic factors are within the control of the referring physician or the transplant team.

Bortin, M.M.; Gale, R.P.; Kay, H.E.; Rimm, A.A.

1983-03-04

232

Influence of interfacial properties and inhomogeneity on formation of microdamage in bone  

NASA Astrophysics Data System (ADS)

Microdamage accumulation at the nanoscopic level of bone affects the overall mechanical behavior of the bone. This makes it necessary to study the mechanisms through which microdamage accumulation can take place at the nanoscopic level. Experiments on bone's different hierarchy are difficult because of the small sizes of these hierarchical structures. Prevention of bone fractures is greatly enhanced with the help of predictive computational tools and hence used to evaluate the effects of microdamage in bone. There are two main types of microdamage that can form in the bone; linear cracks and diffuse damage. The bone nanostructure consists of mineral platelets embedded in soft protein called collagen and can be treated as a composite material. In this study, a two-dimensional probabilistic finite element model of the bone nanostructure was developed to evaluate the likely formation of the microdamage in the nanostructure due to changes in material properties of the nanostructure. The influence of the microdamage formation due to the collagen-mineral interface strength and also the effects of inhomogeneity were studied. To study interfacial strength effects, cohesive elements using bilinear traction separation laws were used to simulate the behavior of the interface (by way of interfacial debonding) between the collegen-mineral layers. Random field theory was used to assign spatially correlated random variables in order to assign inhomogeneous material properties to the bone. Correlation lengths were used to control the level of inhomogeneity in the model. The analysis showed that the type of microdamage was significantly influenced by the strength of the mineral-collagen interface. Probabilistic failure analyses indicated that strong interfaces resulted in limited interfacial debonding and narrow stress concentrations around an initial defect in the mineral-collagen composite, thereby suggesting that the likely location of failure was in same plane of the initial defect. This led to the conclusion that the likely type of microdamage formation was linear cracks. With weaker interfaces, interfacial debonding was significant and wider stress concentrations were formed around the initial defect. The probabilistic analysis determined that with weaker strengths and significant interfacial debonding, the next likely location of failure was scattered away from the initial defect. This led to the conclusion that the likely type of microdamage formation would be diffuse damage. The influence on microdamage formation due to the inhomogeneity of the bone material was also evaluated and it was determined that the type of microdamage formation was not influenced by the inhomogeneity. Differences in correlation lengths did not influence the type of microdamage formation. It was determined that the interfacial strength was a greater influence on the microdamage formation than the material inhomogeneity.

Nakade, Rugved

233

Fibrous dysplasia of bone in the McCune-Albright syndrome: abnormalities in bone formation.  

PubMed Central

In addition to café-au-lait pigmentation patterns and hyperendocrinopathies, fibrous dysplasia of bone is a major finding in the McCune-Albright syndrome. Activating missense mutations of the Gs alpha gene leading to overactivity of adenylyl cyclase have been identified in patients with McCune-Albright syndrome, but the mechanism leading to the specific development of fibrous dysplasia in bone has not been elucidated. By means of specific peptide antisera and reverse transcriptase polymerase chain reaction in situ hybridization, we show that expression of Gs alpha and its mRNA is critically up-regulated during maturation of precursor osteogenic cells to normal osteoblast cells and that this pattern of expression is retained in fibrous dysplasia. A functional characterization of fibrous dysplastic tissues revealed that the fibrotic areas consist, in fact, of an excess of cells with phenotypic features of pre-osteogenic cells, whereas the lesional bone formed de novo within fibrotic areas represents the biosynthetic output of mature but abnormal osteoblasts. These cells are noted for peculiar changes in cell shape and interaction with matrix, which were mimicked in vitro by the effects of excess exogenous cAMP on human osteogenic cells. Osteoblasts involved with the de novo deposition of lesional bone in fibrous dysplasia produce a bone matrix enriched in certain anti-adhesion molecules (versican and osteonectin), and poor in the pro-adhesive molecules osteopontin and bone sialoprotein, which is in contrast to the high levels of these two proteins found in normal de novo bone. Our data indicate the need to reinterpret fibrous dysplasia of bone as a disease of cells in the osteogenic lineage, related to the effects of excess cAMP on bone cell function. They further suggest that a critical, physiological, maturation-related regulation of Gs alpha levels makes cells in the osteogenic lineage a natural target for the effects of mutations in the Gs alpha gene and may provide a clue as to why bone itself is affected in this somatic, mutation-dependent disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8

Riminucci, M.; Fisher, L. W.; Shenker, A.; Spiegel, A. M.; Bianco, P.; Gehron Robey, P.

1997-01-01

234

Heterochronically early decline of Hox expression prior to cartilage formation in the avian hindlimb zeugopod.  

PubMed

The fibula, a zeugopod bone in the hindlimb, exhibits various morphologies in tetrapod species. The fibula in some species has a similar length with the other zeugopod element, the tibia, while other species have obvious differences in the sizes of the two elements. In the avian hindlimb, for example, the fibula is extremely short, thin, and truncated. Basic morphology of the fibula is established during development, and cartilage primordium of the bone emerges in a certain region defined by a distinct combination of expression of Hox genes (Hox code). In order to elucidate how the different morphologies are produced from a region that is defined as the fixed Hox code, we examined spatial and temporal patterns of Hoxd11/Hoxd12 expression in the developing limb bud, which defines the region from which the fibula emerges, in comparison with the sites of precartilaginous mesenchymal condensations representing regions for cartilage formation among chick, mouse, and gecko embryos. We found that in the chick hindlimb, expression of Hoxd11/Hoxd12 decreased and disappeared from the presumptive zeugopod region before cartilage formation. This heterochronically early decline of expression of Hox genes is strongly correlated with the peculiar trait of the fibula in the avian hindlimb, since in the other species examined, expression of those genes continued after the onset of cartilage formation. This is morphological phenotype-related because the early disappearance was not seen in the chick forelimb. Our results suggest that temporal change of the Hox code governs diversification in morphology of homologous structures among related species. PMID:22708793

Kamiyama, Namiko; Seki, Ryohei; Yokoyama, Hitoshi; Tamura, Koji

2012-06-18

235

Hepatic osteodystrophy complicated with bone fracture in early infants with biliary atresia.  

PubMed

Biliary atresia (BA) is one of the major hepatobiliary abnormalities in infants and one of the causes of hepatic osteodystrophy. Bone disease may be caused by the malabsorption of calcium and magnesium by vitamin D in hepatobiliary diseases in which bile flow into the intestines is deficient or absent. Bone fracture before Kasai hepatic portoenterostomy or within one month after the procedure in an infant with BA is very rare. We herein report two infants: one infant with BA who initially presented with a bone fracture before Kasai hepatic portoenterostomy, and the other at 4 wk after Kasai hepatic portoenterostomy, and also provide a review of the literature. Moreover, we conclude that clinicians should consider BA in infants with bone fracture during early infancy. PMID:23293713

Okada, Tadao; Honda, Shohei; Miyagi, Hisayuki; Minato, Masashi; Taketomi, Akinobu

2012-10-27

236

Hepatic osteodystrophy complicated with bone fracture in early infants with biliary atresia  

PubMed Central

Biliary atresia (BA) is one of the major hepatobiliary abnormalities in infants and one of the causes of hepatic osteodystrophy. Bone disease may be caused by the malabsorption of calcium and magnesium by vitamin D in hepatobiliary diseases in which bile flow into the intestines is deficient or absent. Bone fracture before Kasai hepatic portoenterostomy or within one month after the procedure in an infant with BA is very rare. We herein report two infants: one infant with BA who initially presented with a bone fracture before Kasai hepatic portoenterostomy, and the other at 4 wk after Kasai hepatic portoenterostomy, and also provide a review of the literature. Moreover, we conclude that clinicians should consider BA in infants with bone fracture during early infancy.

Okada, Tadao; Honda, Shohei; Miyagi, Hisayuki; Minato, Masashi; Taketomi, Akinobu

2012-01-01

237

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

NASA Astrophysics Data System (ADS)

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-Núñez, A.; Pérez-Meza, M.

2012-10-01

238

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

239

Bones  

MedlinePLUS

Sections Bone, Joint, and Muscle Disorders Chapters Biology of the Musculoskeletal System Bones Bone, although strong, is a constantly changing tissue that has several functions. Bones serve as rigid structures to ...

240

Influence of early qualitative feed restriction and environmental temperature on long bone development of broiler chickens  

Microsoft Academic Search

This investigation was carried out to study the influence of early qualitative feed restriction and environmental rearing temperature on long bone development in broiler. Energy and protein restriction reduced femur width and humerus weight, but did not affect tibia parameters. Broilers kept at cold environmental temperature showed reduced femur, tibia and humerus length and tibia weight, but the calculated density

L. D. G. Bruno; B. C. Luquetti; R. L. Furlan; M. Macari

2007-01-01

241

Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children  

Microsoft Academic Search

Adenovirus infection remains an important cause of mortality after bone marrow transplantation (BMT). Currently no efficient antiviral treatment is known. Thus, testing new modalities of early diagnosis and treatment is a crucial objective. Adenovirus infection is defined by the combination of symptoms and the isolation of virus from the source of clinical symptoms. The involvement of two or more organs

F Legrand; D Berrebi; N Houhou; F Freymuth; A Faye; M Duval; JF Mougenot; M Peuchmaur; E Vilmer

2001-01-01

242

Epidermoids and dermoids of the calvarian bones in early childhood: Their behaviour in the growing skull  

Microsoft Academic Search

Summary Thirteen out of 25 cystic lesions of the infantile skull, radiographically classified as epidermoids or dermoids of the calvarian bones, disappeared spontaneously during early childhood. A further six lesions showed involution. In all, 19\\/25 lesions were involutive. In no case did we find an enlargement which could be attributed with certainly, to growth after the age of 3 years.

W. Holthusen; M. A. Lassrich; C. Steiner

1983-01-01

243

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

SciTech Connect

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

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

2006-01-01

244

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

2012-04-17

245

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

246

Circulating Bone Marrow Cells Can Contribute to Neointimal Formation  

Microsoft Academic Search

To examine the source of smooth muscle-like cells during vascular healing, C57BL\\/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 106 nucleated bone marrow cells from congenic (Ly 5.1) male donors. Successful repopulation (88.4 ± 4.9%) by donor marrow was demonstrated in the female mice by flow cytometry with FITC-conjugated A20.1\\/Ly 5.1 monoclonal antibody after 4

Chih-lu Han; Gordon R. Campbell; Julie H. Campbell

2001-01-01

247

Bone formation: The rules for fabricating a composite ceramic  

SciTech Connect

Bone, teeth and shells are complex composite ceramics which are fabricated at low temperature by living organisms. The detailed understanding of this fabrication process is required if we are to attempt to mimic this low temperature assembly process. The guiding principles and major components are outlined with the intent of establishing non-vital fabrication schemes to form a complex composite ceramic consisting of an organix matrix inorganic crystalline phase. 19 refs.

Caplan, A.I. (Case Western Reserve Univ., Cleveland, OH (USA))

1990-01-01

248

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

Microsoft Academic Search

Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional\\u000a molecules. In this study, we investigated the capacity of Straumann® Bone Ceramic coated with Straumann® Emdogain, a clinical\\u000a preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs)\\u000a including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts

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

249

Expression of growth hormone receptor by immunocytochemistry in rat molar root formation and alveolar bone remodeling  

Microsoft Academic Search

Growth hormone (GH) may regulate tooth formation and bone remodeling associated with tooth eruption. This study reports the distribution of growth hormone receptor\\/binding protein in developing rat molars and adjacent alveolar bone by immunocytochemistry using well-characterized anti-growth hormone receptor monoclonal antibodies. These tissues represent an excellent model for studying the ontogenic changes that occur in odontogenic and osteogenic cells, as

Chayvis Z. Zhang; W. G. Young; H. Li; A. M. Clayden; J. Garcia-Aragon; M. J. Waters

1992-01-01

250

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

251

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes  

Microsoft Academic Search

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from

E. H. Burger; J. S. van de Gevel; J. C. Gribnau; C. W. Thesingh; R. van Furth

1982-01-01

252

The early martian evolution—Constraints from basin formation ages  

NASA Astrophysics Data System (ADS)

Impact basin formation ages give insight into the early evolution of a planet. The martian basins Hellas, Isidis and Argyre provide an important time-marker for the cessation of the magnetic dynamo and the crustal thickness distribution, both established before 4 Ga ago. No martian surfaces are older than 4.15 Ga based on crater count statistics, and all are younger than the oldest lunar ones. I show that the heavy bombardment period on the Moon and Mars evolved similarly, but endogenic processes have removed the oldest martian basin record. The basin-forming projectile population appears to be different from the impactor population observed today in the inner Solar System. It is yet uncertain whether the heavy bombardment period is cataclysmic or characterized by the decaying flux of planetary formation.

Werner, S. C.

2008-05-01

253

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

254

Research on the early planet formation stages with IPE  

NASA Astrophysics Data System (ADS)

The early stages of planet formation are characterized by growth of fractal aggregates, starting from (sub-)micrometer-sized grains to (fractal) aggregates of roughly mm size. In the last 20 years a number of experiments on the behaviour and growth mechanisms of aggregates has been carried out. Laboratory experiments are limited due to sedimentation (e.g. Heim and Blum 1998, Wurm et al 2001). Previous long-term microgravity experiments CODAG (Blum et al 2000) and CODAG-SRE (Krause and Blum 2004) were mainly limited by the diffusion of particles, a fact which IPE tries to overcome by means of a particle trap. We present how IPE will help to extend these experimental boundaries and how we plan to utilize IPE. Finally we outline the expectations on the facility from a planet formation point of view in the domain of the mutual interactions, evolution, growth and morphology of fractal aggregates.

Ingo von Borstel, Olaf; Blum, Jurgen; Schraepler, Rainer

255

CCAAT/ENHANCER BINDING PROTEIN HOMOLOGOUS PROTEIN (CHOP) DECREASES BONE FORMATION AND CAUSES OSTEOPENIA  

PubMed Central

CCAAT enhancer binding protein (C/EBP) homologous protein (CHOP), is a member of the C/EBP family of nuclear proteins and plays a role in osteoblastic and adipocytic cell differentiation. CHOP is necessary for normal bone formation, but the consequences of its overexpression in vivo are not known. To investigate the direct actions of CHOP on bone remodeling in vivo, we generated transgenic mice overexpressing CHOP under the control of the human osteocalcin promoter. CHOP transgenics exhibited normal weight and reduced bone mineral density. Static and dynamic femoral bone histomorphometry revealed that CHOP overexpression caused reduced trabecular bone volume, secondary to decreased bone formation rates. One of 2 lines displayed a decrease in the number of osteoblasts, but in vivo bromodeoxyuridine labeling demonstrated that CHOP overexpression did not have an effect on osteoblastic cell replication. The decreased osteoblast cell number was accounted by an increase in apoptosis, as determined by DNA fragmentation measured by transferase-mediated digoxigenin-deoxyuridine triphosphate (dUTP) in situ nick-end labeling (TUNEL) reaction. In conclusion, transgenic mice overexpressing CHOP in the bone microenvironment have impaired osteoblastic function leading to osteopenia.

Pereira, Renata C.; Stadmeyer, Lisa E.; Smith, Deanna L.; Rydziel, Sheila; Canalis, Ernesto

2007-01-01

256

Acute effects of Solanum malacoxylon on bone formation rates in growing rats.  

PubMed

The plant Solanum malacoxylon is responsible for a syndrome of hypercalcemia, soft tissue mineralization, and progressive wasting in South American cattle known as enteque seco or espichamento. There is evidence that a glycoside of 1,25-dihydroxycholecalciferol is the active principle in the plant. The basis for the hyperostosis seen in the disease is unclear. To study the acute effects on bone formation rates, 8-week-old rats were given an aqueous extract equivalent to 250 or 1000 mg of Solanum daily per os for 7 days. Bones were labeled by injection of fluochrome 2 days before the start of treatment and 2 days prior to sacrifice. Morphometric evaluation of undecalcified sections of caudal vertebrae revealed an increased amount of trabecular bone in both Solanum treated groups with no difference due to dose level. This was associated with an increase in the bone apposition rate on trabecular surfaces. No differences were found in the amount of osteoid seam width. Periosteal apposition rate and endochondral bone formation were also measured and no significant differences found. The findings indicate that acute stimulation of cell level bone formation on trabecular surfaces may play a role in the hyperostosis seen in the naturally occurring condition. PMID:116737

Norrdin, R W; de Barros, C S; Queille, M L; Carré, M; Miravet, L

1979-11-01

257

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

SciTech Connect

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

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

1988-03-01

258

Predicting the external formation of callus tissues in oblique bone fractures: idealised and clinical case studies.  

PubMed

It is proposed that the external asymmetric formation of callus tissues that forms naturally about an oblique bone fracture can be predicted computationally. We present an analysis of callus formation for two cases of bone fracture healing: idealised and subject-specific oblique bone fractures. Plane strain finite element (FE) models of the oblique fractures were generated to calculate the compressive strain field experienced by the immature callus tissues due to interfragmentary motion. The external formations of the calluses were phenomenologically simulated using an optimisation style algorithm that iteratively removes tissue that experiences low strains from a large domain. The resultant simulated spatial formation of the healing tissues for the two bone fracture cases showed that the calluses tended to form at an angle equivalent to the angle of the oblique fracture line. The computational results qualitatively correlated with the callus formations found in vivo. Consequently, the proposed methods show potential as a means of predicting callus formation in pre-clinical testing. PMID:23306603

Comiskey, D; Macdonald, B J; McCartney, W T; Synnott, K; O'Byrne, J

2013-01-10

259

Relationship between bone formation markers bone alkaline phosphatase, osteocalcin and amino-terminal propeptide of type I collagen and bone mineral density in elderly men. Preliminary results.  

PubMed

Bone remodeling is altered in all metabolic bone diseases, especially in post-menopausal women and in the elderly. Predicting changes in bone mineral density (BMD) is useful to manage the progression of such diseases and to potentially provide interventions in reducing fracture risk. Continuous bone formation and resorption processes can be monitored by measuring biochemical markers of bone turnover (BTMs) and a relationship between BMD and BTMs has been known for long. The aim of this study was to evaluate the relationship between BMD and serum BTMs bone alkaline phosphatase (BAP), osteocalcin and amino-terminal propeptide of type I collegen (PINP) in elderly (>65 years) men. We prospectively studied 18 elderly men (median age=69, range=65-77 years) with no history of fractures, angina, stroke, myocardial infarction or diabetes mellitus. Patients who had undergone corticosteroid, calcitonin, androgen or bisphosphonate therapy were excluded from the study, as well as those who were vitamin D and calcium supplementation users. All the patients underwent lumbar-spine (L2-L4) dual-energy x-ray absorbtiometry and BMD, BAP, osteocalcin and PINP measurements. The mean BMD and body mass index (BMI) were 0.963±0.04 g/cm(2) and 24.4±1.2 kg/m(2), respectively. BAP, osteocalcin and PINP were 27.8±11.3 U/l, 25.6±7.1 ng/ml and 36.0±7.5 ng/ml, respectively. No correlation was found between BMD and BAP (R=-0.28, p=0.25), osteocalcin (R=-0.18, p=0.48) and PINP (R=-0.21, p=0.39), nor between BMI and both age (R=0.05, p=0.83) and BMD (R=0.10, p=0.67). In conclusion, we did not find any relationship between bone formation markers BAP, osteocalcin and PINP and bone density. Thus, our preliminary data suggest that BTMs are not useful in monitoring the bone mineral status of elderly men. PMID:23160690

Lumachi, Franco; Orlando, Rocco; Fallo, Francesco; Basso, Stefano M M

260

Bone formation and implant degradation of coralline porous ceramics placed in bone and ectopic sites  

Microsoft Academic Search

Purpose: This study was undertaken to determine the resorption rate of porous ceramic implants. The hypothesis was that implants placed in soft tissues would degrade more rapidly than implants placed in bone.Materials and Methods: To test this hypothesis, implants were manufactured by applying a thin coating of hydroxylapatite onto an interconnected, porous calcium carbonate substrate. Control implants were made entirely

Sharon Pollick; Edwin C Shors; Ralph E Holmes; Richard A Kraut

1995-01-01

261

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

PubMed

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

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

2011-12-09

262

Osseous metaplasia with mature bone formation of the thyroid gland: Three case reports  

PubMed Central

Nodular hyperplasia (nodular or multinodular goiter) is the most common form of thyroid disease. These nodules may undergo secondary changes in the form of hemorrhages, calcification and cystic degeneration. However, osseous metaplasia with mature bone formation rarely occurs. The present study reports the cases of three female patients with thyroid nodules diagnosed as nodular hyperplasia with osseous metaplasia and mature bone formation. The patients underwent right lobectomy, near total thyroidectomy and total thyroidectomy, respectively. The clinical course of the patients following resection were unremarkable.

CHUN, JI-SUN; HONG, RAN; KIM, JUNG-A

2013-01-01

263

Bone response to orthodontic loading of endosseous implants in the rabbit calvaria: early continuous distalizing forces.  

PubMed

The purpose of this experimental study was to evaluate the effect of early orthodontic loading on the stability and bone-implant interface of titanium implants in a rabbit model. Twenty-four short threaded titanium fixtures were inserted in the calvarial mid-sagittal suture of 10 rabbits. Two weeks following insertion, 20 implants (test group) were subjected to continuous distalization forces of 150 g for a period of 8 weeks. The remaining four implants (control group) were left unloaded for the same follow-up interval. Clinically, all implants except for one test fixture were stable, and exhibited no mobility or displacement throughout the experimental loading period. Histologically, all stable implants were well-integrated into bone. No differences could be found between the pressure and tension surfaces of the test implants relative to bone quality and density within a range of 1000 microns from the fixture surface. Similarly, qualitative differences were not observed between the apical and coronal portions of test fixtures. Morphometrically, a mean percentage bone-to-implant contact of 76.00 +/- 18.73 per cent was found at the test pressure sides, 75.00 +/- 11.54 per cent at the test tension sides, and 68.00 +/- 15.55 per cent at the control unloaded surfaces. No statistically significant differences in the percentage of bone-to-metal contact length fraction were found between test pressure surfaces, test tension surfaces, and unloaded control surfaces. Marginal bone resorption around the implant collar or immediately beneath it was found in roughly the same percentage of analysed sites in the test and control fixtures. In contrast, slight bone apposition was demonstrated at the implant collar of the test pressure surfaces, while no apposition or resorption were observed in the test tension zones. This study suggests that short endosseous implants can be used as anchoring units for orthodontic tooth movement early in the post-insertion healing period. PMID:10407532

Majzoub, Z; Finotti, M; Miotti, F; Giardino, R; Aldini, N N; Cordioli, G

1999-06-01

264

Spatiotemporal Pattern Formation in Early Development: A Review of Primitive Streak Formation and Somitogenesis  

Microsoft Academic Search

\\u000a The basic body plan of a number of vertebrates results from two processes that occur early in the development of the blastoderm:\\u000a large scale rearrangements of tissue via a process called gastrulation, and axial subdivision of tissue in a process called\\u000a somitogenesis. The first step of gastrulation in avians is formation of the primitive streak, which marks the first clear

S. Schnell; K. J. Painter; P. K. Maini; H. G. Othmer

265

Beneath the Minerals, a Layer of Round Lipid Particles Was Identified to Mediate Collagen Calcification in Compact Bone Formation  

Microsoft Academic Search

Astronauts lose 1–2% of their bone minerals per month during space flights. A systematic search for a countermeasure relies on a good understanding of the mechanism of bone formation at the molecular level. How collagen fibers, the dominant matrix protein in bones, are mineralized remains mysterious. Atomic force microscopy was carried out, in combination with immunostaining and Western blotting, on

Shaohua Xu; Jianqing J. Yu

2006-01-01

266

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

267

Semi-analytic galaxy formation in early dark energy cosmologies  

NASA Astrophysics Data System (ADS)

We study the impact of early dark energy (EDE) cosmologies on galaxy properties by coupling high-resolution numerical simulations with semi-analytic modelling (SAM) of galaxy formation and evolution. EDE models are characterized by a non-vanishing high-redshift contribution of dark energy, producing an earlier growth of structures and a modification of large-scale structure evolution. They can be viewed as typical representatives of non-standard dark energy models in which only the expansion history is modified, and hence the impact on galaxy formation is indirect. We show that in EDE cosmologies the predicted space density of galaxies is enhanced at all scales with respect to the standard ? cold dark matter (?CDM ) scenario, and the corresponding cosmic star formation history and stellar mass density are increased at high redshift. We compare these results with a set of theoretical predictions obtained with alternative SAMs applied to our reference ?CDM simulation, yielding a rough measure of the systematic uncertainty of the models. We find that the modifications in galaxy properties induced by EDE cosmologies are of the same order of magnitude as intra-SAM variations for a standard ?CDM realization (unless rather extreme EDE models are considered), suggesting that it is difficult to use such predictions alone to disentangle between different cosmological scenarios. However, when independent information on the underlying properties of host dark matter haloes is included, the SAM predictions on galaxy bias may provide important clues to the expansion history and the equation-of-state evolution.

Fontanot, Fabio; Springel, Volker; Angulo, Raul E.; Henriques, Bruno

2012-11-01

268

Is bone formation induced by high-frequency mechanical signals modulated by muscle activity?  

PubMed

Bone formation and resorption are sensitive to both external loads arising from gravitational loading as well to internal loads generated by muscular activity. The question as to which of the two sources provides the dominant stimulus for bone homeostasis and new bone accretion is arguably tied to the specific type of activity and anatomical site but it is often assumed that, because of their purportedly greater magnitude, muscle loads modulate changes in bone morphology. High-frequency mechanical signals may provide benefits at low- (<1g) and high- (>1g) acceleration magnitudes. While the mechanisms by which cells perceive high-frequency signals are largely unknown, higher magnitude vibrations can cause large muscle loads and may therefore be sensed by pathways similar to those associated with exercise. Here, we review experimental data to examine whether vibrations applied at very low magnitudes may be sensed directly by transmittance of the signal through the skeleton or whether muscle activity modulates, and perhaps amplifies, the externally applied mechanical stimulus. Current data indicate that the anabolic and anti-catabolic effects of whole body vibrations on the skeleton are unlikely to require muscular activity to become effective. Even high-frequency signals that induce bone matrix deformations of far less than five microstrain can promote bone formation in the absence of muscular activity. This independence of cells on large strains suggests that mechanical interventions can be designed that are both safe and effective. PMID:20190375

Judex, S; Rubin, C T

2010-03-01

269

The prenyl group contributes to activities of phytoestrogen 8-prenynaringenin in enhancing bone formation and inhibiting bone resorption in vitro.  

PubMed

Previous studies have found that 8-prenylflavonoids have a higher osteogenic activity than do flavonoids, which suggested that the 8-prenyl group may play an active role in bone-protective properties. To address this hypothesis, activities of 8-prenylnaringenin (PNG) and naringenin (NG) in osteoblast and osteoclast differentiation and function were compared in vitro. PNG was found to have a stronger ability than NG to improve osteoblast differentiation and osteogenic function in cultured rat calvarial osteoblasts, as demonstrated by levels of alkaline phosphatase activity, osteocalcin, calcium deposition, and the number and area of mineralized bone nodules, as well as mRNA expression of osteogenesis-related genes Bmp-2, OSX, and Runx-2. In addition, although expression of osteoclastogenic inducer receptor activator of nuclear factor kappa-B ligand (RANKL) was not affected, that of osteoclastogenesis inhibitor osteoprotegerin (OPG) and consequently the OPG/RANKL ratio were increased, more potently by PNG than NG. PNG was also found to have a higher potency than NG in inhibiting the osteoclast formation in rabbit bone marrow cells and their resorptive activity, as revealed by lower numbers of osteoclasts formed, lower numbers and areas of bone resorption pits, and lower mRNA expression levels of tartrate-resistant acid phosphatase and cathepsin K. Furthermore, PNG induced apoptosis of mature osteoclasts at a higher degree and at an earlier time than did NG. These results indicate that the 8-prenyl group plays an important role and contributes to the higher bone-protective activity of PNG in comparison with NG. PMID:23389955

Ming, Lei-Guo; Lv, Xiang; Ma, Xiao-Ni; Ge, Bao-Feng; Zhen, Ping; Song, Peng; Zhou, Jian; Ma, Hui-Ping; Xian, Cory J; Chen, Ke-Ming

2013-02-06

270

[Bone metabolic marker for osteoporosis].  

PubMed

The purposes hypothesized for the determination of bone metabolic markers, among which we can measure serum BAP, NTX, TRAP-5b or urinary NTX, DPD, CTX in routine clinical practice, are to predict the rate of bone loss and the resultant fracture risk, and to estimate bone quality. The higher value of bone markers, which might reflect high turnover bone disease, allows us to discriminate those who require early introduction of drug therapy such as bisphosphonate, and raloxifene. Furthermore, early reduction of bone resorption markers, but not bone formation markers, possibly 3-6 month after initiation of bone anti-resorptive drugs, enables us to predict bone gain thereafter. Among various bone resorption markers, TRAP-5b might be the best in that it is not susceptible to between-day variation, day-to-day variation, and renal dysfunction resulting from chronic kidney disease which often occurs in osteoporosis-prone elderly women. PMID:19432111

Shidara, Kaori; Inaba, Masaaki

2009-05-01

271

In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes  

PubMed Central

The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co- cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes.

1982-01-01

272

Inhibitory effect of menaquinone-7 (vitamin K2) on osteoclast-like cell formation and osteoclastic bone resorption in rat bone tissues in vitro  

Microsoft Academic Search

The effect of menaquinone-7 (MK-7; vitamin K2) on oateoclast-like cell formation and osteoclastic bone resorption in rat femoral tissues in vitro was investigated. The bone marrow cells were cultured for 7 days in a a-minimal essential medium (a-MEM) containing a well-known bone resorbing agent [parathyroid hormone (1–34) (PTH) or prostaglandin E2 (PGE2)] with an effective concentration. Osteoclast-like cells were estimated

Masayoshi Yamaguchi; Zhong Jie Ma

2001-01-01

273

Bone Formation Zones in Heterotopic Ossifications: Histologic Findings and Increased Expression of Bone Morphogenetic Protein 2 and Transforming Growth Factors ß2 and ß3  

Microsoft Academic Search

Heterotopic ossifications (HOs) formed after total endoprosthetic replacement of the hip joint were collected during revision\\u000a surgery (n = 7). Tissues collected during regular hip arthroplasty (n = 12) were used as reference. Histomorphometric analysis was performed for assessment of bone formation activity in HOs and\\u000a reference bone. HOs were dissected with histological guidance into three zones: formed bone, zone

A. Toom; A. Arend; D. Gunnarsson; R. Ulfsparre; S. Suutre; T. Haviko; G. Selstam

2007-01-01

274

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.

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

2012-01-01

275

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

NASA Astrophysics Data System (ADS)

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

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

2006-08-01

276

Bone Metastasis from Primary Hepatocellular Carcinoma: Characteristics of Soft Tissue Formation  

PubMed Central

Purpose To assess the characteristics of bone metastasis from hepatocellular carcinoma and the radiation field arrangement based on imaging studies. Materials and Methods Fifty-three patients (84 lesions) with bone metastasis from a primary hepatocellular carcinoma completed palliative radiation therapy. All patients underwent one of following imaging studies prior to the initiation of radiation therapy: a bone scan, computed tomography or magnetic resonance imaging. The median radiation dose was 30 Gy (7~40 Gy). We evaluated retrospectively the presence of soft tissue formation and the adjustment of the radiation field based on the imaging studies. Results Soft tissue formation at the site of bony disease was identified from either a CT/MRI scan (41 lesions) or from a symptomatic palpable mass (5 lesions). The adjustment of the radiation field size based on a bone scan was necessary for 31 of 41 soft tissue forming lesions (75.6%), after a review of the CT/MRI scan. The median survival from the initial indication of a hepatoma diagnosis was 8 months (2 to 71 months), with a 2-year survival rate of 38.6%. The median survival from the detection of a bone metastasis was 5 months (1 to 38 months) and the 1-year overall survival rate was 8.7%. Conclusion It was again identified that bone metastasis from a primary hepatocellular carcinoma is accompanied by soft tissue formation. From this finding, an adjustment of the radiation field size based on imaging studies is required. It is advisable to obtain a CT or MRI scan of suspected bone metastasis for better tumor volume coverage prior to the initiation of radiation therapy.

Kim, Sangwon; Wang, Heejung; Cho, Sungwon; Oh, Young-Taek; Kang, Seung-Hee; Yang, Juno

2007-01-01

277

Occurrence of new bone-like tissue formation in uremic tumoral calcinosis.  

PubMed

A 55-year-old woman who had been on hemodialysis for 5years was admitted for evaluation of a hard mass in the right hip region. Her serum calcium (Ca)-phosphate (P) product was elevated. Radiographs showed periarticular calcified masses in the soft tissues around both hips and shoulders, which were characteristic of uremic tumoral calcinosis (UTC). Biopsy specimens were obtained from both right hip mass and the right iliac crest. Histological examination of hip mass revealed bone-like tissue with marrow, as well as calcified material. The bone-like tissue was categorized as heterotopic ossification (HO), because it had been formed inside soft tissue where bone-like tissue does not normally exist. Histological analysis of HO showed the formation of cancellous bone-like tissue. Woven mineralized bone-like tissue was predominant over lamellar bone-like tissue. High bone turnover combined with osteitis fibrosa-like lesion was diagnosed because of an increase of the fibrous volume, as well as clear double tetracycline labeling. Near a site of HO, numerous ALP- and Runx2-positive cuboidal osteoblast-like cells and TRAP- and cathepsin K-positive multinucleated osteoclast-like cells were noted. Histomorphometric analysis of the right iliac crest revealed osteitis fibrosa. This is the first report of HO in a patient with UTC. After parathyroidectomy, the patient's Ca-P imbalance was corrected and UTC subsided. Although the mechanism by which new bone-like tissue formation arises in the soft tissues has not yet been determined, secondary hyperparathyroidism may have contributed to the progression of UTC in this patient. PMID:23142362

Hiramatsu, Rikako; Ubara, Yoshifumi; Hayami, Noriko; Yamanouchi, Masayuki; Hasegawa, Eiko; Sumida, Keiichi; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Amizuka, Norio; Takaichi, Kenmei

2012-11-06

278

Spontaneous bone formation on the maxillary sinus floor in association with an extraction socket  

Microsoft Academic Search

A case is reported of spontaneous bone formation on the maxillary sinus floor associated with the extraction socket of a maxillary impacted tooth. An impacted maxillary second premolar of a 20-year-old male had been pushed into the maxillary sinus during surgical extraction. The tooth was removed using the sinus elevation technique. After 5 months of healing, the space between the

Y.-S. Jung; S.-W. Chung; W. Nam; I.-H. Cho; I.-H. Cha; H.-S. Park

2007-01-01

279

Autologous fat grafts placed around temporomandibular joint total joint prostheses to prevent heterotopic bone formation  

Microsoft Academic Search

This study evaluated 1) the efficacy of packing autologous fat grafts around temporomandibular joint (TMJ) total joint prosthetic reconstruc- tions to prevent fibrosis and heterotopic bone formation and 2) the ef- fects on postsurgical joint mobility and jaw function. One hundred fifteen patients (5 males and 110 females) underwent TMJ reconstruction with total joint prostheses and simultaneous fat grafts (88

Larry M. Wolford; Carlos A. Morales-Ryan; Patricia Garcia Morales; Daniel Serra Cassano

280

Effects of latency and rate on bone formation in a porcine mandibular distraction model  

Microsoft Academic Search

Purpose: Long treatment protocols currently limit the application of distraction osteogenesis (DO). The purpose of this study was to develop a porcine model for DO and to define the effects of latency and distraction rate on bone formation.Materials and Methods: Distractors were placed through submandibular incisions. For analysis of latency, mandibular osteotomies were distracted after 0 (n = 3) or

Maria J. Troulis; Julie Glowacki; David H. Perrott; Leonard B. Kaban

2000-01-01

281

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

Microsoft Academic Search

The rare earth element (REE) content of fossil bones was analyzed and compared with the degree of ancient pedogenic development and depositional environments from several locations in the Orellan Scenic Member of the Oligocene Brule Formation in Badlands National Park, South Dakota. Paleosols ranged from weakly developed Entisols to more strongly developed Inceptisols, all typical of fluvial environments and possible

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

2004-01-01

282

Diabetes Interferes with the Bone Formation by Affecting the Expression of Transcription Factors that Regulate Osteoblast Differentiation  

Microsoft Academic Search

Type 1 diabetes in humans has as one of its complications inadequate bone formation, resulting in osteopenia and de- layed fracture healing. To investigate the mechanisms by which diabetes affects bone formation, experiments were per- formed in a marrow ablation model. Mice were made diabetic by multiple low-dose streptozotocin treatment, and controls were treated with vehicle alone. Killing occurred 0,

HUAFEI LU; DOUGLAS KRAUT; LOUIS C. GERSTENFELD; DANA T. GRAVES

2003-01-01

283

Laboratory Investigations Bone Formation Zones in Heterotopic Ossifications: Histologic Findings and Increased Expression of Bone Morphogenetic Protein 2 and Transforming Growth Factors ß2 and ß3  

Microsoft Academic Search

Heterotopic ossifications (HOs) formed after total endoprosthetic replacement of the hip joint were collected during revision surgery (n = 7). Tissues col- lected during regular hip arthroplasty (n = 12) were used as reference. Histomorphometric analysis was per- formed for assessment of bone formation activity in HOs and reference bone. HOs were dissected with histological guidance into three zones: formed

A. Toom; A. Arend; D. Gunnarsson; R. Ulfsparre; S. Suutre; T. Haviko; G. Selstam

284

Marginal Zinc Deficiency in Pregnant Rats Impairs Bone Matrix Formation and Bone Mineralization in Their Neonates  

Microsoft Academic Search

Zinc (Zn) deficiency during pregnancy may result in a variety of defects in the offspring. We evaluated the influence of marginal\\u000a Zn deficiency during pregnancy on neonatal bone status. Nine-week-old male Sprague-Dawley rats were divided into two groups\\u000a and fed AIN-93G-based experimental diets containing 35 mg Zn\\/kg (Zn adequately supplied, N) or 7 mg Zn\\/kg (low level of Zn,\\u000a L) from 14-day

Masashi Nagata; Megumu Kayanoma; Takeshi Takahashi; Tetsuo Kaneko; Hiroshi Hara

2011-01-01

285

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

286

Regulation of Postnatal Trabecular Bone Formation by the Osteoblast Endothelin A Receptor  

PubMed Central

Endothelin-1 (ET-1) is a potent vasoconstrictor that also stimulates cells in the osteoblast lineage by binding to the endothelin A receptor (ETAR). ET-1 ligand is widely secreted, particularly by the vasculature. However, the contributions of ETAR signaling to adult bone homeostasis have not been defined. ETAR was inactivated in osteoblasts by crossing ETAR-floxed and osteocalcin-Cre mice. Histomorphometric analyses were performed on 4-, 8-, and 12-week-old osteoblast-targeted ETAR knockout (KO) and wild-type (WT) male and female mice. Tibial trabecular bone volume was significantly lower from 12 weeks in KO versus WT mice in both males and females. Bone-formation rate, osteoblast density, and in vitro osteoblast differentiation were reduced by targeted inactivation of ETAR. A separate longitudinal analysis was performed between 8 and 64 weeks to examine the effect of aging and castration on bone metabolism in ETAR KO mice. Hypogonadism did not change the rate of bone accrual in WT or KO females. However, eugonadal KO males had a significantly larger increase in tibial and femoral bone acquisition than WT mice. Male mice castrated at 8 weeks of age showed the reverse: KO mice had reduced rates of tibial and femoral BMD acquisition compared with WT mice. In vitro, ET-1 increased osteoblast proliferation, survival, and differentiation. Dihydrotestosterone also increased osteoblast differentiation using a mechanism distinct from the actions of ET-1. These results demonstrate that endothelin signaling in osteoblasts is an important regulator of postnatal trabecular bone remodeling and a modulator of androgen effects on bone. © 2011 American Society for Bone and Mineral Research

Clines, Gregory A; Mohammad, Khalid S; Grunda, Jessica M; Clines, Katrina L; Niewolna, Maria; McKenna, C Ryan; McKibbin, Christopher R; Yanagisawa, Masashi; Suva, Larry J; Chirgwin, John M; Guise, Theresa A

2011-01-01

287

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.  

PubMed

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation. PMID:23584739

Kim, Minsung; Jung, Won-Kyo; Kim, Geunhyung

2013-04-14

288

STAR FORMATION SIGNATURES IN OPTICALLY QUIESCENT EARLY-TYPE GALAXIES  

SciTech Connect

In recent years, an argument has been made that a high fraction of early-type galaxies (ETGs) in the local universe experience low levels ({approx_lt}1 M {sub sun} yr{sup -1}) of star formation (SF) that causes strong excess in UV flux, yet leaves the optical colors red. Many of these studies were based on Galaxy Evolution Explorer imaging of Sloan Digital Sky Survey (SDSS) galaxies (z {approx} 0.1), and were thus limited by its 5'' FWHM. Poor UV resolution left other possibilities for UV excess open, such as the old populations or an active galactic nucleus (AGN). Here, we study high-resolution far-ultraviolet HST/ACS images of optically quiescent early-type galaxies with strong UV excess. The new images show that three-quarters of these moderately massive ({approx}5 x 10{sup 10} M {sub sun}) ETGs shows clear evidence of extended SF, usually in form of wide or concentric UV rings, and in some cases, striking spiral arms. SDSS spectra probably miss these features due to small fiber size. UV-excess ETGs have on average less dust and larger UV sizes (D > 40 kpc) than other green-valley galaxies, which argues for an external origin for the gas that is driving the SF. Thus, most of these galaxies appear 'rejuvenated' (e.g., through minor gas-rich mergers or intergalactic medium accretion). For a smaller subset of the sample, the declining SF (from the original internal gas) cannot be ruled out. SF is rare in very massive early-types (M {sub *} > 10{sup 11} M {sub sun}), a possible consequence of AGN feedback. In addition to extended UV emission, many galaxies show a compact central source, which may be a weak, optically inconspicuous AGN.

Salim, Samir [Department of Astronomy, Indiana University, Bloomington, IN 47404 (United States); Rich, R. Michael, E-mail: salims@indiana.ed [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095 (United States)

2010-05-10

289

Planet Formation and Early Solar System heating: Recent advancements  

NASA Astrophysics Data System (ADS)

In a seminal review in 1991, Wood and Pellas laid out the basic characteristics of protoplanetary heating as preserved in the meteorite record and pointed out the strengths and drawbacks of the two plausible heat sources: 26Al and electromagnetic induction. A decade and a half later, considerable advances have been made, in our theoretical understanding of planet formation and its effect on protoplanetary heating. In addition, remarkable progress has been made in meteoritic studies, including geochronological measurements and the search for fossil remains of 26Al in various chondrites and achondrites. The case for 26Al heating of asteroids has become increasingly robust. Its decay product has been found in most classes of chondrites and some achondrites. Reasons as to why evidence for 26Al might be obscured in other achondrites have been suggested. The heat source appears capable of explaining the full range of temperature excursions of asteroids within the main belt. The process of accretion has been shown to be intrinsically related to the thermal evolution of a protoplanetary body, since the timescale of accretion is comparable to the half life of the heat source. Thus, discerning characteristics of the parent body like volume proportion of various petrologic types, thermal-model cooling rates and closure ages, have been shown to be a function of accretion rate. A study of 244Pu fission tracks and 40Ar-39Ar thermochronology of unshocked H chondrites seems to provide support to a layered onion shell parent body, where the outer layers cooled faster than the asteroidal interior. This fits the pattern of heating generated by 26Al, where the heat source is distributed uniformly per unit mass. Nebular homogeneity and detectable excesses of fossil 26Mg are necessary but not sufficient conditions for 26Al heating to be viable. It is critical for the heat source to be live at the time, and after, the formation of the planetary building blocks. Thus, the time, relative to CAI formation, at which accretion initiates, and the duration of the accretionary process strongly influence the efficacy of 26Al as a heat source. The oldest chondrule Pb-Pb dates measured are 4566.6 +/- 1.0 Myrs for Allende: this denotes a time interval of 0.6 +/- 1.2 Myrs between CAI and chondrule formation. If initiation of accretion is assumed to postdate formation of the oldest chondrules, time of initiation of accretion relative to CAI formation can be interpreted as the time difference between CAI and chondrule formation: thus, accretion can initiate between 0 to 1.8 Myrs after CAI formation. Recent accretional models produce Mars-sized ( ˜1027 g) planetary embryos in < 1 Myr. Runaway growth generates a bimodal size distribution with numerous ˜100 km bodies that accrete on a comparable timescale. Melting and metarmorphism in the asteroid belt is likely to have occurred if accretion initiates between 0 to 1.8 Myrs and if duration of accretion is of the order of a few Myrs. The issue of possible nebular heterogeneity of 26Al clouds its efficacy as a heat source. Recent work, on electromagnetic induction, suggests that electromagnetic induction could cause melting in asteroids: however, the input parameter sets for the models remain largely unconstrained. Thus, the issue, of whether electromagnetic induction could have been the protoplanetary heat source in the early Solar System, remains unresolved.

Ghosh, A.; Weidenschilling, S. J.; Amelin, Y.; McSween, H. Y.

2004-12-01

290

The influence of collagen and hyaluronan matrices on the delivery and bioactivity of bone morphogenetic protein-2 and ectopic bone formation.  

PubMed

Bone morphogenetic protein-2 (BMP-2) is known to enhance fracture healing when delivered via a bovine collagen sponge. However, collagen rapidly releases BMP-2 with a high burst phase that is followed by a low sustained phase. As a result, supra-physiological doses of BMP-2 are often required to successfully treat bone defects. High BMP-2 dosing can introduce serious side effects that include edema, bone overgrowth, cyst-like bone formation and significant inflammation. As the release behavior of BMP-2 carriers significantly affects the efficacy of fracture healing, we sought to compare the influence of two BMP-2 delivery matrices with contrasting release profiles on BMP-2 bioactivity and ectopic bone formation. We compared a thiol-modified hyaluronan (Glycosil™) hydrogel that exhibits a low burst followed by a sustained release of BMP-2 to a collagen sponge for the delivery of three different doses of BMP-2, the bioactivities of released BMP-2 and ectopic bone formation. Analysis of bone formation by micro-computed tomography revealed that low burst followed by sustained release of BMP-2 from a hyaluronan hydrogel induced up to 456% more bone compared to a BMP-2 dose-matched collagen sponge that has a high burst and sustained release. This study demonstrates that BMP-2 released with a low burst followed by a sustained release of BMP-2 is more desirable for bone formation. This highlights the therapeutic potential of hydrogels, particularly hyaluronan-based, for the delivery of BMP-2 for the treatment of bone defects and may help abrogate the adverse clinical effects associated with high dose growth factor use. PMID:23871940

Bhakta, Gajadhar; Lim, Zophia X H; Rai, Bina; Lin, Tingxuan; Hui, James H; Prestwich, Glenn D; van Wijnen, Andre J; Nurcombe, Victor; Cool, Simon M

2013-07-19

291

Erythropoietin augments bone formation in a rabbit posterolateral spinal fusion model.  

PubMed

We tested the hypothesis that erythropoietin (EPO) enhances bone formation after posterolateral spinal fusion (PLF) in a rabbit model. Thirty-four adult rabbits underwent posterolateral intertransverse arthrodesis at the L5-L6 level using 2.0 g autograft per side. The animals were randomly divided into two groups receiving subcutaneous daily injections of either EPO or saline for 20 days. Treatment commenced 2 days preoperatively. Hemoglobin was monitored at baseline and 2, 4, and 6 weeks after fusion surgery. After euthanasia 6 weeks postoperatively, manual palpation, radiographic, and histomorphometric examinations were performed. Bone volume of the fusion mass was estimated by CT after 6 weeks. EPO increased bone fusion volume to 3.85 ccm (3.66-4.05) compared with 3.26 ccm (2.97-3.55) in the control group (p<0.01). EPO treatment improved vascularization of the fusion mass and increased hemoglobin levels (p<0.01). Fusion rate tended to be higher in the EPO group based on manual palpation, CT, and radiographic examinations. For the first time EPO has shown to augment bone formation after autograft PLF in a rabbit model. Increased vascularization provides a partial explanation for the efficacy of EPO as a bone autograft enhancer. PMID:22144136

Rölfing, Jan Hendrik Duedal; Bendtsen, Michael; Jensen, Jonas; Stiehler, Maik; Foldager, Casper Bindzus; Hellfritzsch, Michel Bach; Bünger, Cody

2011-12-05

292

The influence of bone formation on anchoring percutaneous devices with titanium fibre mesh flanges.  

PubMed

For man-made percutaneous devices (PD), it is known that anchoring will improve the clinical success. Previously, our Department has designed PDs that use a sheet of titanium (Ti) fibre mesh for anchoring. In nature, a very successful natural PD occurs, namely the tooth. Teeth are anchored in the alveolar bone. In the current study, we evaluated whether a sheet of (ectopic) bone can be made, and be used to anchor a skin-penetrating device. Using available tissue engineering techniques, sheets of Ti fibre mesh were loaded with osteoblast-like cells. These sheets, and non-loaded controls, were placed subcutaneously in 20 syngeneic rats. After four weeks 10 rats were sacrificed, and tissues were prepared for histology. On the other 10 rats, a percutaneous Ti bar was screwed. These rats were evaluated clinically up to eight weeks. Finally, also their tissues were prepared for histology. The results showed, that bone formation was only established in one cell-loaded implant, of the four-week group. Clinical evaluation, and the histomorphometrical data, showed no differences between cell-loaded and unloaded samples. We concluded that the combination of Ti mesh with rat bone marrow cells was not able to generate bone formation after subcutaneous implantation predictably. Thus, our original aim could not be met. On the other hand, our results did confirm the biocompatible behaviour of a PD equipped with a Ti fibre mesh anchoring flange. PMID:15387417

Shalabi, M M; Walboomers, X F; Jansen, J A

2004-07-01

293

The role of intracellular calcium phosphate in osteoblast-mediated bone apatite formation  

PubMed Central

Mineralization is a ubiquitous process in the animal kingdom and is fundamental to human development and health. Dysfunctional or aberrant mineralization leads to a variety of medical problems, and so an understanding of these processes is essential to their mitigation. Osteoblasts create the nano-composite structure of bone by secreting a collagenous extracellular matrix (ECM) on which apatite crystals subsequently form. However, despite their requisite function in building bone and decades of observations describing intracellular calcium phosphate, the precise role osteoblasts play in mediating bone apatite formation remains largely unknown. To better understand the relationship between intracellular and extracellular mineralization, we combined a sample-preparation method that simultaneously preserved mineral, ions, and ECM with nano-analytical electron microscopy techniques to examine osteoblasts in an in vitro model of bone formation. We identified calcium phosphate both within osteoblast mitochondrial granules and intracellular vesicles that transported material to the ECM. Moreover, we observed calcium-containing vesicles conjoining mitochondria, which also contained calcium, suggesting a storage and transport mechanism. Our observations further highlight the important relationship between intracellular calcium phosphate in osteoblasts and their role in mineralizing the ECM. These observations may have important implications in deciphering both how normal bone forms and in understanding pathological mineralization.

Boonrungsiman, Suwimon; Gentleman, Eileen; Carzaniga, Raffaella; Evans, Nicholas D.; McComb, David W.; Porter, Alexandra E.; Stevens, Molly M.

2012-01-01

294

The sealed osteons of cortical diaphyseal bone. Early observations revisited with scanning electron microscopy.  

PubMed

The frequency, structure, mode of formation and significance of sealed osteons remain unsettled. Sealed osteons have been reported as an unusual finding in the cortical bone of experimental animals: we extended the observation to human cortical bone studied with SEM. Tibial bone specimens from three patients who sustained a traumatic below-the-knee amputation were used in the study. The observed total mean density of osteons was 19.25/mm(2) and the percentage of sealed and partially sealed osteons was 4.2% and 1.7% respectively. The material sealing the central canal showed an X-ray microanalysis spectrum with the same Ca/P ratio as the peripheral lamellae and a lower carbon signal. The morphology suggested a reactivation of bone apposition triggered by exclusion of the occluded canal from blood flow rather than a physiological evolution of the closing process of secondary osteons. This presupposes collapse and degeneration of the central vessel before the osteoblasts resting on the inner surface of the canal could start to lay down new bone matrix. This explanation is consistent with a dynamic model of intracortical blood flow. PMID:21234993

Congiu, Terenzio; Pazzaglia, Ugo E

2010-12-03

295

Transgenic Overexpression of Ephrin B1 in Bone Cells Promotes Bone Formation and an Anabolic Response to Mechanical Loading in Mice  

PubMed Central

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-Tgefnb1). Col3.6-Tgefnb1 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-Tgefnb1 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-Tgefnb1 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-Tgefnb1 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.

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

2013-01-01

296

Skeletal repair by in situ formation of the mineral phase of bone  

SciTech Connect

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 of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs. 33 refs., 6 figs., 1 tab.

Constantz, B.R.; Ison, I.C.; Fulmer, M.T.; Poser, R.D.; Smith, S.T.; VanWagoner, M. [Norian Corporation, Cupertino, CA (United States); Ross, J. [Stanford Univ., Stanford, CA (United States); Goldstein, S.A. [Univ. of Michigan, Ann Arbor, MI (United States); Jupiter, J.B.; Rosenthal, D.I. [Massachusetts General Hospital, Boston, MA (United States)

1995-03-24

297

Pyk2 regulates megakaryocyte-induced increases in osteoblast number and bone formation.  

PubMed

Preclinical and clinical evidence from megakaryocyte (MK)-related diseases suggests 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 because of 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

2013-06-01

298

BMP-2 gene-fibronectin-apatite composite layer enhances bone formation  

PubMed Central

Background Safe and efficient gene transfer systems are needed for tissue engineering. We have developed an apatite composite layer including the bone morphogenetic protein-2 (BMP-2) gene and fibronectin (FB), and we evaluated its ability to induce bone formation. Methods An apatite composite layer was evaluated to determine the efficiency of gene transfer to cells cultured on it. Cells were cultured on a composite layer including the BMP-2 gene and FB, and BMP-2 gene expression, BMP-2 protein concentrations, alkaline phosphatase (ALP) activity, and osteocalcin (OC) concentrations were measured. A bone defect on the cranium of rats was treated with hydroxyapatite (HAP)-coated ceramic buttons with the apatite composite layer including the BMP-2 gene and FB (HAP-BMP-FB). The tissue concentration of BMP-2, bone formation, and the expression levels of the BMP-2, ALP, and OC genes were all quantified. Results The apatite composite layer provided more efficient gene transfer for the cultured cells than an apatite composite layer without FB. The BMP-2 concentration was approximately 100~600 pg/mL in the cell-culture medium. Culturing the cells on the apatite composite layer for 27 days increased ALP activity and OC concentrations. In animal experiments, the tissue concentrations of BMP-2 were over 100 pg/mg in the HAP-BMP-FB group and approximately 50 pg/mg in the control groups. Eight weeks later, bone formation was more enhanced in the HAP-BMP-FB group than in the control groups. In the tissues surrounding the HAP button, the gene expression levels of ALP and OC increased. Conclusion The BMP-2 gene-FB-apatite composite layer might be useful for bone engineering.

2011-01-01

299

Biological properties of bone marrow-derived early and late endothelial progenitor cells in different culture media.  

PubMed

Ex vivo expansion of endothelial progenitor cells (EPCs) may be a promising strategy to overcome the clinical problem of limited cell numbers. As the culture medium is the key for the cell characteristics, the effects of different culture media on EPCs were investigated in the present study. Rat bone marrow mononuclear cells were cultured in different media, including M-199 media with 20% fetal bovine serum (FBS) and bovine pituitary extract (M1); M-199 media with 10% FBS, 20 ng/ml vascular endothelial growth factor (VEGF) and 10 ng/ml basic fibroblast growth factor (bFGF; M2) or epidermal growth medium (EGM)-2MV media. The cell morphology and biological functions, such as proliferation, adhesion, migration, tube formation and nitric oxide (NO) production were subsequently assayed in vitro. Moreover, endothelial biomarkers and apoptosis were also analyzed. The results showed that endothelial?like cells appeared in all of the culture systems. First?passage cells, namely early EPCs, tended to form colonies in M2 and EGM-2MV media but showed a fusiform shape in M1 media. The 3rd or 4th generation EPCs, namely late EPCs, cultured in EGM-2MV media exhibited increased adhesion, migration, tube formation and NO production as compared with EPCs in M1 or M2 media. Furthermore, late EPCs cultured in EGM-2MV expressed higher levels of endothelial cell markers, such as von Willibrand factor (vWF)and CD31, but relatively greater levels of apoptosis were observed. In conclusion, cell culture conditions, for example the medium used, affects the biological properties of bone marrow-derived early and late EPCs. PMID:24126824

Guan, Xiu M; Cheng, Min; Li, Hong; Cui, Xiao D; Li, Xin; Wang, Yu L; Sun, Jin L; Zhang, Xiao Y

2013-10-09

300

Heterotopic bone formation around vessels: pilot study of a new animal model.  

PubMed

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; Zwahlen, Roger A

2013-08-01

301

Effects of geometry of hydroxyapatite as a cell substratum in BMP-induced ectopic bone formation.  

PubMed

Three different types of porous hydroxyapatite with pore sizes of 100-200 micrometer in diameter-porous particles of hydroxyapatite (PPHAP), porous blocks of hydroxyapatite (PBHAP), and honeycomb-shaped hydroxyapatite (HCHAP)-were compared in terms of their abilities to induce osteogenesis when implanted subcutaneously with recombinant human BMP-2 into rats and extracted at 1, 2, 3, and 4 weeks. Histologically, direct bone formation occurred in PPHAP and PBHAP while only endochondral ossification took place in HCHAP. Interestingly, cartilage in the central zones and bone in the orifice zones of the tunnels of the HCHAP were observed at 2 weeks. After 3 weeks, the cartilage disappeared and bone formation occurred throughout the inner surface of the tunnels of the HCHAP, always leaving space for capillaries within the tunnels. Alkaline phosphatase activity and osteocalcin content were the highest in HCHAP among the three hydroxyapatite implants. These results clearly indicate that BMP-induced bone formation is highly dependent on the geometry of the carrier, which provides feasible structural factors for vascularization. PMID:10880093

Jin, Q M; Takita, H; Kohgo, T; Atsumi, K; Itoh, H; Kuboki, Y

2000-09-01

302

Digital measurements: a different approach to evaluate bone formation. A technical report.  

PubMed

In this study a digital measurement technique has been proposed to quantify bone formation on histological images. Two standard parietal defects were created in 30 adult rabbits. The animals were divided into six groups. Four animals of each group were randomly chosen as experimental group in which osteopontin-coated hydroxyapatite (OPN-HA) and hydroxyapatite (HA) were inserted alternatively in created defects. To observe the spontaneous healing process of defects, one animal of each group was used as control animal and these created defects did not receive any implants. The animals were sacrificed after 1, 2, 6, 12, 18 and 30 weeks. The histological sections were magnified (x100) and scanned digitally. The newly formed bone surfaces within the healing area were indicated and quantified by means of Adobe Photoshop 7 software. This measuring technique was found to be reliable and reproducible. The results of this study show no significant differences in bone formation between the OPN-HA and non-coated HA defects, although a significant difference in bone formation was measured at the margins of the defects treated with OPN-HA. PMID:17409740

Gordjestani, M; Dermaut, L; De Ridder, L; De Waele, P; De Leersnijder, W; Bosman, F

2006-01-01

303

QUALITY CONTROLLED RADIOCARBON DATING OF BONES AND CHARCOAL FROM THE EARLY PRE-POTTERY NEOLITHIC B (PPNB) OF MOTZA (ISRAEL)  

Microsoft Academic Search

Radiocarbon dating of early Pre-Pottery Neolithic B (PPNB) deposits at the site of Motza, Israel, was achieved by first prescreening many charcoal and bone samples in order to identify those that are in the most suitable state of preser- vation for dating. For assessing bone preservation, we determined the collagen contents, and by infrared spectroscopy the collagen purity. The collagen

Meirav Yizhaq; Genia Mintz; Illit Cohen; Hamudi Khalaily; Steve Weiner; Elisabetta Boaretto

304

449. Sca1+ Cell-Based Gene Therapy with a Modified Fibroblast Growth Factor 2 (FGF2) Increased Endosteal\\/Trabecular Bone Formation in Mice  

Microsoft Academic Search

A major problem in bone-wasting diseases such as osteoporosis is the loss of endosteal bone that results in reduced bone strength and increased fracture risk. Recent advances in gene therapy raise the possibility that ex vivo gene therapy with a bone-forming gene may be used to enhance endosteal bone formation. However, a successful strategy requires that the transduced cells remain

Susan L. Hall; K.-H. William Lau; Shin-Tai Chen; Matilda H.-C. Sheng; Apurva K. Srivastava; Henry J. Klamut; Jon E. Wergedal; Daila S. Gridley; Subburaman Mohan; David J. Baylink

2006-01-01

305

Effects of magnetic resonance imaging (MRI) on the formation of mouse dentin and bone  

SciTech Connect

The effects of magnetic resonance imaging (MRI) on dentin and bone formation in mice were examined using standard autoradiographic and liquid scintillation procedures. It was observed that exposure to a standard 23.2 min clinical multislice MRI (0.15T) procedure caused a significant increase in the synthesis of the collagenous matrix of dentin in the incisors of mice. There were no significant effects on alveolar and tibial bone matrix synthesis. These results suggest that the magnetic fields associated with MRI can affect the activity of cells and/or tissues that are involved in rapid synthetic activity.

Kwong-Hing, A.; Sandhu, H.S.; Prato, F.S.; Frappier, J.R.; Kavaliers, M. (Univ. of Western Ontario, London (Canada))

1989-10-01

306

Early Physical Activity Provides Sustained Bone Health Benefits Later in Childhood  

PubMed Central

Purpose This study examined the potential effect of early childhood moderate and vigorous physical activity (MVPA) on later bone health. Methods Three hundred and thirty-three children, participating in the Iowa Bone Development Study, were studied at ages 5, 8, and 11. MVPA (min/d) was measured using an accelerometry-based physical activity monitor. Bone mineral content (BMC, g) of the whole body, lumbar spine, and hip was measured using dual energy x-ray absorptiometry (DXA). Mixed regression models were used to test whether age 5 MVPA had an effect on BMC at ages 8 and 11, after adjustment for concurrent height, weight, age, maturity, and MVPA. The analysis was repeated to control for age 5 bone outcomes. Mixed model least-squares means at the person level of covariates for age group were used to compare the BMC at age 8 and 11 of children in the highest and lowest quartiles of age 5 MVPA. Results For boys and girls, age 5 MVPA predicted BMC adjusted for concurrent height, weight, age, maturity, and MVPA at ages 8 and 11 (p<0.05). When the analysis was repeated to also control for age 5 BMC, the effect of age 5 MVPA was significant for boys but not girls. Boys and girls in the highest age 5 MVPA quartile had 4 to 14% more BMC at age 8 and 11 than those in the lowest age 5 MVPA quartile (p < 0.05). Conclusion These results provide support for the benefits of early MVPA on sustained bone health during childhood especially for boys. Results indicate the importance of increasing MVPA as a strategy to improve BMC later in childhood.

Janz, Kathleen F.; Letuchy, Elena M.; Eichenberger Gilmore, Julie M.; Burns, Trudy L.; Torner, James C.; Willing, Marcia C.; Levy, Steven M.

2010-01-01

307

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.

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

2012-01-01

308

Insulin-like growth factor I has independent effects on bone matrix formation and cell replication  

SciTech Connect

The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of (2,3-/sup 3/H)proline and (methyl-/sup 3/H)thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on (/sup 3/H)proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on (/sup 3/H)thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis.

Hock, J.M.; Centrella, M.; Canalis, E.

1988-01-01

309

Osteoblast and osteocyte-specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing.  

PubMed

Connexin43 (Cx43) plays an important role in osteoblastic differentiation in vitro, and bone formation in vivo. Mice with osteoblast/osteocyte-specific loss of Cx43 display decreased gap junctional intercellular communication (GJIC), bone density, and cortical thickness. To determine the role of Cx43 in fracture healing, a closed femur fracture was induced in Osteocalcin-Cre+; Cx43(flox/flox) (Cx43cKO) and Cre-; Cx43(flox/flox) (WT) mice. We tested the hypothesis that loss of Cx43 results in decreased bone formation and impaired healing following fracture. Here, we show that osteoblast and osteocyte-specific deletion of Cx43 results in decreased bone formation, bone remodeling, and mechanical properties during fracture healing. Cx43cKO mice display decreased bone volume, total volume, and fewer TRAP+ osteoclasts. Furthermore, loss of Cx43 in mature osteoblasts and osteocytes results in a significant decrease in torsional rigidity between 21 and 35 days post-fracture, compared to WT mice. These studies identify a novel role for the gap junction protein Cx43 during fracture healing, suggesting that loss of Cx43 can result in both decreased bone formation and bone resorption. Therefore, enhancing Cx43 expression or GJIC may provide a novel means to enhance bone formation during fracture healing. PMID:22718243

Loiselle, Alayna E; Paul, Emmanuel M; Lewis, Gregory S; Donahue, Henry J

2012-06-20

310

Effects of Exemestane, Anastrozole and Tamoxifen on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Early Breast Cancer Patients: Results of N-SAS BC 04, the TEAM Japan Substudy  

Microsoft Academic Search

Background: Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patients treated with exemestane, anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer. Patients and Methods: Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone substudy were randomly assigned

T. Aihara; K. Suemasu; H. Takei; Y. Hozumi; M. Takehara; T. Saito; S. Ohsumi; N. Masuda; Y. Ohashi

2010-01-01

311

Use of ultrasonography in evaluation of new bone formation in patients treated by the method of Ilizarov.  

PubMed

(Full text is available at http://www.manu.edu.mk/prilozi). Background: Lengthening of bones by gradually distracting bone fragments using an external apparatus by Ilizarov, is a long process with numerous complications. The greatest threats in limb lengthening are poor new bone formation as well as premature consolidation of the newly generated bone. The purpose of this study was to determine the importance of ultrasonography in evaluation of bone formation in limb lengthening. Patients and Methods: The study involved 31 patients, in whom 52 long bones were lengthened by the Ilizarov method at the University Clinic for Orthopaedic Surgery in Skopje from 2006 to 2010. The study revealed the results of ultrasonographic analysis of new bone formation at four various stages of limb lengthening. The analysis of the results of ultrasonographic examination of bones throughout the lengthening process was based on the form and dimensions of the obtained ultrasonographic parameters - indicators of new bone formation - as well as on the appearance of the cortical margin at the distraction site. Results: Tiny, solitary and confluent hypo-echogenic foci developed on sonograms approximately 2 weeks after distraction was commenced. At stage I a new cortical margin was detected in 30.77%. The number of initial small indicators significantly decreased throughout lengthening. At stage IV the solitary indicators rate was 9.51%, whereas the linear indicators rate significantly increased from 22.12% at the first stage to 54.3% at the last stage. the cortical margin was presented in all 52 bones at III and IV stage of lengthening. Discussion and Conclusions: Ultrasonography enabled an evaluation of the degree of new bone formation and it preceded the radiographic changes at the distraction site. This helped to determine the surgical lengthening and to avoid numerous complications. Key words: Limb lengthening, new bone formation, ultrasonography. PMID:22952105

Poposka, A; Atanasov, N; Dzoleva-Tolevska, R

2012-07-01

312

Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club  

Microsoft Academic Search

Cancer treatment-induced bone loss (CTIBL) is one of the most important side effects of adjuvant antineoplastic treatment\\u000a in hormone-dependent neoplasms. Chemotherapy, GnRH analogs and tamoxifen can induce marked bone loss in premenopausal women\\u000a with early breast cancer. Aromatase inhibitors (AIs) are replacing tamoxifen as the preferred treatment for postmenopausal\\u000a women. As a class effect, steroidal (exemestane) and non-steroidal (anastrozole and

J. J. Body; P. Bergmann; S. Boonen; Y. Boutsen; J. P. Devogelaer; S. Goemaere; J. Y. Reginster; S. Rozenberg; J. M. Kaufman

2007-01-01

313

Application of osteomucoperiosteal flap in large unicystic ameloblastoma to promote early bone healing: An alternative to primary bone grafting  

PubMed Central

Background: The unicystic variety of ameloblastoma is reported to be significantly less prone to recurrence in young patients than its conventional counterpart, and therefore can be treated conservatively. This paper describes a technique of using an osteoperiosteal flap to allow complete enucleation of a unicystic ameloblastoma. The technique maintains the continuity of the mandible and restores full thickness as well as strength of the mandible to promote early healing. It also maintains blood supply and proper facial contour so that esthetics is unimpaired. Materials and Methods: We describe two cases of unicystic ameloblastoma in which we used an osteoperiosteal flap. This flap was then infractured at the lower border to obliterate the dead space. Results: The sequential radiographs demonstrate early incorporation of the graft and complete filling of the defect by 3 months. At 5 years of follow-up in our first case, complete healing of bone was observed. Conclusions: We believe that these procedures can be the treatment of choice in such cases, especially with larger lesions, as these rapidly restore the patient's facial contour to normal as well as reduce the healing time.

Khare, Gagan; Kumar, Sanjeev

2011-01-01

314

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

SciTech Connect

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

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

1982-05-01

315

Controls on the formation of early diagenetic dolomite, Monterey Formation, California  

SciTech Connect

The clayey siliceous and phosphatic Monterey Formation in the Santa Maria basin contains 1 to 40 wt % dolomite, whose stratigraphic occurrence is relatable to sediment composition which in turn is dependent on climatic variations. Early dolomite is commonly associated with laminated, organic-rich, calcareous, phosphatic sediment in which organic carbon, pyritic sulfur, V, and Cu are positively correlated. The amounts of organic matter and calcite affect the extent of early dolomite precipitation. Bacterial degradation of sediment organic matter reduces sulfate to H/sub 2/S and increases the carbonate alkalinity, highly supersaturating pore waters with respect to dolomite. Mg transport by diffusion from overlying sea water constrains the bulk of the dolomite to have formed during early diagenesis, in agreement with field evidence of precompaction origin. Ultimately Monterey sediment composition was influenced by the effects of climatic oscillations on surface water productivity. Global temperature decrease accelerates atmospheric and oceanic circulation and O/sub 2/ renewal rates to deep waters and deepens the carbonate compensation depth (CCD), thereby limiting organic matter and calcite preservation. Organic-rich sediment forms both in upwelling regions because of high surface productivity and infringement of an expanded O/sub 2/-minimum zone, and in basins where circulation is restricted by topography. Calcite content depends on the silica/calcite ratio of the surface productivity and on the CCD and basin bathymetry.

Compton, J.S.; Siever, R.

1985-01-01

316

Star-formation and LLAGN in Early-Type Galaxies  

NASA Astrophysics Data System (ADS)

We present the preliminary results for a project which will ultimately provide the first accurate, statistical picture of the relative importance of Low-Luminosity Active Galactic Nuclei (LLAGN) and star formation (SF) in the ATLAS-3D sample (Cappellari et al. 2011) of 260 early-type galaxies (ETGs). The sample has a host of photometric and integral-field spectroscopic measurements already available in the optical and millimeter regimes, making it an ideal sample to draw from for galaxy evolution studies. We will use this multiwavelength, ancillary data in concert with our deep ( 25 micro-Jy per beam rms), multifrequency radio continuum observations from the newly-upgraded EVLA to distinguish between the dominant nuclear emission mechanism, SF or LLAGN, in ETGs. At this time, we present the goals and methodology of our project as well as the results of a pilot EVLA study of a sub-sample of 20 ATLAS-3D galaxies observed at 1.4 and 5 GHz chosen to have a variety of CO, IR and radio properties. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.

Nyland, Kristina; Young, L.; Wrobel, J.; Morganti, R.; Sarzi, M.; Cappellari, M.; McDermid, R.; Krajnovic, D.; Emsellem, E.

2012-01-01

317

Metastasin S100A4 is a mediator of sex hormone-dependent formation of the cortical bone.  

PubMed

S100A4 is a Ca-binding protein participating in regulation of cell growth, survival, and motility. Here we studied the role of S100A4 protein in sex hormone-regulated bone formation. Bone mineral density in the trabecular and cortical compartments was evaluated in female S100A4 knockout (KO), in matched wild-type (WT) counterparts, and in WT mice treated with lentiviral small hairpin RNA construct inhibiting the S100A4 gene transcription or with a nontargeting construct, by peripheral quantitative computed tomography. The effect of sex hormones on bone was measured 5 weeks after ovariectomy (OVX) and/or dehydroepiadrosterone treatment. S100A4KO had an excessive trabecular and cortical bone formation compared with the age- and sex-matched WT mice. S100A4KO had an increased periosteal circumference (P = .001), cortical thickness (P = .056), and cortical area (P = .003), which predicted 20% higher bone strength in S100A4KO (P = .013). WT mice treated with small hairpin RNA-S100A4 showed an increase of the cortical bone parameters in a fashion identical with S100A4KO mice, indicating the key role of S100A4 in the changed bone formation. S100A4KO mice had higher serum levels of osteocalcin and a higher number of osteocalcin-positive osteoblasts under the periosteum. OVX-S100A4 resulted in the loss of the cortical bone supported by high CTX-I levels, whereas no such changes were observed in OVX-WT mice. S100A4KO mice resisted the dehydroepiadrosterone -induced bone formation observed in the WT counterparts. Our study indicates that S100A4 is a regulator of bone formation, which inhibits bone excess in the estrogen-sufficient mice and prevents the cortical bone loss in the estrogen-deprived mice. PMID:23798573

Erlandsson, Malin C; Bian, Li; Jonsson, Ing-Marie; Andersson, Karin M; Bokarewa, Maria I

2013-06-24

318

Silicon deprivation decreases collagen formation in wounds and bone, and ornithine transaminase enzyme activity in liver.  

PubMed

We have shown that silicon (Si) deprivation decreases the collagen concentration in bone of 9-wk-old rats. Finding that Si deprivation also affects collagen at different stages in bone development, collagen-forming enzymes, or collagen deposition in other tissues would have implications that Si is important for both wound healing and bone formation. Therefore, 42 rats in experiment 1 and 24 rats in experiment 2 were fed a basal diet containing 2 or 2.6 microg Si/g, respectively, based on ground corn and casein, and supplemented with either 0 or 10 microg Si/g as sodium metasilicate. At 3 wk, the femur was removed from 18 of the 42 rats in experiment 1 for hydroxyproline analysis. A polyvinyl sponge was implanted beneath the skin of the upper back of each of the 24 remaining rats. Sixteen hours before termination and 2 wk after the sponge had been implanted, each rat was given an oral dose of 14C-proline (1.8 microCi/100 g body wt). The total amount of hydroxyproline was significantly lower in the tibia and sponges taken from Si-deficient animals than Si-supplemented rats. The disintegrations per minute of 14C-proline were significantly higher in sponge extracts from Si- deficient rats than Si-supplemented rats. Additional evidence of aberrations in proline metabolism with Si deprivation was that liver ornithine aminotransferase was significantly decreased in Si-deprived animals in experiment 2. Findings of an increased accumulation of 14C-proline and decreased total hydroxyproline in implanted sponges and decreased activity of a key enzyme in proline synthesis (liver ornithine aminotransferase) in Si-deprived animals indicates an aberration in the formation of collagen from proline in sites other than bone that is corrected by Si. This suggests that Si is a nutrient of concern in wound healing as well as bone formation. PMID:12462748

Seaborn, C D; Nielsen, F H

2002-12-01

319

Low-level accelerations applied in the absence of weight bearing can enhance trabecular bone formation.  

PubMed

High-frequency whole body vibrations can be osteogenic, but their efficacy appears limited to skeletal segments that are weight bearing and thus subject to the induced load. To determine the anabolic component of this signal, we investigated whether low-level oscillatory displacements, in the absence of weight bearing, are anabolic to skeletal tissue. A loading apparatus, developed to shake specific segments of the murine skeleton without the direct application of deformations to the tissue, was used to subject the left tibia of eight anesthesized adult female C57BL/6J mice to small (0.3 g or 0.6 g) 45 Hz sinusoidal accelerations for 10 min/day, while the right tibia served as an internal control. Video and strain analysis revealed that motions of the apparatus and tibia were well coupled, inducing dynamic cortical deformations of less than three microstrain. After 3 weeks, trabecular metaphyseal bone formation rates and the percentage of mineralizing surfaces (MS/BS) were 88% and 64% greater (p < 0.05) in tibiae accelerated at 0.3 g than in their contralateral controls. At 0.6 g, bone formation rates and mineral apposition rates were 66% and 22% greater (p < 0.05) in accelerated tibiae. Changes in bone morphology were evident only in the epiphysis, where stimulated tibiae displayed significantly greater cortical area (+8%) and thickness (+8%). These results suggest that tiny acceleratory motions--independent of direct loading of the matrix--can influence bone formation and bone morphology. If confirmed by clinical studies, the unique nature of the signal may ultimately facilitate the stimulation of skeletal regions that are prone to osteoporosis even in patients that are suffering from confinement to wheelchairs, bed rest, or space travel. PMID:17318899

Garman, Russell; Gaudette, Glenn; Donahue, Leah-Rae; Rubin, Clinton; Judex, Stefan

2007-06-01

320

Cancellous bone formation response to simulated resistance training during disuse is blunted by concurrent alendronate treatment.  

PubMed

The purpose of this study was to assess the effectiveness of simulated resistance training (SRT) exercise combined with alendronate (ALEN) in mitigating or preventing disuse-associated losses in cancellous bone microarchitecture and formation. Sixty male Sprague-Dawley rats (6 months old) were randomly assigned to either cage control (CC), hind limb unloading (HU), HU plus either ALEN (HU?+?ALEN), SRT (HU?+?SRT), or a combination of ALEN and SRT (HU?+?SRT/ALEN) for 28 days. HU?+?SRT and HU?+?SRT/ALEN rats were anesthetized and subjected to muscle contractions once every 3 days during HU (four sets of five repetitions, 1000?ms isometric?+?1000?ms eccentric). Additionally, HU?+?ALEN and HU?+?SRT/ALEN rats received 10?µg/kg of body weight of ALEN three times per week. HU reduced cancellous bone-formation rate (BFR) by 80%, with no effect of ALEN treatment (-85% versus CC). SRT during HU significantly increased cancellous BFR by 123% versus CC, whereas HU?+?SRT/ALEN inhibited the anabolic effect of SRT (-70% versus HU?+?SRT). SRT increased bone volume and trabecular thickness by 19% and 9%, respectively, compared with CC. Additionally, osteoid surface (OS/BS) was significantly greater in HU?+?SRT rats versus CC (+32%). Adding ALEN to SRT during HU reduced Oc.S/BS (-75%), Ob.S/BS (-72%), OS/BS (-61%), and serum TRACP5b (-36%) versus CC. SRT and ALEN each independently suppressed a nearly twofold increase in adipocyte number evidenced with HU and inhibited increases in osteocyte apoptosis. These results demonstrate the anabolic effect of a low volume of high-intensity muscle contractions during disuse and suggest that both bone resorption and bone formation are suppressed when SRT is combined with bisphosphonate treatment. PMID:21509821

Swift, Joshua M; Swift, Sibyl N; Nilsson, Mats I; Hogan, Harry A; Bouse, Scott D; Bloomfield, Susan A

2011-09-01

321

[Development of artificial implant bone].  

PubMed

This study tested the hypothesis that a significant amount of the new bone produced by heterotopic periosteal grafts is derived osteoinductively because proliferating periosteal cells express the bone morphogenetic protein (BMP). Rabbit ulnar and radial periosteum were autografted as free grafts (FGs) to the forelimb musculature, and as millipore diffusion chambers grafts (MDCGs) to the rectus abdominus muscle. The sections were immunostained with monoclonal antibody against recombinant human (rh) BMP-2. Sections from FGs recovered 5 to 28 days postoperatively exhibited cartilage and bone; fibrous tissue, cartilage, bone, and osteochondroid differentiated within MDCGs. Although BMP-2 was expressed by mesenchymal cells, osteoblasts, osteocytes, and osteoclasts, none of the MDCGs produced the osteoinductive signature of transmembrane bone formation. These observations indicated that the larger fraction of the new bone produced by heterotopic periosteal autografts is derived from the graft cells. As the artificial implant bone, 1) the freeze-dried bone, 2) autoclaved bone, 3) sintered bone, 4) hydroxyapatite, and 5) titanium metal were used. Sprague-Dawley rats (aged 8 weeks) were used, the parietal bone was cut off, they were treated to freeze-dried bone, autoclaved bone and sintered bone. Then each treated bone was reimplanted. The grafts were harvested at 1, 2, 3, and 5 weeks postoperatively, the specimens were observed with a scanning electron microscope and a conventional light microscope. All of the treated bone were able to bone union, especially in the sintered bone and autoclaved bone, the blood vessels and the bone formation were produced at extremely early stage. In implantation of the non-living body materials, bone formation and revascularization was inhibited. We think that bone transplantation after irradiation should be done after recovery from the radiation damage to the periosteal cells and the blood vessels. PMID:10736757

Kita, S

2000-01-01

322

CXCR4 antagonism attenuates load-induced periosteal bone formation in mice.  

PubMed

Mechanical loading is a key anabolic regulator of bone mass. Stromal cell-derived factor-1 (SDF-1) is a stem cell homing factor that is important in hematopoiesis, angiogenesis, and fracture healing, though its involvement in skeletal mechanoadaptation is virtually unknown. The objective of this study was to characterize skeletal expression patterns of SDF-1 and CXCR4, the receptor for SDF-1, and to determine the role of SDF-1 signaling in load-induced periosteal bone formation. Sixteen-week-old C57BL/6 mice were treated with PBS or AMD3100, an antagonist against CXCR4, and exposed to in vivo ulnar loading (2.8 N peak-to-peak, 2?Hz, 120 cycles). SDF-1 was expressed in cortical and trabecular osteocytes and marrow cells, and CXCR4 was primarily expressed in marrow cells. SDF-1 and CXCR4 expression was enhanced in response to mechanical stimulation. The CXCR4 receptor antagonist AMD3100 significantly attenuated load-induced bone formation and led to smaller adaptive changes in cortical geometric properties as determined by histomorphometric analysis. Our data suggest that SDF-1/CXCR4 signaling plays a critical role in skeletal mechanoadaptation, and may represent a unique therapeutic target for prevention and treatment of age-related and disuse bone loss. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1828-1838, 2013. PMID:23881789

Leucht, Philipp; Temiyasathit, Sara; Russell, Ashley; Arguello, Juan F; Jacobs, Christopher R; Helms, Jill A; Castillo, Alesha B

2013-07-23

323

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

NASA Astrophysics Data System (ADS)

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

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

2004-06-01

324

Synthesis of novel 2-benzothiopyran and 3-benzothiepin derivatives and their stimulatory effect on bone formation.  

PubMed

In a search for therapeutic agents for the treatment of osteoporosis and bone fracture, we found that 2-benzothiopyran-1-carboxamide derivatives 1, derived from ipriflavone as a lead compound, increase cellular alkaline phosphatase activity in cultures of rat bone marrow stromal cells. Further modification of 1 has led to the discovery of more potent 3-benzothiepin-2-carboxamide derivatives 2. Of these, 3-benzothiepin derivatives bearing a 4-(dialkoxyphosphorylmethyl)phenyl group on the 2-carboxamide moiety such as 2h and 2q exhibited significant improvement of activity compared to ipriflavone. Asymmetric synthesis of 2h and 2q revealed that the (-)-isomers possessed activities superior to those of the (+)-isomers. Further evaluation of these compounds using the mouse osteoblastic cell line MC3T3-E1 revealed that (-)-2q enhanced the effect of bone morphogenetic protein. In addition, application of a sustained-release agent containing 2q increased the area of newly formed bone in a rat skull defect model. Based on these findings, (-)-2q was selected for further investigation as a new drug stimulating bone formation. Synthesis and structure-activity relationships for this novel series of 2-benzothiopyran and 3-benzothiepin derivatives are detailed. PMID:10052981

Oda, T; Notoya, K; Gotoh, M; Taketomi, S; Fujisawa, Y; Makino, H; Sohda, T

1999-02-25

325

Parathyroid hormone induces bone formation in phosphorylation-deficient PTHR1 knockin mice  

PubMed Central

Activation of G protein-coupled receptors by agonists leads to receptor phosphorylation, internalization of ligand receptor complexes, and desensitization of hormonal response. The role of parathyroid hormone (PTH) receptor 1, PTHR1, is well characterized and known to regulate cellular responsiveness in vitro. However, the role of PTHR1 phosphorylation in bone formation is yet to be investigated. We have previously demonstrated that impaired internalization and sustained cAMP stimulation of phosphorylation-deficient (PD) PTHR1 leads to exaggerated cAMP response to subcutaneous PTH infusion in a PD knockin mouse model. To understand the physiological role of receptor internalization on PTH bone anabolic action, we examined bone parameters of wild-type (WT) and PD knockin female and male mice following PTH treatment. We found a decrease in total and diaphyseal bone mineral density in female but not in male PD mice compared with WT controls at 3–6 mo of age. This effect was attenuated at older age groups. PTH administration displayed increased bone volume and trabecular thickness in the vertebrae and distal femora of both WT and PD animals. These results suggest that PTHR1 phosphorylation does not play a major role in the anabolic action of PTH.

Samra, Tareq A.; Abou-Samra, Abdul B.

2012-01-01

326

The role of synthetic and bone extracted Ca-phospholipid-PO 4 complexes in hydroxyapatite formation  

Microsoft Academic Search

Summary The calcium-phospholipid-phosphate (Ca-PL-PO4) complex isolated from young bone has been shown to initiate hydroxyapatite formation from a metastable calcium phosphate solution. The action of the complex was compared to that of the acidic phospholipids: phosphatidyl serine, phosphatidyl inositol and phosphatidic acid. These phospholipids first remove calcium, and a small amount of phosphate from the metastable solution forming a material

Adele L. Boskey; Aaron S. Posner

1977-01-01

327

Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations  

Microsoft Academic Search

Introduction  Statins are drugs that inhibit HMG Co-A reductase and have been shown to enhance bone formation in vitro and in vivo in rodents.\\u000a However, the statins currently used for cholesterol-lowering have been selected for their capacity to target the liver where\\u000a their effects on cholesterol synthesis are mediated and they undergo first pass metabolism. When given in lipid-lowering doses,\\u000a these

G. E. Gutierrez; D. Lalka; I. R. Garrett; G. Rossini; G. R. Mundy

2006-01-01

328

Bone mineral density in partially recovered early onset anorexic patients - a follow-up investigation  

PubMed Central

Background and aims There still is a lack of prospective studies on bone mineral development in patients with a history of early onset Anorexia nervosa (AN). Therefore we assessed associations between bone mass accrual and clinical outcomes in a former clinical sample. In addition to an expected influence of regular physical activity and hormone replacement therapy, we explored correlations with nutritionally dependent hormones. Methods 3-9 years (mean 5.2 ± 1.7) after hospital discharge, we re-investigated 52 female subjects with a history of early onset AN. By means of a standardized approach, we evaluated the general outcome of AN. Moreover, bone mineral content (BMC) and bone mineral density (BMD) as well as lean and fat mass were measured by dual-energy x-ray absorptiometry (DXA). In a substudy, we measured the serum concentrations of leptin and insulin-like growth factor-I (IGF-I). Results The general outcome of anorexia nervosa was good in 50% of the subjects (BMI ? 17.5 kg/m2, resumption of menses). Clinical improvement was correlated with BMC and BMD accrual (?2 = 5.62/?2 = 6.65, p = 0.06 / p = 0.036). The duration of amenorrhea had a negative correlation with BMD (r = -.362; p < 0.01), but not with BMC. Regular physical activity tended to show a positive effect on bone recovery, but the effect of hormone replacement therapy was not significant. Using age-related standards, the post-discharge sample for the substudy presented IGF-I levels below the 5th percentile. IGF-I serum concentrations corresponded to the general outcome of AN. By contrast, leptin serum concentrations showed great variability. They correlated with BMC and current body composition parameters. Conclusions Our results from the main study indicate a certain adaptability of bone mineral accrual which is dependent on a speedy and ongoing recovery. While leptin levels in the substudy tended to respond immediately to current nutritional status, IGF-I serum concentrations corresponded to the individual's age and general outcome of AN.

2010-01-01

329

Formation and processing of organics in the early solar system.  

PubMed

Until pristine samples can be returned from cometary nuclei, primitive meteorites represent our best source of information about organic chemistry in the early solar system. However, this material has been affected by secondary processing on asteroidal parent bodies which probably did not affect the material now present in cometary nuclei. Production of meteoritic organic matter apparently involved the following sequence of events: Molecule formation by a variety of reaction pathways in dense interstellar clouds; Condensation of those molecules onto refractory interstellar grains; Irradiation of organic-rich interstellar-grain mantles producing a range of molecular fragments and free radicals; Inclusion of those interstellar grains into the protosolar nebula with probable heating of at least some grain mantles during passage through the shock wave bounding the solar accretion disc; Agglomeration of residual interstellar grains and locally produced nebular condensates into asteroid-sized planetesimals; Heating of planetesimals by decay of extinct radionuclides; Melting of ice to produce liquid water within asteroidal bodies; Reaction of interstellar molecules, fragments and radicals with each other and with the aqueous environment, possibly catalysed by mineral grains; Loss of water and other volatiles to space yielding a partially hydrated lithology containing a complex suite of organic molecules; Heating of some of this organic matter to generate a kerogen-like complex; Mixing of heated and unheated material to yield the meteoritic material now observed. Properties of meteoritic organic matter believed to be consistent with this scenario include: Systematic decrease of abundance with increasing C number in homologous series of characterisable molecules; Complete structural diversity within homologous series; Predominance of branched-chain isomers; Considerable isotopic variability among characterisable molecules and within kerogen-like material; Substantial deuterium enrichment in all organic fractions; Some fractions significantly enriched in nitrogen-15; Modest excesses of L-enantiomers in some racemisation-resistant molecules but no general enantiomeric preference. Despite much speculation about the possible role of Fischer-Tropsch catalytic hydrogenation of CO in production of organic molecules in the solar nebula, no convincing evidence for such material has been found in meteorites. A similarity between some meteoritic organics and those produced by Miller-Urey discharge synthesis may reflect involvement of common intermediates rather than the operation of electric discharges in the early solar system. Meteoritic organic matter constitutes a useful, but not exact, guide to what we shall find with in situ analytical and sample-return missions to cometary nuclei. PMID:11543289

Kerridge, J F

1999-01-01

330

Formation and Processing of Organics in the Early Solar System  

NASA Astrophysics Data System (ADS)

Until pristine samples can be returned from cometary nuclei, primitive meteorites represent our best source of information about organic chemistry in the early solar system. However, this material has been affected by secondary processing on asteroidal parent bodies which probably did not affect the material now present in cometary nuclei. Production of meteoritic organic matter apparently involved the following sequence of events: Molecule formation by a variety of reaction pathways in dense interstellar clouds; Condensation of those molecules onto refractory interstellar grains; Irradiation of organic-rich interstellar-grain mantles producing a range of molecular fragments and free radicals; Inclusion of those interstellar grains into the protosolar nebula with probable heating of at least some grain mantles during passage through the shock wave bounding the solar accretion disc; Agglomeration of residual interstellar grains and locally produced nebular condensates into asteroid-sized planetesimals; Heating of planetesimals by decay of extinct radionuclides; Melting of ice to produce liquid water within asteroidal bodies; Reaction of interstellar molecules, fragments and radicals with each other and with the aqueous environment, possibly catalysed by mineral grains; Loss of water and other volatiles to space yielding a partially hydrated lithology containing a complex suite of organic molecules; Heating of some of this organic matter to generate a kerogen-like complex; Mixing of heated and unheated material to yield the meteoritic material now observed. Properties of meteoritic organic matter believed to be consistent with this scenario include: Systematic decrease of abundance with increasing C number in homologous series of characterisable molecules; Complete structural diversity within homologous series; Predominance of branched-chain isomers; Considerable isotopic variability among characterisable molecules and within kerogen-like material; Substantial deuterium enrichment in all organic fractions; Some fractions significantly enriched in nitrogen-15; Modest excesses of L-enantiomers in some racemisation-resistant molecules but no general enantiomeric preference. Despite much speculation about the possible role of Fischer-Tropsch catalytic hydrogenation of CO in production of organic molecules in the solar nebula, no convincing evidence for such material has been found in meteorites. A similarity between some meteoritic organics and those produced by Miller-Urey discharge synthesis may reflect involvement of common intermediates rather than the operation of electric discharges in the early solar system. Meteoritic organic matter constitutes a useful, but not exact, guide to what we shall find with in situ analytical and sample-return missions to cometary nuclei.

Kerridge, John F.

1999-10-01

331

Hydroxyapatite bioactivated bacterial cellulose promotes osteoblast growth and the formation of bone nodules  

PubMed Central

The goal of this study was to investigate the feasibility of bacterial cellulose (BC) scaffold to support osteoblast growth and bone formation. BC was produced by culturing Acetobacter xylinum supplemented with hydroxyapatite (HA) to form BC membranes (without HA) and BC/HA membranes. Membranes were subjected to X-ray photoelectron spectroscopy (XPS) analysis to determine surface element composition. The membranes were further used to evaluate osteoblast growth, alkaline phosphatase activity and bone nodule formation. BC was free of calcium and phosphate. However, XPS analysis revealed the presence of both calcium (10%) and phosphate (10%) at the surface of the BC/HA membrane. Osteoblast culture showed that BC alone was non-toxic and could sustain osteoblast adhesion. Furthermore, osteoblast adhesion and growth were significantly (p ?0.05) increased on BC/HA membranes as compared to BC alone. Both BC and BC/HA membranes improved osteoconductivity, as confirmed by the level of alkaline phosphatase (ALP) activity that increased from 2.5 mM with BC alone to 5.3 mM with BC/HA. BC/HA membranes also showed greater nodule formation and mineralization than the BC membrane alone. This was confirmed by Alizarin red staining (ARS) and energy dispersive X-ray spectroscopy (EDX). This work demonstrates that both BC and BC/HA may be useful in bone tissue engineering.

2012-01-01

332

Self-consistent formation of continents on early Earth  

NASA Astrophysics Data System (ADS)

In our study we want to understand how Earth evolved with time and examine the initiation of plate tectonics and the possible formation of continents on Earth. Plate tectonics and continents seem to influence the likelihood of a planet to harbour life [1], and both are strongly influenced by the planetary interior (e.g. mantle temperature and rheology) and surface conditions (e.g. stabilizing effect of continents, atmospheric temperature), and may also depend on the biosphere. Earth is the only terrestrial planet (i.e. with a rocky mantle and iron core) in the solar system where long-term plate tectonics evolved. Knowing the factors that have a strong influence on the occurrence of plate tectonics allows for prognoses about plate tectonics on terrestrial exoplanets that have been detected in the past decade, and about the likelihood of these planets to harbour Earth-like life. For this purpose, planetary interior and surface processes are coupled via 'particles' as computational tracers in the 3D code GAIA [2,3]. These particles are dispersed in the mantle and crust of the modelled planet and can track the relevant rock properties (e.g. density or water content) over time. During the thermal evolution of the planet, the particles are advected due to mantle convection and along melt paths towards the surface and help to gain information about the thermo-chemical system. This way basaltic crust that is subducted into the silicate mantle is traced in our model. It is treated differently than mantle silicates when re-molten, such that granitic (felsic) crust is produced (similar to the evolution of continental crust on early Earth [4]), which is stored in the particle properties. We apply a pseudo-plastic rheology and use small friction coefficients (since an increased reference viscosity is used in our model). We obtain initiation of plate tectonics and self-consistent formation of pre-continents after a few Myr up to several Gyr - depending on the initial conditions and applied rheology. Furthermore, our first results indicate that continents can stabilize plate tectonics, analogous to the results obtained by [5]. The model will be further developed to treat hydration and dehydration of oceanic crust as well as subduction of carbonates to allow for a self-consistent 3D model of early Earth including a direct link between interior and atmosphere via both outgassing [6] and regassing. References [1] Ward, P.D. and Brownlee, D. (2000), Rare Earth, Springer. [2] Hüttig, C. and Stemmer, K. (2008), PEPI, 171(1-4):137-146. [3] Plesa, A.-C., Tosi, N. and Hüttig, C. (2013), in: Integrated Information and Computing Systems for Natural, Spatial, and Social Sciences, IGI Global, 302-323. [4] Arndt, N.T. and Nisbet, E.G. (2012), Annu. Rev. Earth Planet. Sci., 40:521-549. [5] Rolf, T. and Tackley, P.J. (2011), GRL, 38:L18301. [6] Noack, L., Breuer, D. and Spohn, T. (2012), Icarus, 217(2):484-498.

Noack, Lena; Van Hoolst, Tim; Breuer, Doris; Dehant, Véronique

2013-04-01

333

Effect of Early and Delayed Mechanical Loading on Tendon-to-Bone Healing After Anterior Cruciate Ligament Reconstruction  

PubMed Central

Background: Modulation of the mechanical environment may profoundly affect the healing tendon graft-bone interface. The purpose of this study was to determine how controlled axial loading after anterior cruciate ligament reconstruction affects tendon-to-bone healing. Our hypothesis was that controlled cyclic axial loading after a period of immobilization would improve tendon-to-bone healing compared with that associated with immediate axial loading or prolonged immobilization. Methods: One hundred and fifty-six male Sprague-Dawley rats underwent anterior cruciate ligament reconstruction with use of a flexor digitorum longus autograft. A custom-designed fixture was used to apply an external fixator across the knee parallel to the anterior cruciate ligament graft. Animals were randomly assigned to be treated with immobilization (n = 36) or controlled knee distraction along the long axis of the graft to achieve approximately 2% axial strain beginning (1) immediately postoperatively (n = 36), (2) on postoperative day 4 (“early delayed loading,” n = 42), or (3) on postoperative day 10 (“late delayed loading,” n = 42). The animals were killed at fourteen or twenty-eight days postoperatively for biomechanical testing, micro-computed tomography, and histomorphometric analysis of the bone-tendon-bone complex. Data were analyzed with use of a two-way analysis of variance followed by a post hoc Tukey test with p < 0.05 defined as significant. Results: Delayed initiation of cyclic axial loading on postoperative day 10 resulted in a load to failure of the femur-anterior cruciate ligament-tibia complex at two weeks that was significantly greater than that resulting from immediate loading or prolonged immobilization of the knee (mean and standard deviation, 9.6 ± 3.3 N versus 4.4 ± 2.3 N and 4.4 ± 1.5 N, respectively; p < 0.01). The new-bone formation observed in the tibial tunnels of the delayed-loading groups was significantly increased compared with that in the immediate-loading and immobilization groups at both two and four weeks postoperatively (1.47 ± 0.11 mm3 [postoperative-day-10 group] versus 0.89 ± 0.30 mm3 and 0.85 ± 0.19 mm3, respectively, at two weeks; p < 0.003). There were significantly fewer ED1+ inflammatory macrophages and significantly more ED2+ resident macrophages at the healing tendon-bone interface in both delayed-loading groups compared with the counts in the immediate-loading and immobilization groups at two and four weeks (2.97 ± 0.7 [postoperative day 10] versus 1.14 ± 0.47 and 1.71 ± 1.5 ED2+ cells, respectively, per high-power field at two weeks; p < 0.02). The numbers of osteoclasts in the delayed-loading groups were significantly lower than those in the immediate-loading and immobilization groups at two and four weeks postoperatively (0.35 ± 0.15 [postoperative-day-10 group] versus 1.02 ± 0.08 and 1.44 ± 0.2 cells, respectively, per high-power field at two weeks; p < 0.01), and the delayed-loading groups also had significantly reduced interface tissue vascularity compared with the other groups (p < 0.003). Conclusions: Delayed application of cyclic axial load after anterior cruciate ligament reconstruction resulted in improved mechanical and biological parameters of tendon-to-bone healing compared with those associated with immediate loading or prolonged postoperative immobilization of the knee. Clinical Relevance: This study of anterior cruciate ligament reconstruction may have important implications for rehabilitation after soft-tissue reconstructive procedures in the knee. Controlled mechanical loads after a delay to allow resolution of acute postoperative inflammation may be most favorable to the healing enthesis.

Bedi, Asheesh; Kovacevic, David; Fox, Alice J.S.; Imhauser, Carl W.; Stasiak, Mark; Packer, Jonathan; Brophy, Robert H.; Deng, Xiang-Hua; Rodeo, Scott A.

2010-01-01

334

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.

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

2013-01-01

335

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

336

A novel mouse model for the study of the inhibitory effects of chronic ethanol exposure on direct bone formation  

Technology Transfer Automated Retrieval System (TEKTRAN)

Excessive alcohol consumption has been reported to interfere with human bone homeostasis and repair in multiple ways. Previous studies have demonstrated that chronic ethanol exposure in the rat via an intragastric dietary delivery system inhibits direct bone formation during distraction osteogenesis...

337

Evaluation of a thiolated chitosan scaffold for local delivery of BMP-2 for osteogenic differentiation and ectopic bone formation.  

PubMed

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; Kook, Min-Suk; Kim, Sun-Hun; Koh, Jeong-Tae

2013-08-20

338

The Contribution of the Family to the Facilitation of Identity Formation in Early Adolescence  

Microsoft Academic Search

This paper explores the family's role in the facilitation of identity formation in early adolescence. First, studies that focus on the family's style of adapting to the transition from childhood into early adolescence are reviewed. Second, research on the relation between identity formation and family processes in late adolescence is reviewed in order to suggest directions for future research with

Harold D. Grotevant

1983-01-01

339

Effects of long-term diabetes and\\/or high-dose 17?-estradiol on bone formation, bone mineral density, and strenght in ovariectomized rats  

Microsoft Academic Search

Long-term diabetes in female rats preserves the bone mineral density (BMD) but impairs the strength of the femur. In this study, we have compared the effects of diabetes and high-dose 17?-estradiol (E2), two conditions of low bone formation, in ovariectomized (ovx) rats. Spontaneously diabetic BB rats were ovx 0–3 days after onset, and nondiabetic ovx littermates were used as controls;

J. Verhaeghe; G. Oloumi; E. van Herck; R. van Bree; J. Dequeker; T. A. Einhorn; R. Bouillon

1997-01-01

340

Exercise and Mechanical Loading Increase Periosteal Bone Formation and Whole Bone Strength in C57BL\\/6J Mice but Not in C3H\\/Hej Mice  

Microsoft Academic Search

.   To identify the genes, and the mechanisms that account for the 53% higher peak bone density in C3H\\/HeJ (C3H) mice compared\\u000a with C57BL\\/6J (B6) mice, we are performing quantitative trait locus and phenotypic analyses. The phenotypic studies revealed\\u000a differences in bone formation and resorption, and showed that hindlimb immobilization (by sciatic neurectomy) caused a greater\\u000a increase in endosteal resorption

Y. Kodama; Y. Umemura; S. Nagasawa; W. G. Beamer; L. R. Donahue; C. R. Rosen; D. J. Baylink; J. R. Farley

2000-01-01

341

Enhancement of recombinant human bone morphogenetic protein-2 (rhBMP-2)-induced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline  

Microsoft Academic Search

We investigated the enhancement of new bone |formation elicited ectopically by recombinant human bone morphogenetic protein-2 (rhBMP-2), using parathyroid hormone (PTH) and a phosphodiesterase inhibitor (PDEi), pentoxifylline (PTX), in an animal model. Collagen sponge sheet discs containing rhBMP were implanted onto the back muscles of mice. PTX alone (200?mg\\/kg body weight [BW]), PTH(1–34) (10?µg\\/kg BW), PTX plus PTH (200?mg\\/kg BW

Hiroshi Horiuchi; Naoto Saito; Tetsuya Kinoshita; Shinji Wakabayashi; Takahiro Tsutsumimoto; Satoru Otsuru; Kunio Takaoka

2004-01-01

342

Ectopic bone formation associated with recombinant human bone morphogenetic proteins-2 using absorbable collagen sponge and beta tricalcium phosphate as carriers  

Microsoft Academic Search

The ectopic bone formation of recombinant human bone morphogenetic protein-2(rhBMP-2) was evaluated using absorbable collagen sponges (ACS) and beta tricalcium phosphate (?-TCP) as carriers in a rat subcutaneous assay model. Subcutaneous pockets were created on the back of rats. The pockets were implanted with rhBMP-2\\/ACS, rhBMP-2\\/?-TCP, ACS alone, and ?-TCP alone. The rats were sacrificed at 2 or 8 weeks

Chang-Sung Kim; Joon-Il Kim; Jin Kim; Seong-Ho Choi; Jung-Kiu Chai; Chong-Kwan Kim; Kyoo-Sung Cho

2005-01-01

343

Effects of Vitamin K 2 and Risedronate on Bone Formation and Resorption, Osteocyte Lacunar System, and Porosity in the Cortical Bone of Glucocorticoid-Treated Rats  

Microsoft Academic Search

The purpose of the present study was to examine the effects of vitamin K2 and risedronate on bone formation and resorption, the osteocyte lacunar system, and porosity in the cortical bone of glucocorticoid\\u000a (GC)-treated rats. Forty-nine female Sprague-Dawley rats, 3 months of age, were randomized into five groups according to the\\u000a following treatment schedule: age-matched control, GC administration, and GC

Jun Iwamoto; Hideo Matsumoto; Tsuyoshi Takeda; Yoshihiro Sato; Xiaoqing Liu; James K. Yeh

2008-01-01

344

Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats  

PubMed Central

Background Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied. Methodology and Principal Findings In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation. Conclusions/Significance These results indicate: 1) a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

Zhang, Jian; Lazarenko, Oxana P.; Blackburn, Michael L.; Shankar, Kartik; Badger, Thomas M.; Ronis, Martin J. J.; Chen, Jin-Ran

2011-01-01

345

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

PubMed

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 (18)F-fluorodeoxy-glucose positron emission tomography CT ((18)F-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

346

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.

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

2010-01-01

347

Early and Mid Term Histological Events During Single Level Posterolateral Intertransverse Process Fusion With Rhbmp-2/Collagen Carrier and a Ceramic Bulking Agent In a Non-Human Primate Model: Implications for Bone Graft Preparation.  

PubMed

STUDY DESIGN:: We used a non-human primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. OBJECTIVE:: To examine early/mid-term descriptive histological and computerized tomographic events in single-level uninstrumented posterolateral non-human primate spinal fusions using rhBMP-2/ACS combined with ceramic bulking agents in three different configurations. SUMMARY OF BACKGROUND DATA:: rhBMP-2 on an absorbable collagen sponge carrier (ACS) alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in non-human primates. METHODS:: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite (HA)/tricalcium phosphate (?-TCP) ceramic bulking agent in three formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5?mg/cc (3.0?mg rhBMP-2) was combined with 2.5?cc of ceramic bulking agent per side. Animals were killed at 4 weeks and 12 weeks postoperative. Computerized tomography scans were performed immediately post-op and every 4 weeks until sacrifice. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. RESULTS:: Significant histological differences in the developing fusion appeared between the three rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. CONCLUSIONS:: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results as well as previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding as well as a structure to supporting bone formation of the developing fusion mass. PMID:23073151

Khan, Safdar N; Toth, Jeffrey M; Gupta, Kavita; Glassman, Steven D; Gupta, Munish C

2012-10-15

348

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

349

The early phases of bone healing can be differentiated in a rat osteotomy model by focused transverse-transmission ultrasound.  

PubMed

Here we describe the use of a 5-MHz focused transmission system to image the bone repair region and to distinguish the early healing phases in a rat osteotomy (OT) model. Twelve-month-old female rats underwent a 2-mm OT. After 6 wk of consolidation, 2-D projection images of time-of-flight, speed of sound, and ultrasound attenuation were measured in vitro. The tissue types in the OT gap region were assessed by site-matched histology sections and micro-computed tomography (?CT). In the cases investigated, OT gap regions containing fibrous tissue (group A) were found to have similar properties compared with adjacent muscle tissue, whereas regions filled with cartilage and mineralized callus tissues (group B) differed significantly. Analysis of variance revealed that the healing group had a stronger effect on acoustic parameters (F < 35) than on ?CT-based parameters (F < 22). This pilot study reports the feasibility of transverse transmission quantitative ultrasound in assessment of the onset of cartilage formation during callus formation. PMID:23830097

Rohrbach, Daniel; Preininger, Bernd; Hesse, Bernhard; Gerigk, Hinnerk; Perka, Carsten; Raum, Kay

2013-07-03

350

Risedronate increases bone mass in an early postmenopausal population: two years of treatment plus one year of follow-up.  

PubMed

This double-blind, placebo-controlled study was undertaken to determine 1) the efficacy of oral risedronate for prevention of bone loss in healthy, early postmenopausal patients with normal bone mass, 2) the effect on bone mass when treatment was stopped, and 3) the safety and tolerance of risedronate in this population. A group of 111 patients were randomized to oral placebo, risedronate 5 mg daily, or risedronate 5 mg cyclically, for 2 yr followed by 1 yr off treatment. Measurements included percentage change from baseline in lumbar spine bone mineral density (BMD) at 24 months; percentage change from baseline in BMD of the femoral neck, trochanteric region, and Ward's triangle region of the proximal femur; and changes in biochemical markers of bone turnover. After 2 yr, there was a mean increase in BMD of the lumbar spine of 1.4% from baseline and of 5.7% vs. placebo in the risedronate 5 mg daily group. There were decreases from baseline in BMD of 1.6% and 4.3% in the risedronate 5 mg cyclic and placebo groups, respectively. By the end of 24 months, trochanteric bone mass at the hip increased by 5.4% in the risedronate 5 mg daily group and by 3.3% in the risedronate 5 mg cyclic group vs. placebo. Bone mass was maintained at the femoral neck in the 2 active-treatment groups vs. a 2.4% mean loss with placebo. During the treatment-free follow-up, bone turnover increased toward baseline in both risedronate groups. By the end of that year, lumbar spine bone mass in all 3 groups was lower than at baseline. Oral risedronate was well tolerated. We conclude that risedronate (5 mg daily) increases bone mass and risedronate (5 mg cyclic) appears to prevent bone loss in early postmenopausal women with normal BMD. PMID:9467547

Mortensen, L; Charles, P; Bekker, P J; Digennaro, J; Johnston, C C

1998-02-01

351

Enhancement of murine bone marrow colony formation and L-transformation by Brucella antigen.  

PubMed Central

Brucella melitensis and Pseudomonas aeruginos antigens, in the form of heat-killed cells, enhanced serum stimulation of colony formation by mouse bone marrow progenitor cells. The antigens also enhanced colony formation in unstimulated medium. Prior sensitization of the C57BL mice by recent infection or by immunization six months earlier increased sensitivity of bone marrow cells to brucella antigen enhancement of colony formation. The immunized mice provided marrow cells more primed to colony formation than infected mice. Evidence is presented that antigen also leads to greater recovery of live brucellae from marrow cells of infected animals. This may be due both to stimulation of the marrow cells and to direct stimulation of the brucellae in those cells. L-forms of brucellae from stimulated marrow cell cultures were isolated. Some degree of stabilization of the L-form was accomplished through incorporation into the marrow culture medium of MgSO4, sucrose and penicillin G. The place in the infection process of L-forms is discussed in terms of the hypothesis that the L-form is a product of immune reactions that involve a step-wise degradation of the brucella cell wall during which the various cell-mediated immune reactions become operative and are themselves the reflection of a general stimulation by the brucellae of the hemopoietic and lymphopoietic systems.

Elberg, S S; Ralston, D J

1980-01-01

352

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

353

Assessing Early Learning through Formative Assessment: Key Issues and Considerations  

ERIC Educational Resources Information Center

|At all levels of education the assessment of learning is generally regarded as an integral part of teachers' work. For early childhood teachers, i.e., those who work with children in the age-range birth to six years, there are very particular considerations arising from the characteristics of young learners and the nature of early learning. This…

Dunphy, Elizabeth

2010-01-01

354

Early Solar Systems and the Formation of Massive Stars  

Microsoft Academic Search

The recent discovery of the 0.8 Msolar highly iron-deficient star HE0107-5240 indicates that solar systems probably form in the very early universe. We discuss some implications of this discovery. Massive stars are predicted to be more common in the early universe than at the present epoch. We describe previously unpublished calculations of massive protostars.

William K. Rose

2004-01-01

355

Early Solar Systems and the Formation of Massive Stars  

Microsoft Academic Search

The recent discovery of the 0.8 M⊙ highly iron-deficient star HE0107-5240 indicates that solar systems probably form in the very early universe. We discuss some implications of this discovery. Massive stars are predicted to be more common in the early universe than at the present epoch. We describe previously unpublished calculations of massive protostars.

William K. Rose

2004-01-01

356

Homeobox genes d11-d13 and a13 control mouse autopod cortical bone and joint formation  

PubMed Central

The molecular mechanisms that govern bone and joint formation are complex, involving an integrated network of signaling pathways and gene regulators. We investigated the role of Hox genes, which are known to specify individual segments of the skeleton, in the formation of autopod limb bones (i.e., the hands and feet) using the mouse mutant synpolydactyly homolog (spdh), which encodes a polyalanine expansion in Hoxd13. We found that no cortical bone was formed in the autopod in spdh/spdh mice; instead, these bones underwent trabecular ossification after birth. Spdh/spdh metacarpals acquired an ovoid shape and developed ectopic joints, indicating a loss of long bone characteristics and thus a transformation of metacarpals into carpal bones. The perichondrium of spdh/spdh mice showed abnormal morphology and decreased expression of Runt-related transcription factor 2 (Runx2), which was identified as a direct Hoxd13 transcriptional target. Hoxd11–/–Hoxd12–/–Hoxd13–/– triple-knockout mice and Hoxd13–/–Hoxa13+/– mice exhibited similar but less severe defects, suggesting that these Hox genes have similar and complementary functions and that the spdh allele acts as a dominant negative. This effect was shown to be due to sequestration of other polyalanine-containing transcription factors by the mutant Hoxd13 in the cytoplasm, leading to their degradation. These data indicate that Hox genes not only regulate patterning but also directly influence bone formation and the ossification pattern of bones, in part via Runx2.

Villavicencio-Lorini, Pablo; Kuss, Pia; Friedrich, Julia; Haupt, Julia; Farooq, Muhammed; Turkmen, Seval; Duboule, Denis; Hecht, Jochen; Mundlos, Stefan

2010-01-01

357

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

SciTech Connect

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

Jasty, M.; Schutzer, S.; Tepper, J.; Willett, C.; Stracher, M.A.; Harris, W.H. (Massachusetts General Hospital (USA))

1990-08-01

358

Effect of Calcium Supplementation as a High-Calcium Mineral Water on Bone Loss in Early Postmenopausal Women  

Microsoft Academic Search

.   It is generally agreed that an adequate calcium intake is necessary for the maintenance of bone health and that calcium supplementation\\u000a reduces the rate of bone loss in postmenopausal women. Mineral waters are calorie free, and some, with relatively high calcium\\u000a levels, might be significant sources of calcium. We studied the effect of mineral water in 45 early postmenopausal

C. Cepollaro; G. Orlandi; S. Gonnelli; G. Ferrucci; J. C. Arditti; D. Borracelli; E. Toti; C. Gennari

1996-01-01

359

High Habitual Calcium Intake Attenuates Bone Loss in Early Postmenopausal Chinese Women: An 18Month Follow-Up Study  

Microsoft Academic Search

This study assessed the association of habitual dietary cal- cium intake and bone loss in early postmenopausal women. Four hundred fifty-four healthy postmenopausal Chinese women were enrolled for this 18-month cohort study. The subjects were 48-62 yr of age and within 12 yr of natural menopause. Dietary intake was assessed by the food fre- quency method, and bone mass was

SUZANNE C. HO; YU-MING CHEN; JEAN L. F. WOO; SILVIA S. H. LAM

2010-01-01

360

Differential requirement for B-memory and T-memory cells in adoptive antibody formation in mouse bone marrow.  

PubMed Central

During the secondary response of mice to T-dependent antigens, antibody-producing plaque-forming cells (PFC) appear not only in peripheral lymphoid organs, but also in the bone marrow. This bone marrow antibody formation is feeble after primary immunization. The capacity of bone marrow antibody formation is dependent on the presence of antigen-specific memory cells at the moment of secondary immunization. We investigated whether hapten-primed B memory, carrier-primed T memory or both B-memory and T-memory cells are required for the adoptive PFC response in the bone marrow to T-dependent hapten-carrier conjugates. Adoptive antibody formation in the bone marrow was found after transfer of hapten-primed spleen cells, but not after transfer of carrier-primed spleen cells or virgin spleen cells. Thus, B-memory cells are obligatory for adoptive antibody formation in the bone marrow, in contrast to T-memory cells. However, T-memory cells did facilitate the bone marrow PFC response mediated by the infused B-memory cells.

Koch, G; Benner, R

1982-01-01

361

Clonal distribution of osteoprogenitor cells in cultured chick periostea: Functional relationship to bone formation  

SciTech Connect

Folded explants of periosteum from embryonic chick calvaria form bone-like tissue when grown in the presence of ascorbic acid, organic phosphate, and dexamethasone. All osteoblast-like cells in these cultures arise de novo by differentiation of osteoprogenitor cells present in the periosteum. To study the spatial and functional relationships between bone formation and osteoprogenitor cells, cultures were continuously labeled with (3H)thymidine for periods of 1-5 days. Radioautographs of serial 2-microns plastic sections stained for alkaline phosphatase (AP) showed maximal labeling of 30% of fibroblastic (AP-negative) cells by 3 days while osteogenic cells (AP-positive) exhibited over 95% labeling by 5 days. No differential shifts in labeling indices, grain count histograms of fibroblastic and osteogenic cells or numbers of AP-positive cells were observed, indicating no significant recruitment of cells from the fibroblastic to the osteogenic compartment. Despite the continuous presence of (3H)thymidine, less than 35% of both osteoblasts and osteocytes were labeled at 5 days, indicating that only one-third of the osteoprogenitor cells had cycled prior to differentiation. Spatial clustering of (3H)thymidine-labeled cells was measured by computer-assisted morphometry and application of the Poisson distribution to assess contagion. Cluster size and number of labeled cells per cluster did not vary between 1-3 days, but the number of clusters increased 20-fold between Day 1 and Day 3. Three-dimensional reconstruction from serial sections showed that clusters formed long, tubular arrays of osteogenic cells up to eight cells in length and located within 2-3 cell layers from the bone surface. Selective killing of S-phase cells with two pulse labels of high specific activity (3H)thymidine at 1 and 2 days of culture completely blocked bone formation.

McCulloch, C.A.; Fair, C.A.; Tenenbaum, H.C.; Limeback, H.; Homareau, R. (Univ. of Toronto, Ontario (Canada))

1990-08-01

362

Immunohistochemical characterization of guided bone formation by a biodegradable tissue engineering scaffold in a healing tooth socket of a rabbit model  

Microsoft Academic Search

We have developed a novel, biocompatible, biodegradable tissue engineering scaffold that has been shown to facilitate bone formation in vivo. The process of bone formation within this scaffold, however, is unknown at a molecular level. To study this process, a rabbit's four healing incisor sockets (two mandibular and two maxillar) that remain after tooth extraction were used as a bone

J. P. Fisher; Z. Lalani; N. Demian; M. E. K. Wong; A. G. Mikos

2002-01-01

363

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.  

PubMed

Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNF?, osteoclast marker receptor activator of nuclear factor-?B, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss. PMID:22436700

Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

2012-03-20

364

Relationship between renal stone formation, mitral annular calcification and bone resorption markers  

PubMed Central

BACKGROUND AND OBJECTIVES: Mitral annular calcification (MAC) is associated with osteoporosis and there is evidence of reduced bone mineral density (BMD) in patients with renal stone formation (RSF). Therefore, we designed this study to test if RSF was associated with MAC and if this association could be linked to bone resorption. METHODS: Fifty-nine patients (mean age, 41.5 years) with RSF and 40 healthy subjects (mean age, 44.2 years) underwent screening for MAC and BMD, and measuurements were taken of serum and urine electrolytes, parathyroid hormone, alkaline phosphatase and urine dypyridoline. RESULTS: MAC was diagnosed in 11 (18%) patients with RSF compared with 1 (2.5%) control (P=.01). Urine phosphorus, magnesium, sodium, potassium and chloride levels were lower (P<.001, P=.02, P<.001, P<.001 and P<.001, respectively), but serum alkaline phosphatase, calcium and potassium levels were higher (P=.008, P=.007 and P=.001, respectively) in patients with RSF versus those without RSF. None of these abnormalities were found in patients or subjects with MAC. Urine pyridoline levels were higher and T-scores were more negative (more osteopenic) in patients and subjects with MAC than in those without MAC (P=.01 and P=.004, respectively). In a multivariate analysis, only T-scores and urine dipyridoline level were predictive of MAC (P=.03 and P=.04, respectively). CONCLUSIONS: Screening for MAC and bone resorption markers in patients with RSF demonstrated a high incidence of MAC in these patients. The presence of MAC in patients with RSF was associated with bone resorption markers. This seemingly complex interrelationship between RSF, MAC and bone loss needs to be clarified in further studies.

Celik, Ahmet; Davutoglu, Vedat; Sarica, Kemal; Erturhan, Sakip; Ozer, Orhan; Sari, Ibrahim; Yilmaz, Mustafa; Baltaci, Yasemin; Akcay, Murat; Al, Behcet; Yuce, Murat; Yilmaz, Necat

2010-01-01

365

Cancer Cell Expression of Autotaxin Controls Bone Metastasis Formation in Mouse through Lysophosphatidic Acid-Dependent Activation of Osteoclasts  

PubMed Central

Background Bone metastases are highly frequent complications of breast cancers. Current bone metastasis treatments using powerful anti-resorbtive agents are only palliative indicating that factors independent of bone resorption control bone metastasis progression. Autotaxin (ATX/NPP2) is a secreted protein with both oncogenic and pro-metastatic properties. Through its lysosphospholipase D (lysoPLD) activity, ATX controls the level of lysophosphatidic acid (LPA) in the blood. Platelet-derived LPA promotes the progression of osteolytic bone metastases of breast cancer cells. We asked whether ATX was involved in the bone metastasis process. We characterized the role of ATX in osteolytic bone metastasis formation by using genetically modified breast cancer cells exploited on different osteolytic bone metastasis mouse models. Methodology/Principal Findings Intravenous injection of human breast cancer MDA-B02 cells with forced expression of ATX (MDA-B02/ATX) to inmmunodeficiency BALB/C nude mice enhanced osteolytic bone metastasis formation, as judged by increased bone loss, tumor burden, and a higher number of active osteoclasts at the metastatic site. Mouse breast cancer 4T1 cells induced the formation of osteolytic bone metastases after intracardiac injection in immunocompetent BALB/C mice. These cells expressed active ATX and silencing ATX expression inhibited the extent of osteolytic bone lesions and decreased the number of active osteoclasts at the bone metastatic site. In vitro, osteoclast differentiation was enhanced in presence of MDA-B02/ATX cell conditioned media or recombinant autotaxin that was blocked by the autotaxin inhibitor vpc8a202. In vitro, addition of LPA to active charcoal-treated serum restored the capacity of the serum to support RANK-L/MCSF-induced osteoclastogenesis. Conclusion/Significance Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a factor that stimulates directly cancer growth and metastasis, and osteoclast differentiation. Therefore, targeting the autotaxin/LPA track emerges as a potential new therapeutic approach to improve the outcome of patients with bone metastases.

David, Marion; Wannecq, Estelle; Descotes, Francoise; Jansen, Silvia; Deux, Blandine; Ribeiro, Johnny; Serre, Claire-Marie; Gres, Sandra; Bendriss-Vermare, Nathalie; Bollen, Mathieu; Saez, Simone; Aoki, Junken; Saulnier-Blache, Jean-Sebastien; Clezardin, Philippe; Peyruchaud, Olivier

2010-01-01

366

Effect of biological implant surface coatings on bone formation, applying collagen, proteoglycans, glycosaminoglycans and growth factors  

Microsoft Academic Search

Objectives  The aim of the present study was to evaluate six different implant surface coatings with respect to bone formation. Being\\u000a major structural components of the extracellular matrix, collagen, the non-collagenous components decorin\\/chondroitin sulphate\\u000a (CS) and the growth factors TGF-?1\\/BMP-4 served in different combinations as coatings of experimental titanium implants.\\u000a \\u000a \\u000a \\u000a Materials and methods  Eight miniature pigs received each six implants in the

Bernd Stadlinger; Eckart Pilling; Ronald Mai; Susanne Bierbaum; Ricardo Berhardt; Dieter Scharnweber; Uwe Eckelt

2008-01-01

367

The relationship between inflammation and new bone formation in patients with ankylosing spondylitis  

PubMed Central

Introduction Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Methods Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondylitis patients treated with anti-tumour necrosis factor (anti-TNF) agents at baseline and after 2 years were analysed for syndesmophyte formation at vertebral edges with or without inflammatory lesions at baseline. Results Overall, 922 vertebral edges at the cervical and lumbar spine were analysed. At baseline, the proportion of vertebral edges with and without inflammation (magnetic resonance imaging) that showed structural changes (conventional radiographs) was similar (in total, 16.6% of all vertebral edges in 71.4% of patients). From the perspective of syndesmophyte formation (n = 26, 2.9%) after 2 years, there were more vertebral edges without (62%) than with (38%) inflammation at baseline (P = 0.03). From the perspective of spinal inflammation at baseline (n = 153 vertebral edges), more syndesmophytes developed at vertebral edges with (6.5%) than without (2.1%) inflammation (P = 0.002, odds ratio 3.3, 95% confidence interval 1.5 to 7.4). Inflammation persisted in 31% of the initially inflamed vertebral edges (n = 132), and new lesions developed in 8% of the vertebral edges without inflammation at baseline (n = 410). From the perspective of spinal inflammation after 2 years (n = 72 vertebral edges), 5.6% of the vertebral edges showed syndesmophyte development in contrast to 1.9% of the vertebral edges with new syndesmophytes without inflammation (P = 0.06). Conclusions These findings obtained in patients treated with anti-TNF agents suggest linkage and some dissociation of inflammation and new bone formation in ankylosing spondylitis. Although syndesmophytes were also found to develop at sites where no inflammation had been seen by magnetic resonance imaging at baseline, it was more likely that syndesmophytes developed in inflamed vertebral edges. More effective suppression of spinal inflammation may be required to inhibit structural damage in ankylosing spondylitis.

Baraliakos, Xenofon; Listing, Joachim; Rudwaleit, Martin; Sieper, Joachim; Braun, Juergen

2008-01-01

368

Early Stages of Golgi Vesicle and Tubule Formation Require Diacylglycerol  

PubMed Central

We have investigated the role for diacylglycerol (DAG) in membrane bud formation in the Golgi apparatus. Addition of propranolol to specifically inhibit phosphatidate phosphohydrolase (PAP), an enzyme responsible for converting phosphatidic acid into DAG, effectively prevents formation of membrane buds. The effect of PAP inhibition on Golgi membranes is rapid and occurs within 3 min. Removal of the PAP inhibitor then results in a rapid burst of buds, vesicles, and tubules that peaks within 2 min. The inability to form buds in the presence of propranolol does not appear to be correlated with a loss of ARFGAP1 from Golgi membranes, as knockdown of ARFGAP1 by RNA interference has little or no effect on actual bud formation. Rather, knockdown of ARFGAP1 results in an increase in membrane buds and a decrease of vesicles and tubules suggesting it functions in the late stages of scission. How DAG promotes bud formation is discussed.

Asp, Lennart; Kartberg, Fredrik; Fernandez-Rodriguez, Julia; Smedh, Maria; Elsner, Markus; Laporte, Frederic; Barcena, Montserrat; Jansen, Karen A.; Valentijn, Jack A.; Koster, Abraham J.; Bergeron, John J.M.

2009-01-01

369

Angiogenic factor-enriched platelet-rich plasma enhances in vivo bone formation around alloplastic graft material  

PubMed Central

PURPOSE Although most researchers agree that platelet-rich plasma (PRP) is a good source of autogenous growth factors, its effect on bone regeneration is still controversial. The purpose of this study was to evaluate whether increasing angiogenic factors in the human PRP to enhance new bone formation through rapid angiogenesis. MATERIAL AND METHODS In vitro, the human platelets were activated with application of shear stress, 20 µg/ml collagen, 2 mM CaCl2 and 10U thrombin/1 × 109 platelets. Level of vascular endothelial growth factor (VEGF) and platelet microparticle (PMP) in the activated platelets were checked. In the animal study, human angiogenic factors-enriched PRP was tested in 28 athymic rat's cranial critical bone defects with ?-TCP. Angiogenesis and osteogenesis were evaluated by laser Doppler perfusion imaging, histology, dual energy X-ray densinometry, and micro-computed tomography. RESULTS In vitro, this human angiogenic factors-enriched PRP resulted in better cellular proliferation and osteogenic differentiation. In vivo, increasing angiogenic potential of the PRP showed significantly higher blood perfusion around the defect and enhanced new bone formation around acellular bone graft material. CONCLUSION Angiogenic factor-enriched PRP leads to faster and more extensive new bone formation in the critical size bone defect. The results implicate that rapid angiogenesis in the initial healing period by PRP could be supposed as a way to overcome short term effect of the rapid angiogenesis.

Kim, Eun-Seok; Kim, Jae-Jin

2010-01-01

370

Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.  

PubMed

myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. PMID:20818642

Dai, Zhijie; Chung, Sookja K; Miao, Dengshun; Lau, Kam S; Chan, Alfred W H; Kung, Annie W C

2011-03-01

371

ATP and UTP at low concentrations strongly inhibit bone formation by osteoblasts: A novel role for the P2Y2 receptor in bone remodeling  

Microsoft Academic Search

There is increasing evidence that extracellular nucleotides act on bone cells via multiple P2 receptors. The naturally-occurring ligand ATP is a potent agonist at all receptor subtypes, whereas ADP and UTP only act at specific receptor subtypes. We have reported that the formation and resorptive activity of rodent osteoclasts are stimulated powerfully by both extracellular ATP and its first degradation

Astrid Hoebertz; Siva Mahendran; Geoffrey Burnstock; Timothy R. Arnett

2002-01-01

372

BMP-2 gene modified canine bMSCs promote ectopic bone formation mediated by a nonviral PEI derivative  

PubMed Central

The study was to explore the effects of BMP-2 gene modified canine bone marrow stromal cells (bMSCs) mediated by a nonviral PEI derivative (GenEscort™ II) in promoting bone formation in vitro and in vivo. Canine bMSCs were cultured and transfected with plasmids containing bone morphogenetic protein-2 gene (pBMP-2) or enhanced green fluorescent protein gene (pEGFP). Gene transfection conditions were initially optimized by varying GenEscort™ II/plasmid ratios. Osteogenic differentiation of gene modified bMSCs was investigated via alkaline phosphatase (ALP) activity analysis and real-time quantitative PCR (RT-qPCR) analysis in vitro. The bone formation ability of pBMP-2 transfected bMSCs combined with apatite-coated silk scaffolds (mSS) was explored and compared with pEGFP transfected bMSCs/mSS or untreated bMSCs/mSS at 8, 12 weeks after operation. Results showed that gene transfection efficiency reached up to 36.67 ± 4.12% as demonstrated by EGFP expression. ALP staining and activity assay were stronger with pBMP-2 gene transfection, and the mRNA expression of BMP-2, bone sialoprotein (BSP), Runt-related transcription factor 2 (Runx-2) and osteopontin (OPN) up-regulated in bMSCs 3, 6, 9 days in pBMP-2 group. Besides, the tissue-engineered bone complex with pBMP-2 modified bMSCs achieved significantly increased de novo bone formation compared with control groups (P<0.01). We conclude that pBMP-2 transfection mediated by GenEscort™ II could enhance the osteogenic differentiation of canine bMSCs and promote the ectopic new bone formation in nude mice. GenEscort™ II mediated pBMP-2 gene transfer appears to be a safe and effective nonviral method for gene enhanced bone tissue engineering.

Lu, Kaige; Zeng, Dengliang; Zhang, Yilin; Xia, Lunguo; Xu, Ling; Kaplan, David L.; Jiang, Xinquan; Zhang, Fuqiang

2012-01-01

373

Unusual bone formation in the anterior rim of foramen magnum: cause, effect and treatment.  

PubMed

A rare case of proatlas segmental abnormality resulting in a bony mass in the anterior rim of the foramen magnum is studied. Case report of a 19-year-old female showed a progressive weakness of all four limbs for about 3 years. When admitted she could not perform any useful activities by herself. Investigations revealed an unusual bone growth in the region of the anterior rim of foramen magnum that resulted in severe cord compression. The abnormal bone formation involved the lower end of clivus, the tip of the odontoid process and the posterior arch of the atlas. Dynamic imaging did not reveal any clear evidence of instability. Following transoral decompression and posterior fixation, the patient showed dramatic and lasting clinical recovery. Conclusions were drawn as follows. Anomalies of the most caudal part of the occipital sclerotomes due to the failure of proatlas segmentation can be the cause of an abnormal bone mass in the anterior rim of foramen magnum. Transoral decompression, followed by posterior atlantoaxial fixation, results in neurological recovery and provides lasting cure from the problem. PMID:20033741

Goel, Atul; Shah, Abhidha

2009-12-24

374

Complexation and Sequestration of BMP-2 from an ECM Mimetic Hyaluronan Gel for Improved Bone Formation.  

PubMed

Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs) dermatan sulfate (DS) or heparin (HP), prior to loading it into a hyaluronic acid (HA) hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG. PMID:24167632

Kisiel, Marta; Klar, Agnieszka S; Ventura, Manuela; Buijs, Jos; Mafina, Marc-Krystelle; Cool, Simon M; Hilborn, Jöns

2013-10-22

375

Complexation and Sequestration of BMP-2 from an ECM Mimetic Hyaluronan Gel for Improved Bone Formation  

PubMed Central

Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs) dermatan sulfate (DS) or heparin (HP), prior to loading it into a hyaluronic acid (HA) hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG.

Kisiel, Marta; Klar, Agnieszka S.; Ventura, Manuela; Buijs, Jos; Mafina, Marc-Krystelle; Cool, Simon M.; Hilborn, Jons

2013-01-01

376

Perinatal maternal dietary supplementation of ?3-fatty acids transiently affects bone marrow microenvironment, osteoblast and osteoclast formation, and bone mass in male offspring.  

PubMed

It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with ?3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-?B ligand, TNF-?, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health. PMID:22374977

Fong, Laura; Muhlhausler, Beverly S; Gibson, Robert A; Xian, Cory J

2012-02-28

377

PTHrP 1-141 and 1-86 Increase In Vitro Bone Formation  

PubMed Central

Background Parathyroid hormone-related protein (PTHrP) has anabolic effects in bone, which has led to the clinical use of N-terminal fragments of PTHrP and PTH. Since 10-20% of fractures demonstrate healing complications and osteoporosis continues to be a debilitating disease, the development of bone-forming agents is of utmost importance. Due to evidence that regions of PTHrP other than the N-terminus may have bone-forming effects, this study was designed to compare the effects of full-length PTHrP 1-141 to N-terminal PTHrP 1-86 on in vitro bone formation. Materials and methods MC3T3-E1 pre-osteoblasts were treated once every 6 days for 36 days with 5, 25, and 50 pM of PTHrP 1-141 or 1-86 for 1 or 24 hours. Cells were also treated after blocking the N-terminus, the nuclear localization sequence (NLS), and the C-terminus of PTHrP, individually and in combination. Area of mineralization, alkaline phosphatase (ALP), and osteocalcin (OCN) were measured. Results PTHrP 1-141 and 1-86 increased mineralization after 24-hr treatments, but not 1-hr. PTHrP 1-141 was more potent than 1-86. Treatment with PTHrP 1-141 for 24-hr, but not 1-86, resulted in a concentration-dependent increase in ALP, with no effect after 1-hr. Exposure to both peptides for 1- or 24-hrs induced a concentration-dependent increase in OCN, with 24-hr exceeding 1-hr. Antibody blocking revealed that the NLS and C-terminus are anabolic. Conclusions Both PTHrP 1-141 and 1-86 increased in vitro bone formation; however, PTHrP 1-141 was more effective. The NLS and C-terminus have anabolic effects distinct from the N-terminus. This demonstrates the advantage of PTHrP 1-141 as a skeletal anabolic agent.

Hildreth, Blake Eason; Werbeck, Jillian L.; Thudi, Nandu K.; Deng, Xiyun; Rosol, Thomas J.; Toribio, Ramiro E.

2010-01-01