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1

576. Hypoxic Adipocytes Support Early Heterotopic Bone Formation  

Microsoft Academic Search

The factors contributing to heterotopic ossification, the formation of bone in abnormal soft-tissue locations, are beginning to emerge, but very little is known about the microenvironmental conditions that promote this often devastating disease. Using a murine model in which endochondral bone formation is triggered in muscle by bone morphogenetic protein 2 (BMP2), we studied the cellular and biochemical changes near

Elizabeth A. Olmsted-Davis; Francis H. Gannon; Zbigniew Gugala; John A. Hipp; Christine Foultier-Dilling; Michael H. Heggeness; Alan R. Davis

2006-01-01

2

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

PubMed

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

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

2015-02-01

3

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

PubMed Central

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

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

2014-01-01

4

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

2012-06-01

5

Bone substitutes and bone formation  

Microsoft Academic Search

Summary  \\u000a Prompted by severe problems in autogeneic and allogeneic bone transplantation, intensive efforts were made to find sufficient\\u000a substitutes. A main demand on these materials, especially in healing of osseous defects, is to achieve results comparable\\u000a to those of auto- or allografts. These must be related to their biomechanical and particularly to their biological properties,\\u000a i. e. the ability to

H. Stützle; K. Hallfeldt; H. Mandelkow; S. Keßler; L. Schweiberer

1998-01-01

6

Gap junction proteins exhibit early and specific expression during intramembranous bone formation in the developing chick mandible  

Microsoft Academic Search

The spatial and temporal expression of three closely related members of the connexin family of gap junction proteins (connexin42, Cx42; connexin43, Cx43; and connexin45, Cx45) was evaluated during bone formation in the mandibular process of the chick embryo. Mandibles of chick embryos from Hamburger and Hamilton stage 25 (approximately 5 days) through 19 days of development were dissected, serially sectioned

R. Minkoff; V. R. Rundus; S. B. Parker; E. L. Hertzberg; J. G. Laing; E. C. Beyer

1994-01-01

7

Peripheral Leptin Regulates Bone Formation  

PubMed Central

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

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

2012-01-01

8

Effects of ipriflavone on perialveolar bone formation.  

PubMed

The effect of ipriflavone (IP), a synthetic isoflavonoid derivative, on in vivo bone formation was studied in rat perialveolar bone by surgically producing a hole in the mandibular bone. The holes were filled either with powdered IP or with compounds containing no osteoinductive properties such as biostite and Htr (hard tissue replacement). In control animals, the holes were left to heal spontaneously. The animals were killed 3, 28, and 40 days after surgery and a detailed morphological and morphometric study was performed on the perialveolar bone surrounding the wounds. Three days after surgery (inflammatory phase) the bone wounds were occupied by hemorragic and inflammatory cells in both the untreated and IP-treated bone defects. Twenty-eight days after surgery, bone formation was evident with new bone spiculae particularly concentrated in the area of the bone lesion closest to the adjacent periodontal ligament. Morphometric measurements of the areas occupied by new bone showed that the synthesis of perialveolar bone was significantly stimulated by IP. The repair of the bone defects by new bone formation progressed by day 40, but only in the presence of IP were the original holes almost completely repaired. Conversely, biostite and Htr did not influence promotion of new bone formation. In conclusion, the results of the present study are consistent with a role of IP in stimulating osteogenesis and suggest that this compound could represent a potential therapeutic tool to promote repair of injured perialveolar bone. PMID:9744990

Martini, M; Formigli, L; Tonelli, P; Giannelli, M; Amunni, F; Naldi, D; Brandi, M L; Zecchi Orlandini, S; Orlandini, G E

1998-10-01

9

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). (ML)

Canalis, Ernesto

1985-01-01

10

Bone formation in axial spondyloarthritis.  

PubMed

The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage. PMID:25488783

Lories, Rik J; Haroon, Nigil

2014-10-01

11

Early radiographic changes in radiation bone injury  

SciTech Connect

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

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

1986-06-01

12

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

13

Mechanisms of osteoclast-dependent bone formation  

PubMed Central

Should we believe that osteoclasts are only involved in bone resorption? What about their contribution to bone formation? In this article I will review evidence that bone formation can be regulated by osteoclasts. Why is this? Likely because in the physiologic condition of bone remodeling, bone resorption and formation are balanced, and there is no better way to control this equilibrium than through a concerted action between the two cell types. Although the influence of osteoblasts on osteoclastic bone resorption is well documented and consolidated over time, what osteoclasts do to regulate osteoblast activity is still matter of intense investigation. The original hypothesis that all is in the osteoblast-seeking factors stored in the bone matrix, released and activated during bone resorption, is now being challenged by several studies, suggesting that osteoclasts are also capable of producing ‘clastokines' that regulate osteoblast performance. Indeed, several of them have been demonstrated to orchestrate osteoclast–osteoblast activities. However, we are probably still at the dawn of a new era, and future work will tell us whether any of these clastokines can be exploited to stimulate bone formation and rebalance bone remodeling in skeletal diseases. PMID:24422142

Teti, Anna

2013-01-01

14

Space flight and bone formation  

NASA Technical Reports Server (NTRS)

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

Doty, St B.

2004-01-01

15

The transcriptional cofactor Lbh regulates angiogenesis and endochondral bone formation during fetal bone development.  

PubMed

Lbh is thought to act as a transcriptional cofactor and is highly conserved among species. Here we show that Lbh is expressed in chondrocytes, cells of the perichondrium, and the primary spongiosa in fetal growth plates of mice and chickens. Lbh overexpression in chick wings, using the RCAS-retroviral vector strategy, results in shortened skeletal elements and delayed hypertrophic chondrocyte maturation and bone formation. Additionally, osteoclast and endothelial cell invasion are delayed in the Lbh-overexpressing bones. Finally, we find a dramatic suppression of Runx2 and VEGF mRNAs in chondrocytes and osteoblasts that overexpress Lbh. Strikingly, this abnormal bone development in infected limbs can be rescued by concurrent overexpression of Runx2. These results suggest that during endochondral bone formation, Lbh may negatively regulate vascular invasion and formation of the early ossification center at least in part by interfering with Runx2 and/or VEGF expression. PMID:19607824

Conen, K L; Nishimori, S; Provot, S; Kronenberg, H M

2009-09-15

16

Prevention of heterotopic bone formation with early post operative irradiation in high risk patients undergoing total hip arthroplasty: comparison of 10. 00 Gy vs 20. 00 Gy schedules  

SciTech Connect

Prior studies have demonstrated the effectiveness of postoperative radiation therapy (RT) to the hip area following total hip replacement (THR) surgery in preventing the development of heterotopic bone formation in patients considered to be at high risk for development of this complication. Previously, patients received 20.00 Gy in 10 fractions (fx) over 2 weeks, beginning as soon postop as medically feasible (usually post-op day 2). In an effort to reduce hospital stay and risk of secondary malignancy, a prospective treatment program was initiated April 1982 using a reduced dose of 10.00 Gy in 5 fx over 5-7 days. As of February 1984, 46 consecutive hips determined to be at high risk were treated with this reduced dose. Prior studies have demonstrated that heterotopic bone is always radiographically evident by 8 weeks. Of the 46 hips, 41 had been evaluated with the minimum required 8 week follow-up X ray. Twenty-five of these hips, 61%, had a mean long term follow-up of 12 months. It historical control group, consisting of 54 consecutive high risk post-THR's, was shown to have a 68.5% incidence of heterotopic bone. The 20.00 Gy group, when RT was started by post-op day 5, demonstrated a 3.2% incidence, compared to 4.9% in the 10.00 Gy group. Complication rates were also comparable in the two RT groups, 19.4% and 7.3% respectively; 10.00 Gy is apparently as effective as 20.00 Gy in preventing heterotopic bone formation in high risk post-THR patients.

Anthony, P.; Keys, H.; Evarts, C.M.; Rubin, P.; Lush, C.

1987-03-01

17

Effect of distraction frequency on bone formation during bone lengthening: a study in chickens.  

PubMed

We compared the effects of two distraction frequencies on bone formation during tibial lengthening by evaluating radiographs, bone mineral density, and histological findings. In 15 mature White Leghorn chickens, both tibiae were distracted at a rate of 0.75 mm/day for 10 days. The distraction frequency was 2 steps (0.375 mm/12 hour) by hand on the right side and 120 steps (0.00625 mm/12 min) by autodistractor on the left. Serial radiographs showed faster bone formation on the 120-step side than on the 2-step side. Bone mineral density on the 120-step side was also higher than that on the 2-step side at all times. On the 2-step side, endochondral ossification was marked in the early stage of distraction; then intramembranous ossification became the main mechanism of bone formation. On the 120-step side, however, intramembranous bone formation predominated throughout the study. Our findings support the contention that, at least in skeletally mature chickens, an increase in the distraction frequency improves osteogenesis during bone lengthening. PMID:14763703

Mizuta, Hiroshi; Nakamura, Eiichi; Mizumoto, Yoshihiko; Kudo, Satoshi; Takagi, Katsumasa

2003-12-01

18

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

19

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. PMID:21549864

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

2011-01-01

20

Dexamethsone suppresses bone formation via the osteoclast.  

PubMed

Glucocorticoids are central to treating inflammatory and immune disorders. These steroids, however, profoundly impact the skeleton, particularly when administered for prolonged periods. In fact, high-dose glucocorticoid therapy is almost universally associated with bone loss, prompting among the most common forms of crippling osteoporosis. Despite the frequency and severity of glucocorticoid-induced osteoporosis, its treatment is less than satisfactory, suggesting that its pathogenesis is incompletely understood. Net bone mass represents the relative activities of osteoblasts and osteoclasts and there is little question that glucocorticoids suppress the bone-forming cells, in vivo, via a process involving accelerated apoptosis (Weinstein 2001; Weinstein, Jilka, Parfitt, et al. 1998). Surprisingly, however, addition of glucocorticoids to cultures of osteoprogenitor cells actually increases their capacity to form mineralized bone nodules (Aubin 1999; Purpura, Aubin, and Zandstra 2004). This paradox raises the possibility that glucocorticoid suppression of bone formation, in vivo, reflects, at least in part, the steroid's targeting intermediary cells, which in turn inhibit the osteoblast. Bone remodeling is an ever-occuring event in mammals which is characterized by tethering of osteoclast and osteoblast function. The process is initiated by osteoclasts (OCs) resorbing a packet of bone, which in turn leads to osteoblasts being recruited to the site of resorption. This process establishes that osteoclastic bone resorption, in some manner, promotes osteoblastic bone formation at the same location. Consequently, pathologically or pharmacologically inhibited resorption eventuates in arrested osteoblast activity. PMID:17966386

Kim, Hyun-Ju; Zhao, Haibo; Kitaura, Hideki; Bhattacharyya, Sandip; Brewer, Judson A; Muglia, Louis J; Ross, F Patrick; Teitelbaum, Steven L

2007-01-01

21

Metallic materials stimulating bone formation.  

PubMed

Metallic materials implanted into bone defects are generally encapsulated by a fibrous tissue. Some metallic materials such as titanium and tantalum, however, have been revealed to bond to the living bone without forming the fibrous tissue, when they were subjected to NaOH solution and heat treatments. Thus treated metals form bone tissue around them even in muscle, when they take a porous form. This kind of osteoconductive and osteoinductive properties are attributed to sodium titanate or tantalate layer on their surfaces formed by the NaOH and heat treatments. These layers induce the deposition of bonelike apatite on the surface of the metals in the living body. This kind of bioactive metals are useful as bone substitutes even highly loaded portions, such as hip joint, spine and tooth root. PMID:15468833

Kokubo, T

2004-05-01

22

Systemic mesenchymal stem cell administration enhances bone formation in fracture repair but not load-induced bone formation.  

PubMed

Mesenchymal stem cells (MSC) were shown to support bone regeneration, when they were locally transplanted into poorly healing fractures. The benefit of systemic MSC transplantation is currently less evident. There is consensus that systemically applied MSC are recruited to the site of injury, but it is debated whether they actually support bone formation. Furthermore, the question arises as to whether circulating MSC are recruited only in case of injury or whether they also participate in mechanically induced bone formation. To answer these questions we injected green fluorescent protein (GFP)-labelled MSC into C57BL/6J mice, which were subjected either to a femur osteotomy or to non-invasive mechanical ulna loading to induce bone formation. We detected GFP-labelled MSC in the early (day 10) and late fracture callus (day 21) by immunohistochemistry. Stromal cell-derived factor 1 (SDF-1 or CXCL-12), a key chemokine for stem cell attraction, was strongly expressed by virtually all cells near the osteotomy - indicating that SDF-1 may mediate cell migration to the site of injury. We found no differences in SDF-1 expression between the groups. Micro-computed tomography (µCT) revealed significantly more bone in the callus of the MSC treated mice compared to untreated controls. The bending stiffness of callus was not significantly altered after MSC-application. In contrast, we failed to detect GFP-labelled MSC in the ulna after non-invasive mechanical loading. Histomorphometry and µCT revealed a significant load-induced increase in bone formation; however, no further increase was found after MSC administration. Concluding, our results suggest that systemically administered MSC are recruited and support bone formation only in case of injury but not in mechanically induced bone formation. PMID:25552426

Rapp, A E; Bindl, R; Heilmann, A; Erbacher, A; Müller, I; Brenner, R E; Ignatius, A

2015-01-01

23

Hypothalamic Y2 receptors regulate bone formation  

PubMed Central

Neuropeptide Y (NPY) is a downstream modulator of leptin action, possibly at the level of the arcuate nucleus where NPY neurons are known to express both leptin receptors and Y2 receptors. In addition to the well-described role of NPY and leptin in energy balance and obesity, intracerebroventricular administration of NPY or leptin also causes bone loss. Here we show that Y2 receptor–deficient mice have a twofold increase in trabecular bone volume as well as greater trabecular number and thickness compared with control mice. We also demonstrate that central Y2 receptors are crucial for this process, since selective deletion of hypothalamic Y2 receptors in mature conditional Y2 knockout mice results in an identical increase in trabecular bone volume within 5 weeks. This hypothalamus-specific Y2 receptor deletion stimulates osteoblast activity and increases the rate of bone mineralization and formation, with no effect on osteoblast or osteoclast surface measurements. The lack of any changes in plasma total calcium, leptinemia, or hypothalamo-pituitary-corticotropic, -thyrotropic, -somatotropic, or -gonadotropic output suggests that Y2 receptors do not modulate bone formation by humoral mechanisms, and that alteration of autonomic function through hypothalamic Y2 receptors may play a key role in a major central regulatory circuit of bone formation. PMID:11927618

Baldock, Paul A.; Sainsbury, Amanda; Couzens, Michelle; Enriquez, Ronaldo F.; Thomas, Gethin P.; Gardiner, Edith M.; Herzog, Herbert

2002-01-01

24

Early Stage of Galaxy Formation  

E-print Network

We discuss on the early stage of galaxy formation based on recent deep surveys for very high-redshift galaxies, mostly beyond redshift of 6. These galaxies are observed to be strong Lyman$\\alpha$ emitters, indicating bursts of massive star formation in them. The fraction of such star-forming system appears to increase with increasing redshift. On the other hand, the star formation rate density derived from Lyman$\\alpha$ emitters tends to decrease with increasing redshift. It is thus suggested that the major epoch of initial starbursts may occur around $z \\sim$ 6 -- 7. In order to understand the early stage of galaxy formation, new surveys for galaxies beyond redshift of 7 will be important in near future.

Y. Taniguchi; T. Nagao; M. Ajiki; Y. Shioya; S. S. Sasaki; T. Murayama

2005-10-20

25

Early bone formation around immediately loaded FBR-coated implants after 8, 10 and 12 weeks: a human histologic evaluation of three retrieved implants.  

PubMed

The surface characteristics of dental implants play an important role in the osseointegration process. Over the years implant surfaces have been subjected to different treatments, including turning, plasma spraying, coating, sand blasting, acid etching, and anodization. FBR coating is a fully resorbable calcium phosphate (CaP) coating made of brushite, obtained by electrochemical deposition on titanium plasma-sprayed (TPS) implants; this bioactive layer may be totally resorbable in 6-12 weeks and once the FBR coating has been resorbed, the newly formed bone is in contact with the roughness of the TPS surface. Human biopsy of immediately-loaded implants is certainly the most definitive means of determining the occurrence of osseointegration. In this case series the histologic and histomorphometric features of the bone-implant interface are analyzed and discussed in 3 immediately restored implants, retrieved from human subjects at 8, 10 and 12 weeks, respectively. All 3 implants were osseointegrated, with a bone to implant contact (BIC) ranging from 54.4% to 70.1%. The FBR coating was resorbed and replaced by new bone. Osteoconduction was especially noticeable between the implant threads, where the pristine bone was removed during implant bed preparation. The results suggest that the resorption window of 6-12 weeks for the CaP coating seems to be confirmed at least in the human mandible, and that immediately loaded FBR-coated implants placed in the posterior mandible can achieve osseointegration within 6-12 weeks of loading. PMID:21471943

Malchiodi, L; Ghensi, P; Cucchi, A; Trisi, P; Szmukler-Moncler, S; Corrocher, G; Gerosa, R

2011-04-01

26

Uranium inhibits bone formation in physiologic alveolar bone modeling and remodeling  

SciTech Connect

The toxic effect of uranium (U) on bone modeling and remodeling was studied by performing histomorphometric measurements in the periodontal cortical bone of rats. Two different single intraperitoneal doses of uranyl nitrate (238U) were administered to two sets of rats respectively (2 and 0.8 mg/kg body wt). Rats treated with the first dose were killed 14 days postinjection (PI) and those treated with the second were killed 14, 30, and 60 days PI. The results revealed a decrease in bone formation in rats treated with uranium. On the remodeling side the decrease in bone formation was coupled to an increase in bone resorption on the 14th day PI. On the modeling side no bone resorption was observed and the decrease in bone formation was linked to an increase in resting bone zones. Bone formation depression as a key event in U intoxication is stressed.

Ubios, A.M.; Guglielmotti, M.B.; Steimetz, T.; Cabrini, R.L. (Univ. of Buenos Aires (Argentina))

1991-02-01

27

Bone Mineral and Predictors of Bone Mass in White, Hispanic, and Asian Early Pubertal Girls  

Microsoft Academic Search

Differences in bone among racial\\/ethnic groups may be explained by differences in body size and shape. Previous studies have\\u000a not completely explained differences among white, Asian, and Hispanic groups during growth. To determine racial\\/ethnic differences\\u000a and predictors of bone mass in early pubertal girls, we measured bone mineral content (BMC) in white, Hispanic, and Asian\\u000a sixth-grade girls across six states

C. M. Weaver; L. D. McCabe; G. P. McCabe; R. Novotny; M. Van Loan; S. Going; V. Matkovic; C. Boushey; D. A. Savaiano

2007-01-01

28

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

PubMed Central

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 bone with high accuracy (p < 10-6) and a sensitivity that was superior to the sensitivity of clinical monitoring (92% and 75% respectively). Conclusion When performing bone scintigraphy during the first three postoperative days, it not only helps to detect complications with high accuracy, as described in earlier studies, but it is also an additional reliable monitoring tool to decide whether or not microvascular revision surgery should be performed. Bone scans were especially useful in buried free flaps where early postoperative monitoring depended exclusively on scans. According to our experience, we recommend bone scans as soon as possible after surgery and immediately in cases suspicious of vascularized bone graft failure. PMID:17448223

Schuepbach, Jonas; Dassonville, Olivier; Poissonnet, Gilles; Demard, Francois

2007-01-01

29

Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function  

Microsoft Academic Search

Surface reactivity is one of the common characteristics of bone bioactive ceramics. It contributes to their bone bonding ability and their enhancing effect on bone tissue formation. During implantation, reactions occur at the material–tissue interface that lead to time-dependent changes in the surface characteristics of the implant material and the tissues at the interface. This review describes some of the

P Ducheyne; Q Qiu

1999-01-01

30

The impact of skeletal unloading on bone formation  

NASA Technical Reports Server (NTRS)

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

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

2003-01-01

31

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

32

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

33

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

PubMed

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

Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

2014-09-01

34

Brief Review of Models of Ectopic Bone Formation  

PubMed Central

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

2012-01-01

35

Leptin regulates bone formation via the sympathetic nervous system  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

36

Deficient reconstitution of early progenitors after allogeneic bone marrow transplantation  

Microsoft Academic Search

Allogeneic bone marrow transplant recipients maintain normal peripheral blood counts long term, suggesting durable support from engrafted stem cells. In order to investigate late hemopoietic reconstitution at the level of committed and early progenitors (LTC-IC), we studied 64 long-term survivors at a median interval of 6 years (range: 2–20) after allogeneic bone marrow transplant. CFU-GM and BFU-E numbers did not

M Podestà; G Piaggio; F Frassoni; A Pitto; N Mordini; S Bregante; A Valeriani; A Bacigalupo

1997-01-01

37

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

SciTech Connect

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

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

2011-08-01

38

Demineralized Bone Matrix: Maximizing New Bone Formation for Successful Bone Implantation  

Microsoft Academic Search

\\u000a The bone scaffold formed by ground cortical bone and cancel-lous chips creates the favorable environment required for bone-forming\\u000a cells to be able to generate new bone; this property is called osteoconductivity. The demineralization of bone matrix exposes bone morphogenetic proteins (BMPs) and other bone growth promoting factors.\\u000a Because of this, deminer-alized bone matrix (DBM) not only provides a scaffold for

Lloyd Wolfinbarger Jr; Liisa M. Eisenlohr; Katrina Ruth

39

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

40

Impaired Bone Formation in Pdia3 Deficient Mice  

PubMed Central

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

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

2014-01-01

41

The circadian modulation of leptin-controlled bone formation  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

42

Bone Density and Brain Atrophy in Early Alzheimer Disease  

PubMed Central

Studies suggest a link between bone loss and Alzheimer’s disease. To examine bone mineral density (BMD) in early Alzheimer’s disease (AD) and its relationship to brain structure and cognition we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 ± 0.13) compared to the non-demented control group (1.16 ± 0.12, p=0.02), independent of age, sex, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b=0.18, p=0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b=0.15, p=0.04], delayed logical memory [b=0.16, p=0.02], and the selective reminding task, free recall [b=0.18, p=0.009]). Bone mineral density is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early Alzheimer’s disease. PMID:19661621

Loskutova, Natalia; Honea, Robyn A.; Vidoni, Eric D.; Brooks, William M.; Burns, Jeffrey M.

2009-01-01

43

[Processing of ceramiclike xenogeneic bone and experimental study of its bone formation from composite graft combined with bone marrow].  

PubMed

Ceramiclike xenogeneic bone (CXB) was obtained from the fresh bone of pig ribs being treated by physical and chemical methods to deprive of its organic substance. The CXB possessed the same natural porous network system as that of the human. The CXB was cultured with the bone marrow stromal cells of rabit. When the marrow cells had integrated with the CXB, thus a new material was obtained. (CXB-BM), and was implanted sacro-spinal muscle of rabbit. The specimens were observed under phase microscope, light microscope and electronic scanning microscope. The results showed that: at the 2nd week after the implantation of CBX-BM composite material there began the new bone formation, and the rate of bone formation was increased with time. There was evident new bone formation after 24 weeks. The process of the new bone formation were quite similar to the composite graft of HAP red autogenous and marrow, but the former degraded faster and formed typical cancellous structure earlier. There was no new bone formation when CXB was implanted alone in the control. Both the mechanism of osteogenetic potential and its clinical application were discussed. PMID:10374603

Li, Y; Zeng, C; Wang, H

1998-03-01

44

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

PubMed

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

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

2012-06-01

45

High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur  

Microsoft Academic Search

.  ?Low-energy laser irradiation has positive effects on bone fracture healing, osteoblast proliferation, bone nodule formation,\\u000a and alkaline phosphatase activity. However, the mechanism by which low-energy laser irradiation affects bone is not clearly\\u000a known. It was recently found that light at a low radiation dosage is absorbed by intracellular chromophores. High-intensity\\u000a pulsed laser irradiation can produce acoustic waves in the target

Tadashi Ninomiya; Yuuichi Miyamoto; Taku Ito; Atsushi Yamashita; Masayoshi Wakita; Tsuyoshi Nishisaka

2003-01-01

46

Dissolution behavior and early bone apposition of calcium phosphate-coated machined implants  

PubMed Central

Purpose Calcium phosphate (CaP)-coated implants promote osseointegration and survival rate. The aim of this study was to (1) analyze the dissolution behavior of the residual CaP particles of removed implants and (2) evaluate bone apposition of CaP-coated machined surface implants at the early healing phase. Methods Mandibular premolars were extracted from five dogs. After eight weeks, the implants were placed according to drilling protocols: a nonmobile implant (NI) group and rotational implant (RI) group. For CaP dissolution behavior analysis, 8 implants were removed after 0, 1, 2, and 4 weeks. The surface morphology and deposition of the coatings were observed. For bone apposition analysis, block sections were obtained after 1-, 2-, and 4-week healing periods and the specimens were analyzed. Results Calcium and phosphorus were detected in the implants that were removed immediately after insertion, and the other implants were composed mainly of titanium. There were no notable differences between the NI and RI groups in terms of the healing process. The bone-to-implant contact and bone density in the RI group showed a remarkable increase after 2 weeks of healing. Conclusions It can be speculated that the CaP coating dissolves early in the healing phase and chemically induces early bone formation regardless of the primary stability. PMID:24455442

Hwang, Ji-Wan; Lee, Eun-Ung; Lee, Jung-Seok; Jung, Ui-Won; Lee, In-Seop

2013-01-01

47

Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption.  

PubMed

The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis. PMID:20876238

Azuma, Kotaro; Casey, Stephanie C; Ito, Masako; Urano, Tomohiko; Horie, Kuniko; Ouchi, Yasuyoshi; Kirchner, Séverine; Blumberg, Bruce; Inoue, Satoshi

2010-12-01

48

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

PubMed

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

Stein, Koen; Prondvai, Edina

2014-02-01

49

Lamellar Spacing in Cuboid Hydroxyapatite Scaffolds Regulates Bone Formation by Human Bone Marrow Stromal Cells  

PubMed Central

Background A major goal in bone engineering is the creation of large volume constructs (scaffolds and stem cells) that bear load. The scaffolds must satisfy two competing requirements—they need be sufficiently porous to allow nutrient flow to maintain cell viability, yet sufficiently dense to bear load. We studied the effect of scaffold macroporosity on bone formation and scaffold strength, for bone formed by human bone marrow stromal cells. Methods Rigid cubical hydroxyapatite/tricalcium phosphate scaffolds were produced by robo-casting. The ceramic line thickness was held constant, but the distance between adjacent lines was either 50, 100, 200, 500, or 1000??m. Cultured human bone marrow stromal cells were combined with the scaffolds in vitro; transplants were placed into the subcutis of immunodeficient mice. Transplants were harvested 9, 18, 23, 38, or 50 weeks later. Bone formation and scaffold strength were analyzed using histology and compression testing. Results Sixty transplants were evaluated. Cortical bone increased with transplant age, and was greatest among 500??m transplants. In contrast, maximum transplant strength was greatest among 200??m transplants. Conclusions Lamellar spacing within scaffolds regulates the extent of bone formation; 500??m yields the most new bone, whereas 200??m yields the strongest transplants. PMID:21294634

Afghani, Shahrzad; Franco, Jaime; Launey, Max; Marshall, Sally; Marshall, Grayson W.; Nissenson, Robert; Lee, Janice; Tomsia, Antoni P.; Saiz, Eduardo

2011-01-01

50

Early structure formation from cosmic string loops  

SciTech Connect

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??>10{sup ?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 [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, 212 College Avenue, Medford, MA 02155 (United States); Loeb, Abraham, E-mail: shlaer@cosmos.phy.tufts.edu, E-mail: vilenkin@cosmos.phy.tufts.edu, E-mail: aloeb@cfa.harvard.edu [Institute for Theory and Computation, Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA, 02138 (United States)

2012-05-01

51

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

PubMed Central

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

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

2014-01-01

52

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

SciTech Connect

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

Riis, B.J.; Christiansen, C.

1988-04-01

53

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

PubMed Central

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

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

2014-01-01

54

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. PMID:22298955

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

2012-01-01

55

Value of Bone Marrow Imprint Smears in Early Diagnosis Of Bone Marrow Pathologies  

PubMed Central

Background: Examination of bone marrow plays a pivotal role in the practice of haematology. It can be evaluated by three ways–bone marrow aspiration (BMA), bone marrow touch imprints (BMI) and bone marrow biopsy (BMBx). Aim and Objective: To study the efficacy and reliability of BMI smears in comparison to BMA smears, in making a diagnosis of diseases involving bone marrow. Setting and Designs: This study was carried out in the Department of Pathology, Institute of Medical Sciences, Varanasi over a period of 26 months. Materials and Methods: A total number of 182 cases, with their BMA, BMI and BMBx samples (from each and every case), were evaluated and their findings even compared. Statistical Analysis: All the observations were evaluated using simple and basic statistical tool, i.e. percentage. Results: The cellularity or cell density on BMI correlated with the cellularity of BMBx in 78.6% cases, which was higher than the value observed with BMA smears (71.4%). The spreading quality was better and cytological details were better appreciated in BMI as compared to BMA. Also, the presence of lymphoglandular bodies and particles on BMI were additive diagnostic clues. All of those findings were reflected in the higher diagnostic accuracy of BMI than BMA. Conclusion: BMI should be a standard practice and be considered as an early and reliable diagnostic tool for evaluating bone marrow pathologies PMID:25584225

Das, Subhajit; Bundhun, Soobashchan

2014-01-01

56

Bone formation induced by BMP-2 in human osteosarcoma cells  

PubMed Central

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 ALDH br 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 1×10 4 ALDH lo cells treated with 30 ? g 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

57

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

2013-10-01

58

The stimulation of bone formation in vitro by therapeutic ultrasound  

Microsoft Academic Search

A controlled study was performed to evaluate the effects of different ultrasound (US) intensities on 5-day-old mouse calvaria bone in tissue culture. A special technique to apply the US was developed, and the following parameters were measured: collagen and noncollagenous protein (NCP) synthesis (bone formation), and temperature change. It was found that ultrasound at 0.1 W\\/cm 2 (SATA), pulsed 1:4,

Peter Reher; El-Noor I. Elbeshir; Wilson Harvey; Sajeda Meghji; Malcolm Harris

1997-01-01

59

Soluble silica inhibits osteoclast formation and bone resorption in vitro.  

PubMed

Several studies have suggested that silicon (Si) may be essential for the normal development of connective tissue and the skeleton. Positive effects of Si from the diet as well as from Si-containing biomaterials, such as bioactive glass 45S5 (BG), have been demonstrated. Studies have reported that Si stimulates osteoblast proliferation and differentiation. However, the effects of Si on osteoclasts have not been directly addressed. The purpose of the present in vitro study was to clarify if Si has regulatory effects on osteoclast formation and bone resorption. The effects of BG, BG dissolution extracts and Si containing cell culture medium were investigated in a mouse calvarial bone resorption assay and osteoclast formation assays (mouse bone marrow cultures and RAW264.7 cell cultures). We conclude from our results that Si causes significant inhibition of osteoclast phenotypic gene expressions, osteoclast formation and bone resorption in vitro. In conclusion, the present study suggests that Si has a dual nature in bone metabolism with stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. This suggested property of Si might be interesting to further explore in future biomaterials for treatments of bone defects in patients. PMID:24016843

Mladenovi?, Živko; Johansson, Anders; Willman, Britta; Shahabi, Kaveh; Björn, Erik; Ransjö, Maria

2014-01-01

60

Fossil traces of the bone-eating worm Osedax in early Oligocene whale bones  

PubMed Central

Osedax is a recently discovered group of siboglinid annelids that consume bones on the seafloor and whose evolutionary origins have been linked with Cretaceous marine reptiles or to the post-Cretaceous rise of whales. Here we present whale bones from early Oligocene bathyal sediments exposed in Washington State, which show traces similar to those made by Osedax today. The geologic age of these trace fossils (?30 million years) coincides with the first major radiation of whales, consistent with the hypothesis of an evolutionary link between Osedax and its main food source, although older fossils should certainly be studied. Osedax has been destroying bones for most of the evolutionary history of whales and the possible significance of this “Osedax effect” in relation to the quality and quantity of their fossils is only now recognized. PMID:20424110

Kiel, Steffen; Goedert, James L.; Kahl, Wolf-Achim; Rouse, Greg W.

2010-01-01

61

Porphyromonas gingivalis infection increases osteoclastic bone resorption and osteoblastic bone formation in a periodontitis mouse model  

PubMed Central

Background Porphyromonas gingivalis has been shown to invade osteoblasts and inhibit their differentiation and mineralization in vitro. However, it is unclear if P. gingivalis can invade osteoblasts in vivo and how this would affect alveolar osteoblast/osteoclast dynamics. This study aims to answer these questions using a periodontitis mouse model under repetitive P. gingivalis inoculations. Methods For 3-month-old BALB/cByJ female mice, 109 CFU of P. gingivalis were inoculated onto the gingival margin of maxillary molars 4 times at 2-day intervals. After 2 weeks, another 4 inoculations at 2-day intervals were applied. Calcein was injected 7 and 2 days before sacrificing animals to label the newly formed bone. Four weeks after final inoculation, mice were sacrificed and maxilla collected. Immunohistochemistry, micro-CT, and bone histomorphometry were performed on the specimens. Sham infection with only vehicle was the control. Results P. gingivalis was found to invade gingival epithelia, periodontal ligament fibroblasts, and alveolar osteoblasts. Micro-CT showed alveolar bone resorption and significant reduction of bone mineral density and content in the infected mice compared to the controls. Bone histomorphometry showed a decrease in osteoblasts, an increase in osteoclasts and bone resorption, and a surprisingly increased osteoblastic bone formation in the infected mice compared to the controls. Conclusions P. gingivalis invades alveolar osteoblasts in the periodontitis mouse model and cause alveolar bone loss. Although P. gingivalis appears to suppress osteoblast pool and enhance osteoclastic bone resorption, the bone formation capacity is temporarily elevated in the infected mice, possibly via some anti-microbial compensational mechanisms. PMID:25027664

2014-01-01

62

Re-evaluating the induction of bone formation in primates.  

PubMed

The molecular cloning of the osteogenic proteins of the transforming growth factor-? (TGF-?) supergene family and the results of numerous pre-clinical studies in several mammalian species including non-human primates, have prematurely convinced molecular biologists, tissue engineers and skeletal reconstructionists alike to believe that single recombinant human bone morphogenetic/osteogenic proteins (hBMPs/OPs) would result in tissue induction when translated in clinical contexts. This theoretical potential has not been translated to acceptable clinical results. Clinical trials in craniofacial and orthopedic applications such as mandibular reconstruction and sinus-lift operations have indicated that supra physiological doses of a single recombinant human protein are needed to induce unacceptable tissue regeneration whilst incurring significant costs without achieving equivalence to autogenous bone grafts. The acid test for clinically relevant bone tissue engineering should now become the concept of clinically significant osteoinduction, whereby the regenerated bone is readily identifiable on radiographic examination by virtue of its opacity and trabecular architecture. The need for alternatives to the hBMPs/OPs is now felt more acutely following reported complications and performance failure associated with the clinical use of hBMP-2 and hOP-1 (BMP-7). Because of the often substandard regeneration of clinical defects implanted with hBMPs/OPs, we now need to finally deal with the provocative question: are the hBMPs/OPs the only initiators of the induction of bone formation in pre-clinical and clinical contexts? The rapid induction of bone formation by the hTGF-?? isoform in heteropic intramuscular sites of the Chacma baboon Papio ursinus together with TGF-??, TGF-??, BMP-2, BMP-3, OP-1, RUNX-2 and Osteocalcin up-regulation and expression, hyper cellular osteoblastic activity, osteoid synthesis, angiogenesis and capillary sprouting are the molecular and morphological foundation for the induction of bone formation in clinical contexts. The induction of bone as initiated by hTGF-?3 when implanted in the rectus abdominis muscle of P. ursinus is via the BMPs/OPs pathway with hTGF-?? controlling the induction of bone formation by regulating the expression of BMPs/OPs via Noggin expression, eliciting the induction of bone formation by up-regulating endogenous BMPs/OPs and it is blocked by hNoggin, providing insights into performance failure of hBMPs/OPs in clinical contexts. Physiological expression of BMPs/OPs genes upon implantation of hTGF-?? may escape the antagonist expression of Noggin and other inhibitors, whereas direct application of hBMPs/OPs, representing a later by-product step of the bone induction cascade as set by the TGF-?? master gene in primates, sets into motion Noggin' antagonist action, as shown by the limited effectiveness of hBMPs/OPs in clinical contexts. The unprecedented induction of bone formation by 250 ?g hTGF-?? when combined with coral-derived macroporous constructs is the novel molecular and morphological frontier for the induction of bone formation in man. The induction of bone by hTGF-?? has been thus translated in clinical contexts to treat a large mandibular defect in a pediatric patient; 30 months after implantation of 250 ?g hTGF-?? per gram of human demineralized bone matrix, radiographic analyses show the reconstruction of the avulsed large mandibular segment including the induction of the avulsed coronoid process. PMID:25155544

Ripamonti, Ugo; Duarte, Raquel; Ferretti, Carlo

2014-11-01

63

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. PMID:21732484

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

64

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

65

Non-Linear Pattern Formation in Bone Growth and Architecture  

PubMed Central

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

Salmon, Phil

2014-01-01

66

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

2011-12-16

67

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

PubMed Central

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

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

2013-01-01

68

Active multilayered capsules for in vivo bone formation  

PubMed Central

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled. PMID:20160118

Facca, S.; Cortez, C.; Mendoza-Palomares, C.; Messadeq, N.; Dierich, A.; Johnston, A. P. R.; Mainard, D.; Voegel, J.-C.; Caruso, F.; Benkirane-Jessel, N.

2010-01-01

69

MicroRNA control of bone formation and homeostasis  

PubMed Central

MicroRNAs (miRNAs) repress cellular protein levels to provide a sophisticated parameter of gene regulation that coordinates a broad spectrum of biological processes. Bone organogenesis is a complex process involving the differentiation and crosstalk of multiple cell types for formation and remodeling of the skeleton. Inhibition of mRNA translation by miRNAs has emerged as an important regulator of developmental osteogenic signaling pathways, osteoblast growth and differentiation, osteoclast-mediated bone resorption activity and bone homeostasis in the adult skeleton. miRNAs control multiple layers of gene regulation for bone development and postnatal functions, from the initial response of stem/progenitor cells to the structural and metabolic activity of the mature tissue. This Review brings into focus an emerging concept of bone-regulating miRNAs, the evidence for which has been gathered largely from in vivo mouse models and in vitro studies in human and mouse skeletal cell populations. Characterization of miRNAs that operate through tissue-specific transcription factors in osteoblast and osteoclast lineage cells, as well as intricate feedforward and reverse loops, has provided novel insights into the supervision of signaling pathways and regulatory networks controlling normal bone formation and turnover. The current knowledge of miRNAs characteristic of human pathologic disorders of the skeleton is presented with a future goal towards translational studies. PMID:22290358

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

2013-01-01

70

Effect of zinc supplementation on bone formation in hemodialysis patients with normal or low turnover bone.  

PubMed

Abstract Zinc (Zn) is an essential trace element, which has been shown to stimulate osteoblastic bone formation and to inhibit osteoclastic bone resorption in vitro. In thalassemia, major patients Zn supplementation was reported to increase whole-body bone mineral content and areal bone mineral density. Therefore, we investigated the effect of Zn supplementation on bone formation in hemodialysis (HD) patients. Nine male patients with age of 66 (35-78) years indicated by median (range), HD vintage of 57 (4-97) months and serum intact parathyroid hormone (PTH) of 113 (6-310) pg/mL were supplemented with polaprezinc containing 34?mg Zn/day for 18 months. Doses of vitamin D were not changed during supplementation. Blood was collected at baseline, 3, 6, 12 and 18 months. Serum Zn increased significantly from 58 (52-65)??g/dL to 71 (57-93) ?g/dL at three months and remained unchanged until 18 months. No changes were observed in serum intact PTH during supplementation. Although we found no changes in serum bone alkaline phosphatase (BAP) during Zn supplementation analyzed by Friedman test and Scheffe post hoc test, a significant trend of increase in serum BAP was verified by Jonckheere-Terpstra test (p?=?0.0409). On the contrary, there was no trend in serum TRACP5b by Jonckheere-Terpstra test. Therefore, we suggested the effect of Zn supplementation on promoting bone formation, not affected by the status of PTH and vitamin D, in HD patients with normal or low turnover bone. PMID:25207792

Shiota, Jun; Tagawa, Hitoshi; Izumi, Naoki; Higashikawa, Shingo; Kasahara, Hitoshi

2015-02-01

71

Bone formation in rabbit cancellous bone explant culture model is enhanced by mechanical load  

PubMed Central

Background When studying and designing an artificial bone in vitro with similar features and functionality of natural bone by tissue engineering technology, the culturing environment, especially the mechanical environment is supposed to be an important factor, because a suitable mechanical environment in vitro may improve the adaptability of the planted-in tissue engineering bone in the body. Unfortunately, up to now, the relationship between mechanical stimuli and natural bone growth has not yet been precisely determined, and it is so imperative for a prior study on effect of mechanical loading on growth of the natural bone cultured in vitro. Methods Under sterile conditions, explant models of rabbit cancellous bone with 3?mm in thickness and 8?mm in diameter were prepared and cultured in a dynamic loading and circulating perfusion bioreactor system. By Micro-CT scanning, a 3D model for finite element (FEM) analysis was achieved. According to the results of FEM analysis and physiological load bearing capacity of the natural bone, these models were firstly subjected to mechanical load with 1Hz frequency causing average apparent strain of 1000 ??, 2000 ??, 3000 ?? and 4000 ?? respectively for 30?min every day, activities of alkaline phosphatase (AKP) were detected on the 5th and the 14th loading day and on the 14th and the 21st day, mechanical properties, tissue mineral density (TMD) of the bone explant models were investigated and Von-kossa staining and fluorescence double labeling assays were conducted to evaluate whether there were fresh osteoid in the bone explant models. In addition, Western blot, Elisa and Real-time PCR were employed to analyze expression of Collagen-I (COL-1), bone morphogenetic protein-2 (BMP-2) and osteoprotegerin (OPG) protein and RNA. Results The explant models of rabbit cancellous bone prepared under sterile conditions grew well in the bioreactor system. With the increasing culturing time and load levels, bone explant models in groups with 1000 ?? and 2000 ?? average apparent strain experienced improving mechanical properties and TMD (P<0.05), and results of Von-kossa staining and fluorescence double labeling also showed apparent fresh osteoid formation. Under the same loading conditions, a up-regulations in protein and RNA of COL-1, BMP-2 and OPG were detected, especially, relative genes notably expressed after 21?days. Conclusion Our study demonstrated that mechanical load could improve function and activity of osteoblasts in explant models of cancellous bone. Through regulations of COL-1, OPG and BMP-2 secreted by osteoblasts, the mechanical load could improve the tissue structural density and stiffness due to formation of fresh osteoid. PMID:23597232

2013-01-01

72

Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.  

PubMed

Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ?60??m/day (0.8?mg/day), which was considerably higher than normal bone growth rates (several ?m/day, 0.1?mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone. PMID:24460696

Fernández, Tulio; Olave, Gilberto; Valencia, Carlos H; Arce, Sandra; Quinn, Julian M W; Thouas, George A; Chen, Qi-Zhi

2014-07-01

73

Immunolocalization of markers for bone formation during guided bone regeneration in osteopenic rats.  

PubMed

Objective The aim of this paper was to evaluate the repair of onlay autogenous bone grafts covered or not covered by an expanded polytetrafluoroethylene (e-PTFE) membrane using immunohistochemistry in rats with induced estrogen deficiency. Material and Methods Eighty female rats were randomly divided into two groups: ovariectomized (OVX) and with a simulation of the surgical procedure (SHAM). Each of these groups was again divided into groups with either placement of an autogenous bone graft alone (BG) or an autogenous bone graft associated with an e-PTFE membrane (BGM). Animals were euthanized on days 0, 7, 21, 45, and 60. The specimens were subjected to immunohistochemistry for bone sialoprotein (BSP), osteonectin (ONC), and osteocalcin (OCC). Results All groups (OVX+BG, OVX+BMG, SHAM+BG, and SHAM+BMG) showed greater bone formation, observed between 7 and 21 days, when BSP and ONC staining were more intense. At the 45-day, the bone graft showed direct bonding to the recipient bed in all specimens. The ONC and OCC showed more expressed in granulation tissue, in the membrane groups, independently of estrogen deficiency. Conclusions The expression of bone forming markers was not negatively influenced by estrogen deficiency. However, the markers could be influenced by the presence of the e-PTFE membrane. PMID:25591022

Tera, Tábata de Mello; Nascimento, Rodrigo Dias; Prado, Renata Falchete do; Santamaria, Mauro Pedrine; Jardini, Maria Aparecida Neves

2014-12-01

74

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

75

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

Microsoft Academic Search

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

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

76

Measurement of early bone loss around an uncemented femoral stem  

PubMed Central

Background and purpose Dual-energy X-ray absorptiometry (DXA) is a precise method to study changes in bone mineral density (BMD), including the pattern of bone remodeling around an implant. Results from implant studies are usually presented as changes in BMD as a function of time. The baseline and reference value for such calculations is the first measurement after the operation. The baseline measurement has been performed at different time points in different studies. If there is rapid bone loss immediately after an operation, this will influence the reference value and hence the results. To evaluate DXA as a method, we studied the very early changes by doing 3 DXA measurements within the first 2 weeks after surgery. Patients and methods We included 23 hips in 23 patients who were operated with an uncemented total hip prosthesis (THP). Each Gruen region was measured with DXA at 1, 5, and 14 days, and 3 and 12 months after the operation. 16 of the patients completed all 5 follow-ups. Results There was no detectable change in BMD in the first 14 days after the operation. In all zones, the lowest BMD was measured after 3 months. Interpretation We conclude that DXA measurements done within 14 days after the operation can be used as reference measurements for later follow-up studies. PMID:21504344

2011-01-01

77

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

78

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

PubMed

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

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

2015-06-01

79

Surface microcracks signal osteoblasts to regulate alignment and bone formation.  

PubMed

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

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

2014-11-01

80

Fresh-frozen allografts combined with bovine bone mineral enhance bone formation in sinus augmentation.  

PubMed

We evaluated histologically, histomorphometrically, and tomographically the effects of the association of fresh-frozen bone allograft (FFB) with bovine bone mineral (BBM) in maxillary sinus floor augmentation. In total, 34 maxillary sinuses from 29 patients, with a mean age of 51.32 (±6.44) years, underwent sinus augmentation. Patients were divided into control and test groups (17 sinuses each). The controls were grafted with allograft bone, and the test group received a combination of FFB and BBM at a 2:1 ratio. After 6 months, bone samples were collected for histological and histomorphometric examinations. The implant survival rates were 93.02% (control group) and 100% (test group) at 6 months after functional loading. Median volumetric reductions of 28.32% (17.05-44.05) and 12.62% (5.65-16.87) were observed for the control and test groups, respectively. Statistically significant histomorphometric differences were found between the control and test groups regarding newly formed bone 12.54% (10.50-13.33) vs. 24.42% (17.62-35.92), p?bone 48.34% (39.03-54.42) vs. 61.32% (50.61-64.96), p?=?0.007, and connective tissue 51.66% (45.57-60.97) vs. 39.30% (35.03-49.37), p?=?0.007. The addition of BBM to allograft bone in maxillary sinus augmentation resulted in higher percentages of new bone formation and total bone, and permitted implant placement with a low rate of osseointegration failure at the 6-month follow-up. PMID:25245781

Sehn, Felipe Perraro; Dias, Rafael Rodrigues; de Santana Santos, Thiago; Silva, Erick Ricardo; Salata, Luiz Antonio; Chaushu, Gavriel; Xavier, Samuel Porfírio

2015-02-01

81

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...

82

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

83

Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach  

PubMed Central

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, ?-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation. PMID:22754313

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

84

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

85

Static and dynamic osteogenesis: two different types of bone formation.  

PubMed

The onset and development of intramembranous ossification centers in the cranial vault and around the shaft of long bones in five newborn rabbits and six chick embryos were studied by light (LM) and transmission electron microscopy (TEM). Two subsequent different types of bone formation were observed. We respectively named them static and dynamic osteogenesis, because the former is characterized by pluristratified cords of unexpectedly stationary osteoblasts, which differentiate at a fairly constant distance (28+/-0.4 microm) from the blood capillaries, and the latter by the well-known typical monostratified laminae of movable osteoblasts. No significant structural and ultrastructural differences were found between stationary and movable osteoblasts, all being polarized secretory cells joined by gap junctions. However, unlike in typical movable osteoblastic laminae, stationary osteoblasts inside the cords are irregularly arranged, variously polarized and transform into osteocytes, clustered within confluent lacunae, in the same place where they differentiate. Static osteogenesis is devoted to the building of the first trabecular bony framework having, with respect to the subsequent bone apposition by typical movable osteoblasts, the same supporting function as calcified trabeculae in endochondral ossification. In conclusion, it appears that while static osteogenesis increases the bone external size, dynamic osteogenesis is mainly involved in bone compaction, i.e., in filling primary haversian spaces with primary osteons. PMID:12478364

Ferretti, Marzia; Palumbo, Carla; Contri, Miranda; Marotti, Gastone

2002-12-01

86

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

2013-11-01

87

Multi-protein Delivery by Nanodiamonds Promotes Bone Formation  

PubMed Central

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.

2013-01-01

88

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. PMID:19240811

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

2009-01-01

89

Biologic properties of nano-hydroxyapatite: An in vivo study of calvarial defects, ectopic bone formation and bone implantation.  

PubMed

This study investigated the biologic properties of nano-hydroxyapatite (nHAp) using the rat calvarial defect, ectopic bone formation, and rabbit tibia implant installation models. Animals were divided into two groups: those implanted with nHAp, and negative controls (Collagen). Eight weeks after creating an 8 mm calvarial defect, bone regeneration was evaluated radiographically and histologically. To investigate ectopic bone formation, materials were injected into the right thigh muscle and were evaluated after 8 weeks. nHAp coated implant and conventional titanium implant were placed bilaterally in rabbit tibias. After 4 weeks, bone-implant contact (BIC), new bone area inside the thread, and removal torque were measured. In the calvarial defect model, radiographic and histologic analysis showed more bone formation in the nHAp Group; particularly, histologically assessed bone area (p=0.034) and microcomputed tomography assessed bone mineral density (p=0.034). In the ectopic bone formation model, calcification and expression of osteogenic biomarkers were seen in the nHAp-injected samples but in none of the controls. nHAp coated implant resulted in increased BIC, new bone area, and increased removal torque, with statistical significance for BIC (p=0.034). This study suggests that nHAp has potential as a coating material for dental implant surfaces and as a bone graft material. PMID:25585978

Pang, Kang-Mi; Lee, Jeong-Keun; Seo, Young-Kwon; Kim, Soung-Min; Kim, Myung-Jin; Lee, Jong-Ho

2015-01-01

90

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

PubMed Central

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

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

2012-01-01

91

Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein.  

PubMed

Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross-linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP-2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2-incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP-2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back of mice, the radioactivity remaining in the hydrogels was measured to estimate the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution form was cleared from the injected site within one day, completely disappearing within 3 days. Ectopic bone formation studies demonstrated that BMP-2-incorporating gelatin hydrogels exhibited a more potent ability for bone induction than solution injection of BMP-2. This finding indicates that enhanced retention of BMP-2 is promotes its ability to induce ectopic bone formation. PMID:9648026

Yamamoto, M; Tabata, Y; Ikada, Y

1998-01-01

92

Sequential Application of Steady and Pulsatile Medium Perfusion Enhanced the Formation of Engineered Bone  

PubMed Central

In native bone, cells experience fluctuating shear forces that are induced by pulsatile interstitial flow associated with habitual loading. We hypothesized that the formation of engineered bone can be augmented by replicating such physiologic stimuli to osteogenic cells cultured in porous scaffolds using bioreactors with medium perfusion. To test this hypothesis, we investigated the effect of fluid flow regime on in vitro bone-like tissue development by human adipose stem cells (hASC) cultivated on porous three-dimensional silk fibroin scaffolds. To this end, we varied the sequential relative durations of steady flow (SF) and pulsatile flow (PF) of culture medium applied over a period of 5 weeks, and evaluated their effect on early stages of bone formation. Porous silk fibroin scaffolds (400–600??m pore size) were seeded with hASC (30×106 cells/mL) and cultured in osteogenic medium under four distinct fluid flow regimes: (1) PF for 5 weeks; (2) SF for 1 week, PF for 4 weeks; (3) SF for 2 weeks, PF for 3 weeks; (4) SF for 5 weeks. The PF was applied in 12?h intervals, with the interstitial velocity fluctuating between 400 and 1200??m/s at a 0.5?Hz frequency for 2?h, followed by 10?h of SF. In all groups, SF was applied at 400??m/s. The best osteogenic outcomes were achieved for the sequence of 2 weeks of SF and 3 weeks of PF, as evidenced by gene expression (including the PGE2 mechanotransduction marker), construct compositions, histomorphologies, and biomechanical properties. We thus propose that osteogenesis in hASC and the subsequent early stage bone development involve a mechanism, which detects and responds to the level and duration of hydrodynamic shear forces. PMID:23259605

Correia, Cristina; Bhumiratana, Sarindr; Sousa, Rui A.; Reis, Rui L.

2013-01-01

93

Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation.  

PubMed

Osteoporosis is caused by excessive activity of bone-degrading osteoclasts over bone-forming osteoblast. Standard antiosteolytic treatments inhibit bone resorption by inducing osteoclast loss, with the adverse effect of hindering also bone formation. Formation of the osteoclast sealing zone requires Dock5, a guanine nucleotide exchange factor for the small GTPase Rac, and C21, a chemical inhibitor of Dock5, decreases bone resorption by cultured osteoclasts. Here we show that C21 directly inhibits the exchange activity of Dock5 and disrupts osteoclast podosome organization. Remarkably, C21 administration protects mice against bone degradation in models recapitulating major osteolytic diseases: menopause, rheumatoid arthritis and bone metastasis. Furthermore, C21 administration does not affect bone formation and is not toxic. Our results validate the pharmacological inhibition of Dock5 as a novel therapeutic route for fighting osteolytic diseases while preserving bone formation. PMID:25645278

Vives, Virginie; Cres, Gaëlle; Richard, Christian; Busson, Muriel; Ferrandez, Yann; Planson, Anne-Gaelle; Zeghouf, Mahel; Cherfils, Jacqueline; Malaval, Luc; Blangy, Anne

2015-01-01

94

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

Microsoft Academic Search

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

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

2006-01-01

95

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

PubMed Central

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

2012-01-01

96

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

PubMed

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

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

2014-12-01

97

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

PubMed Central

The purpose of this study was to demonstrate spatial control of osteoblast differentiation in vitro and bone formation in vivo using inkjet bioprinting technology and to create three-dimensional persistent bio-ink patterns of bone morphogenetic protein-2 (BMP-2) and its modifiers immobilized within microporous scaffolds. Semicircular patterns of BMP-2 were printed within circular DermaMatrix™ human allograft scaffold constructs. The contralateral halves of the constructs were unprinted or printed with BMP-2 modifiers, including the BMP-2 inhibitor, noggin. Printed bio-ink pattern retention was validated using fluorescent or 125I-labeled bio-inks. Mouse C2C12 progenitor cells cultured on patterned constructs differentiated in a dose-dependent fashion toward an osteoblastic fate in register to BMP-2 patterns. The fidelity of spatial restriction of osteoblastic differentiation at the boundary between neighboring BMP-2 and noggin patterns improved in comparison with patterns without noggin. Acellular DermaMatrix constructs similarly patterned with BMP-2 and noggin were then implanted into a mouse calvarial defect model. Patterns of bone formation in vivo were comparable with patterned responses of osteoblastic differentiation in vitro. These results demonstrate that three-dimensional biopatterning of a growth factor and growth factor modifier within a construct can direct cell differentiation in vitro and tissue formation in vivo in register to printed patterns. PMID:20028232

Miller, Eric D.; DeCesare, Gary E.; Usas, Arvydas; Lensie, Emily L.; Bykowski, Michael R.; Huard, Johnny; Weiss, Lee E.; Losee, Joseph E.; Campbell, Phil G.

2010-01-01

98

Biglycan modulates angiogenesis and bone formation during fracture healing.  

PubMed

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

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

2014-04-01

99

Identification of Mechanosensitive Genes during Embryonic Bone Formation  

PubMed Central

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 on particular mechanical forces in vivo. We propose a new means of selecting candidate mechanosensitive genes by comparing in vivo gene expression patterns with patterns of biophysical stimuli, computed using finite element analysis. In this study, finite element analyses of the avian embryonic limb were performed using anatomically realistic rudiment and muscle morphologies, and patterns of biophysical stimuli were compared with the expression patterns of four candidate mechanosensitive genes integral to bone development. The expression patterns of two genes, Collagen X (ColX) and Indian hedgehog (Ihh), were shown to colocalise with biophysical stimuli induced by embryonic muscle contractions, identifying them as potentially being involved in the mechanoregulation of bone formation. An altered mechanical environment was induced in the embryonic chick, where a neuromuscular blocking agent was administered in ovo to modify skeletal muscle contractions. Finite element analyses predicted dramatic changes in levels and patterns of biophysical stimuli, and a number of immobilised specimens exhibited differences in ColX and Ihh expression. The results obtained indicate that computationally derived patterns of biophysical stimuli can be used to inform a directed search for genes that may play a mechanoregulatory role in particular in vivo events or processes. Furthermore, the experimental data demonstrate that ColX and Ihh are involved in mechanoregulatory pathways and may be key mediators in translating information from the mechanical environment to the molecular regulation of bone formation in the embryo. PMID:19112485

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

2008-01-01

100

Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model  

Microsoft Academic Search

To understand the contribution of IL-6\\/IL-6R to subchondral bone and bone marrow abnormality in RA patients and the effects of tocilizumab on those abnormalities, we evaluated early change in a collagen-induced arthritis (CIA) monkey model with or without a single administration of tocilizumab. Six CIA cynomolgus monkeys received tocilizumab and 3 CIA monkeys received vehicle only. Their interphalangeal joints were

Atsuhiko Kato; Saori Matsuo; Hirotake Takai; Yasushi Uchiyama; Masahiko Mihara; Masami Suzuki

2008-01-01

101

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

102

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

PubMed Central

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

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

2013-01-01

103

Evaluation of bone formation guided by DNA/protamine complex with FGF-2 in an adult rat calvarial defect model.  

PubMed

DNA/protamine complex paste (D/P) and D/P complex paste with Fibroblast Growth Factor-2 (FGF-2) (D/P-FGF) were prepared to investigate their new bone formation abilities using an ?40-week-old rat calvarial defect model. It was found that D/P could release FGF-2 proportionally in an in vitro experiment with an enzyme-linked immunosorbent assay. It was also found that aging adversely affected self-bone healing of rats by comparison with the results in a previous study using 10-week-old rats. Microcomputed tomography and histopathological examinations showed that new bone formation abilities of D/P and D/P-FGF were superior to that of the control (sham operation). Control, D/P and D/P-FGF showed newly formed bone areas of 6.7, 58.3, and 67.0%, respectively, 3 months after the operation. Moreover, it was found that FGF-2 could support the osteoanagenesis ability of D/P. It was considered that FGF-2 could play an important role in new bone formation at early stages because it induced the genes such as collagen I, CBFA, OSX, and OPN, which are initiated first in the process of osteogenesis. Therefore, D/P-FGF will be a useful injectable biomaterial with biodegradable properties for the repair of bone defects in the elderly. PMID:24664968

Shinozaki, Yosuke; Toda, Masako; Ohno, Jun; Kawaguchi, Minoru; Kido, Hirofumi; Fukushima, Tadao

2014-11-01

104

Putative Function of TAP63? during Endochondral Bone Formation  

PubMed Central

P63, a member of the P53 tumor suppressor family, is known to play important functions in cancer and development. Interestingly, previous studies have shown that p63 null mice are absent or have truncated limbs, while mutations in human P63 cause several skeletal syndromes that also show limb and digit abnormalities, suggesting its essential role in long bone development. Indeed, we detected increased level of p63 transcript in hypertrophic MCT cells (an established cell model of chondrocyte maturation) than in proliferative MCT cells. To investigate the in vivo role of P63 upon endochondral bone formation, we have established transgenic mouse lines in which HA- and Flag-tagged TAP63? (the longest P63 isoform) is driven by the hypertrophic chondrocyte-specific Col10a1 regulatory elements. Skeletal staining of Col10a1-TAP63? transgenic mice at either embryonic day 17.5 (E17.5) or postnatal day 1 (P1) observed accelerated ossification in long bone, digit and tail bones compared to their wild-type littermates, suggesting a putative function of P63 during skeletal development. We also detected decreased level of Sox9 and Bcl-2 transcripts, while Alp and Ank are slightly upregulated in Col10a1-TAP63? transgenic mouse limbs. Further immunohistochemical analysis confirmed the decreased Sox9 expression in the proliferative and hypertrophic zone of these mice. Von Kossa staining suggests increased mineralization in hypertrophic zone of transgenic mice compared to littermate controls. Together, our results suggest a role of TAP63? upon skeletal development. TAP63a may promote endochondral ossification through interaction with genes relevant to matrix mineralization and chondrocyte maturation or apoptosis PMID:22244744

Li, Feifei; Lu, Yaojuan; Ding, Ming; Wu, Guojun; Sinha, Satrajit; Wang, Siying; Zheng, Qiping

2012-01-01

105

Bone loss or lost bone: rationale and recommendations for the diagnosis and treatment of early postmenopausal bone loss.  

PubMed

Recent reports suggest that bone loss begins during late perimenopause at a dramatic rate, even before estrogen levels plummet. During the ensuing 5 years, there is evidence of the beginnings of microarchitectural deterioration, which impacts bone strength and ultimately enhances its propensity to fracture. The diagnosis of osteoporosis based on T-scores alone, or through stratification for a high fracture risk by FRAX, excludes these women who are rapidly losing bone. Because all antiosteoporosis therapies, in particular bisphosphonates, reduce bone loss, we propose aggressive, likely short-term therapy with a goal to reduce bone loss, stabilize bone density, and prevent microarchitectural deterioration. PMID:19968915

Zaidi, Mone; Turner, Charles H; Canalis, Ernesto; Pacifici, Roberto; Sun, Li; Iqbal, Jameel; Guo, X Edward; Silverman, Stuart; Epstein, Solomon; Rosen, Clifford J

2009-12-01

106

The p38? MAPK Function in Osteoprecursors Is Required for Bone Formation and Bone Homeostasis in Adult Mice  

PubMed Central

Background p38 MAPK activity plays an important role in several steps of the osteoblast lineage progression through activation of osteoblast-specific transcription factors and it is also essential for the acquisition of the osteoblast phenotype in early development. Although reports indicate p38 signalling plays a role in early skeletal development, its specific contributions to adult bone remodelling are still to be clarified. Methodology/Principal Findings We evaluated osteoblast-specific deletion of p38? to determine its significance in early skeletogenesis, as well as for bone homeostasis in adult skeleton. Early p38? deletion resulted in defective intramembranous and endochondral ossification in both calvaria and long bones. Mutant mice showed reduction of trabecular bone volume in distal femurs, associated with low trabecular thickness. In addition, knockout mice also displayed decreased femoral cortical bone volume and thickness. Deletion of p38? did not affect osteoclast function. Yet it impaired osteoblastogenesis and osteoblast maturation and activity through decreased expression of osteoblast-specific transcription factors and their targets. Furthermore, the inducible Cre system allowed us to control the onset of p38? disruption after birth by removal of doxycycline. Deletion of p38? at three or eight weeks postnatally led to significantly lower trabecular and cortical bone volume after 6 or 12 months. Conclusions Our data demonstrates that, in addition to early skeletogenesis, p38? is essential for osteoblasts to maintain their function in mineralized adult bone, as bone anabolism should be sustained throughout life. Moreover, our data also emphasizes that clinical development of p38 inhibitors should take into account their potential bone effects. PMID:25007355

Rodríguez-Carballo, Edgardo; Gámez, Beatriz; Sedó-Cabezón, Lara; Sánchez-Feutrie, Manuela; Zorzano, Antonio; Manzanares-Céspedes, Cristina; Rosa, José Luis; Ventura, Francesc

2014-01-01

107

NF-?B RelB negatively regulates osteoblast differentiation and bone formation.  

PubMed

RelA-mediated NF-?B canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-?B RelB may also negatively regulate bone formation through noncanonical signaling, but they involved a complex knockout mouse model, and the molecular mechanisms involved were not investigated. Here, we report that RelB(-/-) mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB(-/-) bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runt-related transcription factor 2 (Runx2). In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB(-/-) bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair. PMID:24115294

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

2014-04-01

108

Ibuprofen Administered Pre- or Post- Simulated Resistance Exercise Training Does Not Diminsh Gains in Bone Formation or Bone Mass  

E-print Network

Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to suppress bone formation when administered before, but not if administered after, an acute bout of mechanical load in rats. The NSAID ibuprofen inhibits cyclooxygenase-2 enzyme...

Cunningham, David

2012-02-14

109

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. PMID:23300855

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

2012-01-01

110

Bone Formation in a Rat Tibial Defect Model Using Carboxymethyl Cellulose/BioC/Bone Morphogenic Protein-2 Hybrid Materials  

PubMed Central

The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP)?:?hydroxyapatite (Hap) = 70?:?30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8?mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5?mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1?mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5?mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1?mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5?mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1?mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects. PMID:24804202

Kim, Hak-Jun; Park, Kyeongsoon; Kim, Sung Eun; Song, Hae-Ryong

2014-01-01

111

Growth in early life predicts bone strength in late adulthood: The Hertfordshire Cohort Study  

Microsoft Academic Search

Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength.We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939

Helen Oliver; Karen A. Jameson; Avan Aihie Sayer; Cyrus Cooper; Elaine M. Dennison

2007-01-01

112

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

113

Personalized Unicompartmental Knee Implant Treats Early Stage Arthritis While Preserving Bone  

MedlinePLUS Videos and Cool Tools

Personalized Unicompartmental Knee Implant Treats Early Stage Arthritis while Preserving Bone (6:00pm CST) You must have Javascript enabled in your web browser. View Program Transcript Click Here to ...

114

The effect of bovine whey protein on ectopic bone formation in young growing rats  

Microsoft Academic Search

The beneficial effect of bovine whey protein (WP) on bone metabolism has been shown in adult human subjects and ovariectomised rats. However, its effect on bone formation in earlier life, particularly during periods of bone mineral accrual, has not been investigated. Twenty-one male rats (4 weeks old, Wistar strain) were randomised by weight into three groups of seven rats each

Owen Kelly; Siobhan Cusack; Kevin D. Cashman

2003-01-01

115

Controlled delivery of platelet-rich plasma-derived growth factors for bone formation  

E-print Network

. Orthopedic and maxillofacial bone defects are frequently reconstructed with either auto- logous or allogeneic has been reported to improve the aggregation and cohesiveness of partic- ulate-based bone substitutesControlled delivery of platelet-rich plasma-derived growth factors for bone formation Helen H. Lu,1

Lu, Helen H.

116

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. 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.

2013-01-01

117

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

PubMed Central

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

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

2015-01-01

118

Formation of a bone apatite-like layer on the surface of porous hydroxyapatite ceramics.  

PubMed

Phosphoric acid solution was used to react with commercial hydroxyapatite (HA) powders to demonstrate the possibility of converting HA to non-stoichiometric apatite and thus to treat porous HA ceramics, to form a thin bone-apatite like layer on the HA ceramic surface. Such a carbonate-containing non-stoichiometric apatite "bioceramic" would be more efficient in bone bonding or bone formation, due to its analogy to natural bone apatite. PMID:7986949

Yubao, L; Klein, C P; Zhang, X; de Groot, K

1994-08-01

119

Epigenetic regulation of Tbx18 gene expression during endochondral bone formation.  

PubMed

Endochondral bone formation is tightly regulated by the spatial and sequential expression of a series of transcription factors. To disclose the roles of TBX18, a member of the T-box transcription factor family, during endochondral bone formation, its spatial and temporal expression patterns were characterized in the limb skeletal region of the developing mouse together with those of established osteochondrogenic markers Sox9, Col2a1, and Runx2. TBX18 expression first appeared in condensed mesenchymal cells (chondro-progenitors) in embryonic-day-10.5 (E10.5) limb bud and was co-localized with Sox9 expression, whereas at E11.5 and E12.5, it became undetectable in mesenchymal cells committed to the chondrocyte lineage. From E13.5 to E18.5, TBX18 expression reappeared in chondrocytes, correlating strongly with Col2a1 expression; furthermore, low level TBX18 expression was found in the Runx2-positive perichondral osteoblastic cell lineage. At the postnatal stage, TBX18 expression was observed in epiphyseal chondrocytes and osteocytes within the lacunae of mature trabecular bone. On the assumption that such characteristic Tbx18 gene expression is epigenetically regulated during mouse limb development, we examined the methylation status of the CpG-island in the mouse Tbx18 gene by methylation-specific polymerase chain reaction. Hypermethylation of the Tbx18 gene promoter became evident at an early embryonic stage in TBX18-negative cells and then disappeared at a late embryonic stage in TBX18-positive cells. Therefore, the temporal suppression of Tbx18 gene expression by the hypermethylation of its promoter seems to trigger the differentiation of mesenchymal cells into hypertrophic chondrocytes in the early stages of endochondral ossification. PMID:25380565

Haraguchi, Ryuma; Kitazawa, Riko; Kitazawa, Sohei

2014-11-01

120

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

PubMed

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

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

2012-08-01

121

Methodology developed for the simultaneous measurement of bone formation and bone resorption in rats based on the pharmacokinetics of fluoride.  

PubMed

This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date. PMID:24445963

Lupo, Maela; Brance, Maria Lorena; Fina, Brenda Lorena; Brun, Lucas Ricardo; Rigalli, Alfredo

2015-01-01

122

Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss  

PubMed Central

Targeted disruption of the histidine decarboxylase gene (HDC?/?), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC?/? mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC?/? mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1?-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-?B ligand concentrations, and suppressed parathyroid hormone concentrations in HDC?/? mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption. PMID:12716972

Fitzpatrick, L. A.; Buzas, E.; Gagne, T. J.; Nagy, A.; Horvath, C.; Ferencz, V.; Mester, A.; Kari, B.; Ruan, M.; Falus, A.; Barsony, J.

2003-01-01

123

Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome  

Microsoft Academic Search

It is well established that chronic excess of glucocorticoids has negative effects on bone and collagen turnover, and that secondary osteoporosis is a known clinical complication of endogenous Cushing's syndrome (CS). The aim of the present study was to evaluate bone dimension and bone mineral content in relation to biochemical markers of bone and collagen turnover, in a consecutive series

Kristin Godang; Thor Ueland; Jens Bollerslev

1999-01-01

124

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

PubMed Central

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 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 sacrificed 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 between groups (p<0,05). Histological examination revealed an intimate contact between the newly formed bone and the resorbing bone screws. Conclusion: Bovine bone screws provide environment for new bone formation and thus may provide an alternative therapy for enhancing bone formation vertically, including for regenerative procedures as well as prior to 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

2013-01-01

125

Aromatase inhibitors-induced bone loss in early breast cancer.  

PubMed

Women with breast cancer have an increased prevalence and incidence of fractures. This increased risk of fracture has become most evident following the use of aromatase inhibitors (AIs) as standard adjuvant therapy. AI-induced bone loss occurs at more than twice the rate of physiologic postmenopausal bone loss. Moreover, peripheral quantitative computed tomography data indicate that effects of AIs on bone strength and on cortical bone have been substantially underestimated by dual-energy X-ray absorptiometry. All AIs have been associated with an increased fracture risk. The incidence of fractures is at least 33-43% higher in AI-treated patients than in tamoxifen-treated patients, and this increase in fracture risk is maintained at least for the duration of AI therapy. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and denosumab to preserve and even increase bone mineral density (BMD) during adjuvant AIs. Most data have been obtained with zoledronic acid administered twice a year, which effectively maintains or increases BMD in women receiving AIs. In addition, zoledronic acid has been shown to delay disease recurrence and maybe prolong survival in women with hormone-responsive tumors, thereby providing an adjuvant antitumor benefit besides preserving BMD. It is likely that a combined fracture risk assessment will more accurately identify women with breast cancer who require bone protective therapy. The FRAX tool probably underestimates the net increase in fracture risk due to AI therapy. Recent guidelines for the prevention of AI-induced bone loss have adequately considered the presence of several established clinical risk factors for fractures, in addition to BMD, when selecting patients to be treated with inhibitors of bone resorption. PMID:24936287

Body, Jean-Jacques

2012-01-01

126

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

NASA Technical Reports Server (NTRS)

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

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

1998-01-01

127

Effect of the combination of enamel matrix derivatives and deproteinized bovine bone materials on bone formation in rabbits’ calvarial defects  

PubMed Central

Background: Various types of materials are used in bone regeneration procedures. The aim of this study was to investigate the use of the enamel matrix derivative (EMD), deproteinized bovine bone mineral (Bio-Oss), and a combination of Bio-Oss plus EMD in the treatment of bone defects created in the rabbits’ calvaria. Materials and Methods: Twenty New Zealand white rabbits were included in this experimental randomized single blind study. Four equal cranial bone defects (3 × 6 × 0.5 mm3) were created in frontal and parietal bone and randomly grafted with Bio-Oss (Group 1), EMD (Group 2), EMD + Bio-Oss (Group 3) and one of them was left unfilled to serve as a control group (Group 4). After 2, 4, 8, and 12 weeks the defects were evaluated by using histological and histomorphometric analysis. Data were analyzed by the Bonferroni test using SPSS 13 statistical software. P value <0.05 considered as statistically significant level. Results: Bone formation in the EMD + Bio-Oss group after 2 weeks was diminished when statistically compared to the other groups (P < 0.05). Bone augmentation after 4 weeks from the lowest to the highest were found in groups 1, 3, 2, and 4, respectively, and these differences were statistically significant (P < 0.05). Using EMD with Bio-Oss increased bone formation in the non-critical defects in the rabbit calvaria during 8 and 12 weeks (P < 0.05). Conclusions: Boosting of EMD plus Bio-Oss seems to have synergic effect on bone regeneration in bone defects. PMID:23162582

Shahriari, Shahriar; Houshmand, Behzad; Razavian, Hamid; Khazaei, Saber; Abbas, Fatemeh Mashhadi

2012-01-01

128

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

SciTech Connect

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

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

1987-06-01

129

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

PubMed Central

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

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

2008-01-01

130

Endochondral bone formation in gelatin methacrylamide hydrogel with embedded cartilage-derived matrix particles.  

PubMed

The natural process of endochondral bone formation in the growing skeletal system is increasingly inspiring the field of bone tissue engineering. However, in order to create relevant-size bone grafts, a cell carrier is required that ensures a high diffusion rate and facilitates matrix formation, balanced by its degradation. Therefore, we set out to engineer endochondral bone in gelatin methacrylamide (GelMA) hydrogels with embedded multipotent stromal cells (MSCs) and cartilage-derived matrix (CDM) particles. CDM particles were found to stimulate the formation of a cartilage template by MSCs in the GelMA hydrogel in vitro. In a subcutaneous rat model, this template was subsequently remodeled into mineralized bone tissue, including bone-marrow cavities. The GelMA was almost fully degraded during this process. There was no significant difference in the degree of calcification in GelMA with or without CDM particles: 42.5 ± 2.5% vs. 39.5 ± 8.3% (mean ± standard deviation), respectively. Interestingly, in an osteochondral setting, the presence of chondrocytes in one half of the constructs fully impeded bone formation in the other half by MSCs. This work offers a new avenue for the engineering of relevant-size bone grafts, by the formation of endochondral bone within a degradable hydrogel. PMID:25453948

Visser, Jetze; Gawlitta, Debby; Benders, Kim E M; Toma, Selynda M H; Pouran, Behdad; van Weeren, P René; Dhert, Wouter J A; Malda, Jos

2015-01-01

131

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...

132

Scaphoid Osteosynthesis: Early Experience with the Herbert Bone Screw  

Microsoft Academic Search

The results of our first fourteen patients with fractured scaphoids treated with the Herbert bone screw have been disappointing. Six have failed to unite. The operation is technically demanding and there is a high incidence of malpositioning of the screw which correlates with failure to achieve union. This is predictable from initial radiographs and peroperative radiology is advised. The osteosynthesis

D. J. PRING; E. B. HARTLEY; D. J. WILLIAMS

1987-01-01

133

Paget's disease of bone in early adult life  

PubMed Central

Methods: A retrospective two centre study of 314 patients with Paget's disease of bone from two university hospitals. The disease was diagnosed by radiological, serum alkaline phosphatase (AP) levels, or clinical features, and bone scintigraphy in most patients. Demographic data, reason for diagnosis, bones affected, disease extent using Coutris' index, complications during progression, and disease activity using Renier's index were assessed. Patients over and under 40 were compared. Results: 18/314 (5.7%) patients were diagnosed before the age of 40; median (SD) age was 35.4 (5.5) (range 18–40) and AP 555.6 (566.3) IU/l (range 70–1949). Coutris' extension index was 12.8 (10.5) and Renier's activity index 35.9 (31.9). Younger patients had more affected bones (p<0.05) than those aged >40, higher level of extension (p<0.05), higher AP value (p = 0.05), and greater incidence of thoracolumbar spine disease. Disease activity did not differ significantly between the groups. Conclusions: Paget's disease diagnosed before the age of 40 is more extensive but not more active, with higher AP values than in those diagnosed after age 40. PMID:15647439

Holgado, S; Rotes, D; Guma, M; Monfort, J; Olive, A; Carbonell, J; Tena, X

2005-01-01

134

Early planet formation as a trigger for further planet formation  

Microsoft Academic Search

Recent discoveries of extrasolar giant planets at small orbital radii, or having significant orbital eccentricities, suggest that the planets interacted with the disks of dust and gas from which they and the central stars formed. Here we show that if a gas-giant planet reaches a mass of 4-5 jovian masses sufficiently early, when the protoplanetary disk is still massive, an

Philip J. Armitage; Brad M. S. Hansen

1999-01-01

135

The effect of diabetes mellitus on rat mandibular bone formation and microarchitecture.  

PubMed

The aim of this study was to assess the effect of type 1 diabetes mellitus (DM) on the structure of mandibular bone and on the changes of alveolar/jaw bone formation. Experimental DM was induced in 3-wk-old male Wistar rats by a single dose of 60 mg/kg body weight of streptozotocin. All rats were injected with calcein on days 21 and 28. The rats were killed when 8 wk of age. Bone structure was analyzed by bone histomorphometry, microcomputed tomography (micro-CT), and histological section. Histomorphometric analysis showed that the mineral apposition and the bone formation rates in most of the mandibular regions were significantly decreased in the DM group compared with the control group. Micro-CT analysis showed significant deterioration of the bone quality in rats with DM. For a histometric measure of bone resorption, the number of osteoclasts along the distal surface of the alveolar wall was counted. The number of osteoclasts was significantly lower in the rats with DM than in the controls. These findings suggest that uncontrolled DM decreases mandibular bone formation, reduces the rate of bone turnover in the alveolar wall surrounding the root, and affects the quality of bone structure resulting in retardation of its skeletal development. PMID:20662909

Abbassy, Mona A; Watari, Ippei; Soma, Kunimichi

2010-08-01

136

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

137

Gene Expression Analyses of Subchondral Bone in Early Experimental Osteoarthritis by Microarray  

PubMed Central

Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subchondral bone in the early stages of experimental osteoarthritis in a rat model. We identified 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks post-surgery. Further analyses of the dysregulated genes indicated that the events underlying subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some of the identified dysregulated genes that were identified have suspected roles in bone development or remodeling; these genes include Alp, Igf1, Tgf ?1, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were confirmed by real-time PCR, and the results indicated that our microarray data accurately reflected gene expression patterns characteristic of early OA. To validate the results of our microarray analysis at the protein level, immunohistochemistry staining was used to investigate the expression of Mmp3 and Aspn protein in tissue sections. These analyses indicate that Mmp3 protein expression completely matched the results of both the microarray and real-time PCR analyses; however, Aspn protein expression was not observed to differ at any time. In summary, our study demonstrated a simple method of separation of subchondral bone sample from the knee joint of rat, which can effectively avoid bone RNA degradation. These findings also revealed the gene expression profiles of subchondral bone in the rat OA model at multiple time points post-surgery and identified important DE genes with known or suspected roles in bone development or remodeling. These genes may be novel diagnostic markers or therapeutic targets for OA. PMID:22384228

Chen, YuXian; Shen, Jun; Lu, HuaDing; Zeng, Chun; Ren, JianHua; Zeng, Hua; Li, ZhiFu; Chen, ShaoMing; Cai, DaoZhang; Zhao, Qing

2012-01-01

138

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. PMID:23908115

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

2013-01-01

139

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

PubMed Central

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

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

2014-01-01

140

Bone morphogenetic proteins, eye patterning, and retinocollicular map formation in the mouse  

PubMed Central

Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC). RGC axon behaviors during retinotopic map formation in wild type mice are compared with those in several strains of mice with engineered defects of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the optic tract that reflects the dorsoventral position of the parent RGCs in the eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC axons as they exit the optic chiasm. This sorting is not dependent on EphB. When BMP signaling in the developing eye is genetically modified, RGC order in the optic tract and targeting in the LGN and SC are correspondingly disrupted. These experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC axon behavior in the ascending optic tract and retinotopic map formation in the LGN and SC through mechanisms that are in part distinct from EphB signaling in the LGN and SC. PMID:18614674

Plas, Daniel T.; Dhande, Onkar; Lopez, Joshua E.; Murali, Deepa; Thaller, Christina; Henkemeyer, Mark; Furuta, Yasuhide; Overbeek, Paul; Crair, Michael C.

2009-01-01

141

Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone  

PubMed Central

Background & objectives: Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. Methods: HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. Results: The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. Interpretation & conclusions: The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone. PMID:23852290

Sulaiman, Shamsul Bin; Keong, Tan Kok; Cheng, Chen Hui; Saim, Aminuddin Bin; Idrus, Ruszymah Bt. Hj

2013-01-01

142

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

PubMed

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

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

2006-05-01

143

FLUORIDE EFFECTS ON BONE FORMATION AND MINERALIZATION ARE INFLUENCED BY GENETICS  

PubMed Central

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

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

2008-01-01

144

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

PubMed Central

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

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

2012-01-01

145

Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix.  

PubMed

The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1-deficient mice showed reduced mineralization of both membranous and endochondral bones. MicroCT (?CT) analysis of the calvarial bones (i.e., frontal, parietal and interparietal bones collectively) indicated that bone volume in Fbln1 nulls at neonatal stage P0 were reduced by 22% (p=0.015). Similarly, Fbln1 null frontal bones showed a 16% (p=0.035) decrease in bone volume, with a reduction in the interfrontal bone, and a discontinuity in the leading edge of the frontal bone. To determine whether Fbln1 played a role in osteoblast differentiation during bone formation, qPCR was used to measure the effects of Fbln1 deficiency on the expression of Osterix (Osx), a transcription factor essential for osteoblast differentiation. This analysis demonstrated that Osx mRNA was significantly reduced in Fbln1-deficient calvarial bones at developmental stages E16.5 (p=0.049) and E17.5 (p=0.022). Furthermore, the ability of Bmp-2 to induce Osx expression was significantly diminished in Fbln1-deficient mouse embryo fibroblasts. Together, these findings indicate that Fbln1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of Bmp signaling. PMID:25201465

Cooley, Marion A; Harikrishnan, Keerthi; Oppel, James A; Miler, Sloan F; Barth, Jeremy L; Haycraft, Courtney J; Reddy, Sakamuri V; Scott Argraves, W

2014-12-01

146

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

147

The effect of semelil (angipars®) on bone resorption and bone formation markers in type 2 diabetic patients  

PubMed Central

Background and purpose of the study Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of Angipars® for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need to evaluate the effect of this new drug on different organs including bone resorption and bone formation markers. Methods In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects were randomly divided into intervention and control groups. Subjects of intervention group received 100?mg of Angipars® twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3?months. Result 31 patients in study group and 30 patients in control group finished the study. The mean age of the study population and the mean disease duration was respectively 51.8?±?6.2 and 7.5?±?4.7?years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-?). Only urine creatinine level significantly changed between two groups after 3?month of treatment (p-value: 0.029) Conclusion In conclusion, the findings of this study indicate that Semelil (Angipars®) had no beneficial or harmful effects on bone. It might be other effects of this new component on bone turnover process which need more studies and more time to be discovered. PMID:23351359

2012-01-01

148

Joint Loading Modality: Its Application to Bone Formation and Fracture Healing  

PubMed Central

Sports related injuries such as impact and stress fractures often require a rehabilitation program to stimulate bone formation and accelerate fracture healing. This review introduces a recently developed joint loading modality and evaluates its potential applications to bone formation and fracture healing in post-injury rehabilitation. Bone is a dynamic tissue whose structure is constantly altered in response to its mechanical environments. Indeed, many loading modalities can influence the bone remodeling process. The joint loading modality is, however, able to enhance anabolic responses and accelerate wound healing without inducing significant in situ strain at the site of bone formation or fracture healing. This review highlights the unique features of this loading modality and discusses its potential underlying mechanisms as well as possible clinical applications. PMID:18048437

Zhang, Ping; Malacinski, George M.; Yokota, Hiroki

2010-01-01

149

Local Mechanical Stimuli Regulate Bone Formation and Resorption in Mice at the Tissue Level  

PubMed Central

Bone is able to react to changing mechanical demands by adapting its internal microstructure through bone forming and resorbing cells. This process is called bone modeling and remodeling. It is evident that changes in mechanical demands at the organ level must be interpreted at the tissue level where bone (re)modeling takes place. Although assumed for a long time, the relationship between the locations of bone formation and resorption and the local mechanical environment is still under debate. The lack of suitable imaging modalities for measuring bone formation and resorption in vivo has made it difficult to assess the mechanoregulation of bone three-dimensionally by experiment. Using in vivo micro-computed tomography and high resolution finite element analysis in living mice, we show that bone formation most likely occurs at sites of high local mechanical strain (p<0.0001) and resorption at sites of low local mechanical strain (p<0.0001). Furthermore, the probability of bone resorption decreases exponentially with increasing mechanical stimulus (R2?=?0.99) whereas the probability of bone formation follows an exponential growth function to a maximum value (R2?=?0.99). Moreover, resorption is more strictly controlled than formation in loaded animals, and ovariectomy increases the amount of non-targeted resorption. Our experimental assessment of mechanoregulation at the tissue level does not show any evidence of a lazy zone and suggests that around 80% of all (re)modeling can be linked to the mechanical micro-environment. These findings disclose how mechanical stimuli at the tissue level contribute to the regulation of bone adaptation at the organ level. PMID:23637993

Schulte, Friederike A.; Ruffoni, Davide; Lambers, Floor M.; Christen, David; Webster, Duncan J.; Kuhn, Gisela; Müller, Ralph

2013-01-01

150

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

PubMed Central

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

Nguyen, Daniel; Alliston, Tamara

2013-01-01

151

Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles.  

PubMed

Calcium phosphate ceramics are widely used in bone reconstructive surgery because of their osteconductive properties. However, these materials generally lack osteoinductive properties required to support bone healing in large defects. In this article, we study the osteoinductive potential of calcium phosphate ceramic particles implanted for 6 months into the dorsal muscles of eight adult female sheep. Microporous biphasic calcium phosphate (MBCP) granules of 1-2 mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) had macropores of 450 microm, micropores of 0.43 microm, and a specific surface area of 1.8 m(2)/g. After 6 months in the back muscles of sheep, the explants composed of MBCP granules were hard and encapsulated by normal muscle tissue. Ectopic bone formation with Haversian structures was observed in close contact with the MBCP granules in histological sections. Back-scattered electron microscopy and micro-computed tomography indicated that approximately 10% of well-mineralized bone with mature osteocytes had formed between or upon the granules. The ectopic bone showed trabeculae bridging the MBCP granules. Both the number and thickness of the trabeculae formed between the MBCP particles were comparable to those measured in spongious bone. The overall results therefore confirmed the presence of mature bone after intramuscular implantation of MBCP granules. The different hypotheses explaining ectopic bone formation induced by MBCP granules are discussed. Synthetic bone substitutes with osteoinductive properties could be used in bone reconstructive surgery. PMID:15869915

Le Nihouannen, Damien; Daculsi, Guy; Saffarzadeh, Afchine; Gauthier, Olivier; Delplace, Séverine; Pilet, Paul; Layrolle, Pierre

2005-06-01

152

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...

153

Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model.  

PubMed

To understand the contribution of IL-6/IL-6R to subchondral bone and bone marrow abnormality in RA patients and the effects of tocilizumab on those abnormalities, we evaluated early change in a collagen-induced arthritis (CIA) monkey model with or without a single administration of tocilizumab. Six CIA cynomolgus monkeys received tocilizumab and 3 CIA monkeys received vehicle only. Their interphalangeal joints were analyzed using HE, silver impregnation (SI), or immunohistochemistry (RANKL) staining. The number of osteoclasts increased in the arthritis control but was suppressed in the tocilizumab-treated animals. Osteoblast/stromal cells of the arthritis control monkeys were of monolayer, while in the tocilizumab-treated monkeys, the cells were multi-layer or differentiated osteoblasts, and the meshwork of the reticulum fibers showed recovery in the SI. Hematopoietic marrow was replaced by interstitial fluid and reticulum fibers were eliminated in the arthritic model but showed recovery in the tocilizumab-treated animals. RANKL showed overproduction with arthritis and suppressed with tocilizumab treatment. The evidence indicates that IL-6/IL-6R is involved in subchondral bone and bone marrow change in RA patients. Tocilizumab treatment recovered changes in the CIA monkeys as a result of the co-differentiation between the osteoclasts and the osteoblast/stramal cells, at least partially through the suppression of RANKL overproduction. PMID:18511040

Kato, Atsuhiko; Matsuo, Saori; Takai, Hirotake; Uchiyama, Yasushi; Mihara, Masahiko; Suzuki, Masami

2008-06-01

154

Regulation of bone resorption and formation by purines and pyrimidines  

E-print Network

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

Burnstock, Geoffrey

155

Normal Tempo of Bone Formation in Turner Syndrome despite Signs of Accelerated Bone Resorption  

Microsoft Academic Search

Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n = 49), assessed by dual-energy X-ray absorptiometry, bone markers and hormones. TS patients

Line Cleemann; Kirsten Holm; Hanne Kobbernagel; Sven O. Skouby; Bent Kristensen; Heidi Smedegaard; Anna-Maria Andersson; Arieh Cohen; Claus H. Gravholt

2011-01-01

156

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

157

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

2013-02-01

158

Up-regulation of glycolytic metabolism is required for HIF1?-driven bone formation  

PubMed Central

The bone marrow environment is among the most hypoxic in the body, but how hypoxia affects bone formation is not known. Because low oxygen tension stabilizes hypoxia-inducible factor alpha (HIF?) proteins, we have investigated the effect of expressing a stabilized form of HIF1? in osteoblast precursors. Brief stabilization of HIF1? in SP7-positive cells in postnatal mice dramatically stimulated cancellous bone formation via marked expansion of the osteoblast population. Remarkably, concomitant deletion of vascular endothelial growth factor A (VEGFA) in the mouse did not diminish bone accrual caused by HIF1? stabilization. Thus, HIF1?-driven bone formation is independent of VEGFA up-regulation and increased angiogenesis. On the other hand, HIF1? stabilization stimulated glycolysis in bone through up-regulation of key glycolytic enzymes including pyruvate dehydrogenase kinase 1 (PDK1). Pharmacological inhibition of PDK1 completely reversed HIF1?-driven bone formation in vivo. Thus, HIF1? stimulates osteoblast formation through direct activation of glycolysis, and alterations in cellular metabolism may be a broadly applicable mechanism for regulating cell differentiation. PMID:24912186

Regan, Jenna N.; Lim, Joohyun; Shi, Yu; Joeng, Kyu Sang; Arbeit, Jeffrey M.; Shohet, Ralph V.; Long, Fanxin

2014-01-01

159

Arthritis Induces Early Bone High Turnover, Structural Degradation and Mechanical Weakness  

PubMed Central

Background We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Methods Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. Results AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. Conclusions We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness. PMID:25617902

Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

2015-01-01

160

Platelets guide the formation of early metastatic niches  

PubMed Central

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

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

2014-01-01

161

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

PubMed Central

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

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

2013-01-01

162

Effect of hormone replacement therapy on bone quality in early postmenopausal women.  

PubMed

HRT is an effective prophylaxis against postmenopausal bone loss. Infrared imaging of paired iliac crest biopsies obtained at baseline and after 2 years of HRT therapy demonstrate an effect on the mineral crystallinity and collagen cross-links that may affect bone quality. Several studies have demonstrated that hormonal replacement therapy (HRT) is an effective prophylaxis against postmenopausal bone loss, although the underlying mechanisms are still debated. Infrared spectroscopy has been used previously for analyzing bone mineral crystallinity and three-dimensional structures of collagen and other proteins. In the present study, the technique of Fourier transform infrared microscopic imaging (FTIRI) was used to investigate the effect of estrogen on bone quality (arbitrarily defined as mineral/matrix ratio, mineral crystallinity/maturity, and relative ratio of collagen cross-links [pyridinoline/ deH-DHLNL]) at the ultrastructural level, in mineralized, thin tissue sections from double (before and after administration of HRT regimen; cyclic estrogen and progestogen [norethisterone acetate]) iliac crest biopsy specimens from 10 healthy, early postmenopausal women who were not on any medication with known influence on calcium metabolism. FTIRI allows the analysis of undemineralized thin tissue sections (each image analyzes a 400 x 400 microm2 area with a spatial resolution of approximately 6.3 mm). For each bone quality variable considered, the after-treatment data exhibited an increase in the mean value, signifying definite changes in bone properties at the molecular level after HRT treatment. Furthermore, these findings are consistent with suppressed osteoclastic activity. PMID:12817747

Paschalis, E P; Boskey, A L; Kassem, M; Eriksen, E F

2003-06-01

163

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

164

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

ERIC Educational Resources Information Center

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

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

2002-01-01

165

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

PubMed

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

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

2014-10-01

166

Early Union of Grafted Bone in Ankylosing Spondylitis: Comparative Study with Degenerative Spinal Disease  

PubMed Central

Background Patients with ankylosing spondylitis (AS) achieve early bone union compared to those with other spinal diseases. This study compared the time to bone union after surgery between AS patients and degenerative spinal disease patients. Methods Patients with degenerative spinal diseases (control group) and AS (experimental group) underwent pedicle subtraction osteotomy followed by posterolateral fusion, and decompression and posterolateral fusion, respectively. There were 10 patients in the experimental group. The control group included 26 patients who were less than 50 years of age and underwent two-level autogenous grafting after decompression and spinal fusion. Autogenous grafts and a range of bone substitutes were used in the experimental group, whereas only autogenous grafts were used in the control group. Bone union was determined on the radiographs and 3-dimensional CT scan images. The level of union was assessed using the Lenke's and Christensen's classification systems. Results In the experimental group, the mean age was 41.3 years (range, 30 to 67 years), the mean follow-up period was 21.7 months (range, 12 to 43 months), and bone union was confirmed at an average of 3.5 months (range, 3 to 5 months) after surgery. In the control group, the mean age was 43.1 years (range, 35 to 50 years), the mean follow-up period was 21.8 months (range, 12 to 74 months), and bone union was observed at an average of 5.6 months (range, 4 to 12 months) after surgery. The difference in the time to bone union between the two groups was significant (p = 0.023). Conclusions The union of grafted bone was obtained earlier in patients with AS than in those with degenerative spinal diseases. Therefore, future studies should examine the factors affecting the early union in AS patients. PMID:21119936

Lee, Chang-Hun; Kim, Jae-Hun; Kim, Tae-Hwan

2010-01-01

167

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

PubMed Central

Background Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings We found that Per2Brdm1 mutant mice as well as mice lacking Cry2?/? displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2?/? displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2?/? mutants despite the simultaneous inactivation of Per2. Conclusions/Significance This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters. PMID:20634945

Seitz, Sebastian; Schinke, Thorsten; Schmutz, Isabelle; van der Horst, Gijsbertus; Amling, Michael; Albrecht, Urs

2010-01-01

168

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

NASA Technical Reports Server (NTRS)

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

Suda, Tatsuo

1993-01-01

169

Osthole Stimulates Osteoblast Differentiation and Bone Formation by Activation of ?-Catenin–BMP Signaling  

PubMed Central

Osteoporosis is defined as reduced bone mineral density with a high risk of fragile fracture. Current available treatment regimens include antiresorptive drugs such as estrogen receptor analogues and bisphosphates and anabolic agents such as parathyroid hormone (PTH). However, neither option is completely satisfactory because of adverse effects. It is thus highly desirable to identify novel anabolic agents to improve future osteoporosis treatment. Osthole, a coumarin-like derivative extracted from Chinese herbs, has been shown to stimulate osteoblast proliferation and differentiation, but its effect on bone formation in vivo and underlying mechanism remain unknown. In this study, we found that local injection of Osthole significantly increased new bone formation on the surface of mouse calvaria. Ovariectomy caused evident bone loss in rats, whereas Osthole largely prevented such loss, as shown by improved bone microarchitecture, histomorphometric parameters, and biomechanical properties. In vitro studies demonstrated that Osthole activated Wnt/?-catenin signaling, increased Bmp2 expression, and stimulated osteoblast differentiation. Targeted deletion of the ?-catenin and Bmp2 genes abolished the stimulatory effect of Osthole on osteoblast differentiation. Since deletion of the Bmp2 gene did not affect Osthole-induced ?-catenin expression and the deletion of the ?-catenin gene inhibited Osthole-regulated Bmp2 expression in osteoblasts, we propose that Osthole acts through ?-catenin–BMP signaling to promote osteoblast differentiation. Our findings demonstrate that Osthole could be a potential anabolic agent to stimulate bone formation and prevent estrogen deficiency–induced bone loss. © 2010 American Society for Bone and Mineral Research. PMID:20200936

Tang, De-Zhi; Hou, Wei; Zhou, Quan; Zhang, Minjie; Holz, Jonathan; Sheu, Tzong-Jen; Li, Tian-Fang; Cheng, Shao-Dan; Shi, Qi; Harris, Stephen E; Chen, Di; Wang, Yong-Jun

2010-01-01

170

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

SciTech Connect

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

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O'Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

2013-10-15

171

Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.  

PubMed

Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. PMID:24975579

Esteve-Altava, Borja; Rasskin-Gutman, Diego

2014-09-01

172

Bone structure and strength are enhanced in rats programmed by early overfeeding.  

PubMed

Childhood obesity is growing in prevalence. Obesity and bone dysfunctions may be related disorders, and therefore our aim was to study the impact of the early overfeeding (EO) in offspring bone health since weaning up to adulthood. To induce EO during lactation, litter size was adjusted to 3 male rats per litter (SL). Litter containing 10 pups per mother was the control (NL). Bone tissue was evaluated by dual-energy X-ray absorptiometry, computed tomography, microcomputed tomography, biomechanical tests, and serum analyses. SL offspring presented higher body weight, fat mass, lean mass from 21 up to 180 days, hyperphagia, and higher visceral fat mass. Bone analysis showed that SL offspring presented higher total bone mineral density (BMD) only at 180 days, and higher total bone mineral content and higher bone area from 21 until 180 days. At 180 days, SL offspring presented higher femur BMD and fourth lumbar vertebra (LV4) BMD, higher femoral head radiodensity and LV4 vertebral body radiodensity, lower trabecular pattern factor and trabecular separation, however with higher trabecular number, higher maximal load, resilience, stiffness and break load, and lower break deformation. SL group had, at 180 days, higher osteocalcin and lower C-terminal cross-linked telopeptide of type I collagen (CTX I). We have shown that the excess of fat mass contributed to an increased bone mass, and hypothesized that this increase could be mediated by the hypothyroidism and previous higher thyroid hormone action and hyperleptinemia at weaning. Furthermore, the increased biomechanical loading due to increased body weight probably help us to understand the protective effects obesity exerts upon bone health. PMID:24627101

de Albuquerque Maia, L; Lisboa, P C; de Oliveira, E; da Conceição, E P S; Lima, I C B; Lopes, R T; Ruffoni, L D G; Nonaka, K O; de Moura, E G

2014-04-01

173

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

174

Analysis of bone formation after sinus augmentation using ?-tricalcium phosphate.  

PubMed

Implant placement in the edentulous maxilla often represents a clinical challenge due to insufficient bone height after crestal bone resorption and maxillary sinus pneumatization. Several graft materials have been evaluated for augmenting the maxillary sinus to compensate for the lost vertical dimension. Allografts are readily available without the risk of disease transmission and the need for a second site surgery. The aim of this case series was to systematically evaluate the development and maturation of augmented bone in the maxillary sinus using beta-tricalcium phosphate. In 21 to 40 weeks post-sinus elevation, bone biopsies were taken and implants placed simultaneously. All specimens were demineralized and subjected to staining procedures (ie, Hematoxylin and Eosin [H&E], Goldner's staining, and tartrate-resistant acid phosphatase [TRAP]). Total bone increased over time, whereas the amount of graft material diminished. A lack of inflammatory reaction was noticed with the use of this graft material. In addition, TRAP staining revealed the presence of osteoclasts surrounding the remaining particles. During a 12-month follow-up, no implant failure or complications were observed. PMID:22616219

Schulze-Späte, Ulrike; Dietrich, Thomas; Kayal, Rayyan A; Hasturk, Hatice; Dobeck, Justine; Skobe, Ziedonis; Dibart, Serge

2012-05-01

175

Contribution of defect on early stage of LIPSS formation.  

PubMed

We investigated an early stage of laser-induced periodic surface structure (LIPSS) formation to elucidate the contribution of defects on the formation. 4H-SiC crystals were irradiated by multiple pulses of femtosecond laser with different laser spot sizes. We observed the decrease in formation thresholds of high-spatial-frequency LIPSS (HSFL) and low-spatial-frequency LIPSS (LSFL) with the increased irradiated laser spot size. For smaller laser spot size, HSFL was only formed at the periphery of LSFL formation area, whereas for larger spot size, HSFL was randomly distributed within the laser spot. Our results are coincident with the hypothesis that the existence of defects in crystal contributes to the early stage on the formation of LIPSS, in which the electron excitation via one or two photon absorption in a defect site cause local nanoablation at a laser fluence under the intrinsic ablation threshold, followed by the formation of a nanovoid, which act as a scatterer, and interference of scattered wave and laser pulses lead to HSFL formation. PMID:25089418

Shimizu, Hisashi; Yada, Shuhei; Obara, Go; Terakawa, Mitsuhiro

2014-07-28

176

Automatic quantification of early transition points in biofilm formation  

NASA Astrophysics Data System (ADS)

Biofilms are multicellular, dynamic communities of interacting single-cell organisms, like bacteria. Biofilms are responsible for many infectious diseases as well as for significant damage in industrial settings, yet many aspects of biofilm formation are not well understood. Identifying and quantifying the interactions leading to biofilm formation will not only be important for understanding the basic science of these and other multicellular systems, but it will also be essential for designing targeted strategies to prevent or disrupt biofilms. In particular, it is not clear what physical interactions, and corresponding biological mechanisms, are responsible for the early steps in biofilm formation. Because of this, we are developing high-throughput software techniques to analyze micrograph movies of biofilm formation, from attachment to surfaces through the development of microcolonies. This work will focus on developing software tools to identify and quantify key steps in biofilm formation, first in non-chemotacting systems and later in chemotacting (and autotacting) systems.

Thatcher, Travis; Bienvenu, Samuel; Strain, Shinji; Gordon, Vernita

2010-10-01

177

Prednisone-induced osteopenia in beagles: variable effects mediated by differential suppression of bone formation.  

PubMed

To examine the mechanism of glucocorticoid-induced osteopenia and the basis for variable bone loss after glucocorticoid administration, we gave prednisone (1.3 mg.kg-1.day-1) to normal male dogs (n = 15) for 29 wk to attempt induction of osteopenia. Compared with age-matched control dogs (n = 14), prednisone treatment rapidly decreased spinal bone density by 4.3%, as assessed by quantitative digital radiography, and reduced trabecular bone volume by 14.6%, as measured by quantitative histomorphology of iliac crest bone specimens. Bone loss was attenuated in prednisone-treated dogs after prolonged treatment (greater than 12 wk). Prednisone treatment resulted in diminished bone formation rates (15 +/- 3.4 vs. 47 +/- 4.5 microns/yr) and activation frequency (0.4 +/- 0.1 vs. 1.3 +/- 0.2/day). These findings indicate that suppression of osteoblastic function and recruitment is the primary histological abnormality mediating glucocorticoid-induced osteopenia in beagles. In contrast, prednisone administration had no effect on bone resorption or serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D, which suggests that these factors are not essential for prednisone-induced bone loss. Moreover, 33% of beagles were totally resistant to glucocorticoid-induced osteopenia. Such heterogeneity of bone loss was associated with variable suppressive effects of prednisone on osteoblastic function, as evidenced by greater bone formation rates and activation frequency in prednisone-resistant animals. Collectively, these observations suggest that glucocorticoid-induced bone loss results from a dynamic interplay between steroid-mediated suppression of osteoblastic function and recruitment and undefined compensatory factors that ameliorate the effects of glucocorticoids on osteoblastic precursors. PMID:1636691

Quarles, L D

1992-07-01

178

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

179

Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.  

PubMed

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

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

2014-01-01

180

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

NASA Astrophysics Data System (ADS)

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

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

2014-04-01

181

Microencapsulated rBMMSCs/calcium phosphate cement for bone formation in vivo.  

PubMed

As an injectable scaffold material for bone tissue engineering, calcium phosphate cement (CPC) has good biocompatibility, self-setting, and osteoconduction properties. Alginate-microencapsulated seed cells can pick up the degradation speed and bioactivity of CPC. The aim of this study was to explore the osteogenic ability of a composite of microencapsulated rabbit bone marrow mesenchymal stem cells (rBMMSCs) with ?-tricalcium phosphate/calcium phosphate cement (?-TCP/CPC) in vivo. Cavity defects were created in both femoral condylar regions of New Zealand White rabbits. ?-TCP/CPC (control group) and alginate microencapsulated rBMMSCs/?-TCP/CPC composite (composite group) were implanted separately into the bone defects of both femurs. Bone substitute degradation and new bone formation were evaluated by CBCT, and the defects were examined histologically 8, 16, and 24 weeks after implantation. In addition, fluorescent carbocyanine CM-Dil was used to track the rBMMSCs in vivo after implantation. The results showed that far more new bone and bone marrow grew into the bone defects in the composite group. Few CM-Dil labeled positive cells were observed postoperatively. However more native cells were detected in the graft areas of the composite group than those of the control group. The study indicates that a composite of microencapsulated seed cells/?-TCP/CPC might be considered as a promising injectable material for the generation of new bone tissue. PMID:24211970

Wang, Juan; Qiao, Pengyan; Dong, Limin; Li, Fangfang; Xu, Tao; Xie, Qiufei

2014-01-01

182

Enhanced control of in vivo bone formation with surface functionalized alginate microbeads incorporating heparin and human bone morphogenetic protein-2.  

PubMed

In this study, we tested the hypothesis that a surface functionalization delivery platform incorporating heparin onto strontium alginate microbeads surfaces would convert this "naive carriers" into "mini-reservoirs" for localized in vivo delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) that will induce functional bone regeneration. In vitro evaluation confirmed that (1) heparin incorporation could immobilize and prolong rhBMP-2 release for approximately 3 weeks; (2) a significant decrease (p<0.01) in rhBMP-2 burst release is attainable depending on initial protein load; and (3) rhBMP-2 released from surface functionalized microbeads retained bioactivity and stimulated higher alkaline phosphatase activity in cultured C(2)C(12) cells when compared with daily administration of fresh bolus rhBMP-2. Subsequently, surface functionalized microbeads were used for in vivo delivery of rhBMP-2 at local sites of posterolateral spinal fusion surgery in rats. The microbeads were loaded into the pores of medical-grade polyepsilone caprolactone-tricalcium phosphate scaffolds before implantation. Results revealed robust bone formation and a biomechanically solid fusion after 6 weeks. When compared with a control group consisting of an equivalent amount of rhBMP-2 that was directly adsorbed onto bare-surfaced microbeads with no heparin, a 5.3-fold increase in bone volume fraction and a 2.6-fold increase in bending stiffness (flexion/extension) were observed. When compared with collagen sponge carriers of rhBMP-2, a 1.5-fold and a 1.3-fold increase in bone volume fraction and bending stiffness were observed, respectively. More importantly, 3D micro-computed tomography images enabled the visualization of a well-contained newly formed bone at ipsilateral implant sites with surface functionalized rhBMP-2 delivery. This was absent with collagen sponge carriers where newly formed bone tissue was poorly contained and crossed over the posterior midline to contralateral implants. These findings are important because of complications with current rhBMP-2 delivery method, including excessive, uncontrolled bone formation. PMID:22894570

Abbah, Sunny Akogwu; Liu, Jing; Goh, James Cho Hong; Wong, Hee-Kit

2013-02-01

183

Was core formation violent enough to homogenize the early mantle?  

NASA Technical Reports Server (NTRS)

The dynamics of iron, its thermal state and its phase in the accreting Earth probably played a major role in the Earth's early thermal evolution. Plausible impact thermal histories make it possible that pure iron was molten in the accreting Earth after it was about 10% grown. Hence, iron eutectic alloys (FeS, FeO) certainly were. Additionally, the initial temperature of the core is an important constraint on the secular cooling of the early Earth and on the strength of the early geodynamo. Whether iron is solid or molten would influence geochemical equilibria in the upper and lower mantle; the mode of core formation, by spherical or near-spherical blobs, stalk-like instabilities, or something more catastrophic would influence the partitioning of siderophiles between silicate and iron phases. Early descent of iron (during accretion) favors partitioning according to low-pressure phase equilibria, whereas late descent favors higher pressure. The later core formation occurs, the greater the heat pulse, due to the strong dependence of gravitational potential energy on planetary radius. The heat may homogenize the mantle if core formation is global; otherwise, heterogeneity of iron differentiation may leave some of the pre-archean mantle unaffected. The larger the chunks of proto-core (and hence smaller surface/volume ratios) the greater the heterogeneity.

Cooperman, S. A.; Kaula, W. M.

1985-01-01

184

Hydroxyapatite grafting promotes new bone formation and osseointegration of smooth titanium implants.  

PubMed

Titanium is the ideal metal for intra-osseous dental implants. It permits the natural formation of an oxide layer on its surface and thereby it prevents the release of potentially toxic molecules. New formation of bone around implants, partially placed into the bone marrow cavity, is a gradual process that runs from the endosteum to the surface of the implant. Deposition of hydroxyapatite crystals on collagen type I fibrils is initiated by acidic proteins and leads to bone mineralization. This study analyzed the effects of hydroxyapatite upon peri-implant bone formation after insertion of smooth titanium implants. Screw-shaped smooth titanium implants of 3.75 mm thickness and 8.5 mm length were inserted into the metaphysis of rabbit tibia, either together with bovine hydroxyapatite into the right tibia or in controls without hydroxyapatite into the left tibia. Polyfluorochrome tracers (alizarin complex, calcein, tetracycline) were injected subcutaneously at different time intervals after implantation to evaluate the time frame of bone new formation over a period of 8 weeks. All samples were processed for histology and analyzed by fluorescence and polarizing microscopy. Our results showed a higher quantity of mature type I collagen fibers around implants and an acceleration of bone formation in the presence of hydroxyapatite. Mainly immature organic matrix was formed at the surface of implants in controls. The presence of hydroxyapatite seems to promote the maturation of collagen fibers surrounding the titanium implants and to support osteoconduction. Moreover, new formation of bone was faster in all samples where implants were inserted together with hydroxyapatite. PMID:16551011

Allegrini, Sergio; Rumpel, Elisabeth; Kauschke, Ellen; Fanghänel, Jochen; König, Bruno

2006-03-01

185

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

SciTech Connect

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

Montgomery, S.L. [Petroleum Consultant, Seattle, WA (United States)

1997-08-01

186

Growth in early life predicts bone strength in late adulthood: the Hertfordshire Cohort Study.  

PubMed

Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength. We studied 313 men and 318 women born in Hertfordshire between 1931 and 1939 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500). Birthweight and conditional weight at 1 year were strongly related to radial and tibial length in both sexes (p<0.001) and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use, and menopausal status in women. Among men, BMI was strongly positively associated with radial (r=0.46, p=0.001) and tibial (r=0.24, p=0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p=0.0002; tibia: p=0.08) and trabecular BMD (radius: p=0.08; tibia: p=0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p=0.0002; tibia: p=0.001) and trabecular (radius: p=0.008; tibia: p=0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p=0.006; fracture load X: p=0.005; fracture load Y: p=0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p=0.0001), cortical (p<0.005) and trabecular (p=0.0002) BMD, poorer forearm bone strength [polar SSI (p=0.006), fracture load X and Y (p=0.02)], and lower tibial total (p<0.001), cortical (p=0.008), and trabecular (p=0.0001) BMD. We have shown that growth in early life is associated with bone size and strength in a UK population aged 65-73 years. Lifestyle factors were associated with volumetric bone density in this population. PMID:17599849

Oliver, Helen; Jameson, Karen A; Sayer, Avan Aihie; Cooper, Cyrus; Dennison, Elaine M

2007-09-01

187

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

PubMed

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

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

2012-06-01

188

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

PubMed Central

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

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

2014-01-01

189

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

PubMed Central

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

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

2013-01-01

190

Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates cortical porosity with age.  

PubMed

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

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

2014-01-01

191

Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption  

E-print Network

fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium

Blumberg, Bruce

192

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

PubMed Central

Purpose. The association between serum lipids and bone mineral density (BMD) has been investigated previously but, up to now, these relationships have not yet been described in spinal cord injury (SCI). We tried to assess the correlation between serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) and BMD in male subjects with SCI. Methods. Dual-energy X-ray absorptiometry (DXA) was used to assess BMD in femoral neck, trochanter, intertrochanteric zone, and lumbar vertebras. Blood samples were taken to measure serums lipids and bone biomarkers including osteocalcin, cross-linked type I collagen (CTX), and bone alkaline phosphatase (BALP). Partial correlation analysis was used to evaluate the relationships between mentioned measurements after adjustment for weight and age. Results. We found a positive correlation between HDL and femoral neck BMD (P: 0.004, r = 0.33). HDL was negatively correlated with osteocalcin (P: 0.017, r = ?0.31) which was not in consistency with its relationship with BMD. TC and LDL were not related to CTX, BALP and BMD. Conclusion. This study does not support a strong association between serum lipids and BMD in subjects with SCI. Moreover it seems that positive association between HDL and BMD is not mediated through increased bone formation. PMID:25215260

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

2014-01-01

193

Bone formation at a rabbit skull defect by autologous bone marrow cells combined with gelatin microspheres containing TGF-beta1.  

PubMed

The objective of the present study is to investigate the addition effect of transforming growth factor (TGF)-beta1 on the bone formation at a rabbit skull defect induced by autologous bone marrow (BM). Following application of gelatin microspheres containing TGF-beta1, with or without BM cells to skull bone defects, bone formation at the defect was assessed by soft X-ray, dual energy X-ray absorptometry (DEXA), and histological examinations. After implantation for 6 weeks, gelatin microspheres containing 0.05 microg of TGF-beta1 plus 10(6) of BM cells induced bone formation at the 6 mm diameter bone defect. The defect was histologically closed by newly formed bone tissue, whilst both gelatin microspheres containing 0.05 microg of TGF-beta1, and 10(6) and 10(7) of BM cells were ineffective. A DEXA experiment revealed that combination of gelatin microspheres containing TGF-beta1 with BM cells enhanced the bone mineral density at the skull defect to a significantly greater extent than other agents. These findings indicate that a combination of gelatin microspheres containing TGF-beta1 enabled BM cells to enhance the osteoinductive ability, resulting in bone formation even at the cell number at which BM cells alone were ineffective. PMID:11211099

Tabata, Y; Hong, L; Miyamoto, S; Miyao, M; Hashimoto, N; Ikada, Y

2000-01-01

194

The mechanism of antibody formation in mouse bone marrow  

Microsoft Academic Search

The bone marrow (BM) is the major production site of B lymphocytes.\\u000aThe newly formed small B lymphocytes migrate, after a maturation period\\u000aof one or more days, to the peripheral lymphoid organs (spleen, lymph\\u000anodes, tonsils, etc.), where they can be activated by antigen (after\\u000awhich they can differentiate into antibody-forming cells) or die.\\u000aAccording to this view, most

G. Koch

1982-01-01

195

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

196

The paredon, Mexico, obsidian source and early formative exchange.  

PubMed

In 1975, archeological surface surveys of trade routes located again a pre-Hispanic obsidian source in central Mexico first reported in 1902. Initial trace element studies of the Paredón source through an analysis by neutron activation have been compared with similar studies of the obsidian found at Chalcatzingo 150 kilometers from the source. These comparisons indicate that obsidian from Paredón, rather than Otumba, was of primary importance during the Early Formative in central Mexico. PMID:17738531

Charlton, T H; Grove, D C; Hopke, P K

1978-09-01

197

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

198

Neonatal factors predicting childhood height in preterm infants: Evidence for a persisting effect of early metabolic bone disease?  

Microsoft Academic Search

Objectives: Preterm infants are known to remain small during childhood. We previously found that evidence of neonatal metabolic bone disease was associated with reduced length at 18 months. We aimed to further investigate factors predicting childhood height and to test the hypothesis that evidence of early metabolic bone disease is associated with reduced later height. Study design: A cohort of

Mary S. Fewtrell; Timothy J. Cole; Nicholas J. Bishop; Alan Lucas

2000-01-01

199

Apoptosis-associated uncoupling of bone formation and resorption in osteomyelitis  

PubMed Central

The mechanisms underlying the destruction of bone tissue in osteomyelitis are only now being elucidated. While some of the tissue damage associated with osteomyelitis likely results from the direct actions of bacteria and infiltrating leukocytes, perhaps exacerbated by bacterial manipulation of leukocyte survival pathways, infection-induced bone loss predominantly results from an uncoupling of the activities of osteoblasts and osteoclasts. Bacteria or their products can directly increase osteoclast formation and activity, and the inflammatory milieu at sites of infection can further promote bone resorption. In addition, osteoclast activity is critically regulated by osteoblasts that can respond to bacterial pathogens and foster both inflammation and osteoclastogenesis. Importantly, bone loss during osteomyelitis is also brought about by a decline in new bone deposition due to decreased bone matrix synthesis and by increased rates of osteoblast apoptosis. Extracellular bacterial components may be sufficient to reduce osteoblast viability, but the causative agents of osteomyelitis are also capable of inducing continuous apoptosis of these cells by activating intrinsic and extrinsic cell death pathways to further uncouple bone formation and resorption. Interestingly, bacterial internalization appears to be required for maximal osteoblast apoptosis, and cytosolic inflammasome activation may act in concert with autocrine/paracrine death receptor-ligand signaling to induce cell death. The manipulation of apoptotic pathways in infected bone cells could be an attractive new means to limit inflammatory damage in osteomyelitis. However, the mechanism that is the most important in bacterium-induced bone loss has not yet been identified. Furthermore, it remains to be determined whether the host would be best served by preventing osteoblast cell death or by promoting apoptosis in infected cells. PMID:24392356

Marriott, Ian

2013-01-01

200

Prednisolone prevents decreases in trabecular bone mass and strength by reducing bone resorption and bone formation defect in adjuvant-induced arthritic rats.  

PubMed

We examined the effects of prednisolone (PSL) administration in normal female Sprague Dawley rats and adjuvant-induced arthritic rats at the age of 6 weeks. Rats were intramuscularly injected with PSL twice a week at doses of 0 (control), 10, 30, 90, or 270 mg/kg body weight (b.w.). In the normal rats, serum osteocalcin level at 14 days and serum carboxyterminal pyridinoline cross-linked telopeptide of type 1 collagen (1CTP) level at 28 days in the 270 mg/kg dose group was lower than the respective value in control animals. The BMC and the trabecular bone formation rate (BFR/BS) of the lumbar body (L-4) in the 270 mg/kg dose group at 14 and 28 days were significantly lower than the values in the control rats. In the arthritic rats, however, serum osteocalcin levels in the PSL-treated groups did not differ compared with arthritic controls. The serum 1CTP levels in all of the PSL-treated groups were significantly reduced at 28 days. The age-dependent increases in the L4 BMC, BMD, and L-3 ultimate compressive load values were maintained. The BFR/BS values in the 90 mg/kg and 270 mg/kg dose groups were significantly higher than those in the arthritic control rats. The trabecular osteoclast number and surface values in all of the PSL-treated groups were significantly lower than the values in arthritic controls. These data demonstrate that PSL administration prevented reduction in bone mass and strength of the lumbar trabecular bone in adjuvant-induced arthritic rats by reducing the increase in bone resorption and the decrease in bone formation at both the local and systemic levels. PMID:9763147

Okazaki, Y; Tsurukami, H; Nishida, S; Okimoto, N; Aota, S; Takeda, S; Nakamura, T

1998-10-01

201

Assessment of bone formation by biochemical markers in metabolic bone disease: Separation between osteoblastic activity at the cell and tissue level  

Microsoft Academic Search

Summary In this study, serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S-BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as

P. Charles; C. Hasling; L. Risteli; J. Risteli; L. Mosekilde; E. F. Eriksen

1992-01-01

202

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

PubMed

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

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

2012-06-01

203

In vivo stimulation of bone formation by aluminum and oxygen plasma surface-modified magnesium implants.  

PubMed

A newly developed magnesium implant is used to stimulate bone formation in vivo. The magnesium implant after undergoing dual aluminum and oxygen plasma implantation is able to suppress rapid corrosion, leaching of magnesium ions, as well as hydrogen gas release from the biodegradable alloy in simulated body fluid (SBF). No released aluminum is detected from the SBF extract and enhanced corrosion resistance properties are confirmed by electrochemical tests. In vitro studies reveal enhanced growth of GFP mouse osteoblasts on the aluminum oxide coated sample, but not on the untreated sample. In addition to that a small amount (50 ppm) of magnesium ions can enhance osteogenic differentiation as reported previously, our present data show a low concentration of hydrogen can give rise to the same effect. To compare the bone volume change between the plasma-treated magnesium implant and untreated control, micro-computed tomography is performed and the plasma-treated implant is found to induce significant new bone formation adjacent to the implant from day 1 until the end of the animal study. On the contrary, bone loss is observed during the first week post-operation from the untreated magnesium sample. Owing to the protection offered by the Al2O3 layer, the plasma-treated implant degrades more slowly and the small amount of released magnesium ions stimulate new bone formation locally as revealed by histological analyses. Scanning electron microscopy discloses that the Al2O3 layer at the bone-implant interface is still present two months after implantation. In addition, no inflammation or tissue necrosis is observed from both treated and untreated implants. These promising results suggest that the plasma-treated magnesium implant can stimulate bone formation in vivo in a minimal invasive way and without causing post-operative complications. PMID:24060425

Wong, Hoi Man; Zhao, Ying; Tam, Vivian; Wu, Shuilin; Chu, Paul K; Zheng, Yufeng; To, Michael Kai Tsun; Leung, Frankie K L; Luk, Keith D K; Cheung, Kenneth M C; Yeung, Kelvin W K

2013-12-01

204

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

2013-12-01

205

The Importance of the Prenyl Group in the Activities of Osthole in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro  

PubMed Central

Osteoporosis treatment always aimed at keeping the balance of bone formation and bone resorption. Recently, prenyl group in natural products has been proposed as an active group to enhance the osteogenesis process. Osthole has both the prenyl group and bone-protective activities, but the relationship is still unknown. In this study we found that osthole exerted a potent ability to promote proliferation and osteogenic function of rat bone marrow stromal cells and osteoblasts, including improved cell viability, alkaline phosphatase activity, enhanced secretion of collagen-I, bone morphogenetic protein-2, osteocalcin and osteopontin, stimulated mRNA expression of insulin-like growth factor-1, runt-related transcription factor-2, osterix, OPG (osteoprotegerin), RANKL (receptor activator for nuclear factor-?B ligand), and the ratio of OPG/RANKL, as well as increasing the formation of mineralized nodules. However, 7-methoxycoumarin had no obvious effects. Osthole also inhibited osteoclastic bone resorption to a greater extent than 7-methoxycoumarin, as shown by a lower tartrate-resistant acid phosphatase activity and lower number and smaller area of resorption pits. Our findings demonstrate that osthole could be a potential agent to stimulate bone formation and inhibit bone resorption, and the prenyl group plays an important role in these bone-protective effects. PMID:25147567

Zhai, Yuan-Kun; Pan, Ya-Lei; Niu, Yin-Bo; Li, Chen-Rui; Wu, Xiang-Long; Fan, Wu-Tu; Lu, Ting-Li; Mei, Qi-Bing; Xian, Cory J.

2014-01-01

206

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.

Chassefiere, E.; Dartois, E.; Herri, J.; Tian, F.; Schmidt, F.; Mousis, O.; Lakhlifi, A.

2013-12-01

207

Nanoscale Confinement Controls the Crystallization of Calcium Phosphate: Relevance to Bone Formation  

PubMed Central

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

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

2015-01-01

208

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

PubMed Central

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

Takeshita, Sunao

2014-01-01

209

Titanium nanotubes activate genes related to bone formation in vitro  

PubMed Central

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

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

2012-01-01

210

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. PMID:7175438

1982-01-01

211

Structure formation in inhomogeneous Early Dark Energy models  

SciTech Connect

We study the impact of Early Dark Energy fluctuations in the linear and non-linear regimes of structure formation. In these models the energy density of dark energy is non-negligible at high redshifts and the fluctuations in the dark energy component can have the same order of magnitude of dark matter fluctuations. Since two basic approximations usually taken in the standard scenario of quintessence models, that both dark energy density during the matter dominated period and dark energy fluctuations on small scales are negligible, are not valid in such models, we first study approximate analytical solutions for dark matter and dark energy perturbations in the linear regime. This study is helpful to find consistent initial conditions for the system of equations and to analytically understand the effects of Early Dark Energy and its fluctuations, which are also verified numerically. In the linear regime we compute the matter growth and variation of the gravitational potential associated with the Integrated Sachs-Wolf effect, showing that these observables present important modifications due to Early Dark Energy fluctuations, though making them more similar to the ?CDM model. We also make use of the Spherical Collapse model to study the influence of Early Dark Energy fluctuations in the nonlinear regime of structure formation, especially on ?{sub c} parameter, and their contribution to the halo mass, which we show can be of the order of 10%. We finally compute how the number density of halos is modified in comparison to the ?CDM model and address the problem of how to correct the mass function in order to take into account the contribution of clustered dark energy. We conclude that the inhomogeneous Early Dark Energy models are more similar to the ?CDM model than its homogeneous counterparts.

Batista, R.C. [Escola de Ciências e Tecnologia, Universidade Federal do Rio Grande do Norte, Caixa Postal 1524, 59072-970, Natal, Rio Grande do Norte (Brazil); Pace, F., E-mail: rbatista@ect.ufrn.br, E-mail: francesco.pace@port.ac.uk [Institute of Cosmology and Gravitation, University of Portsmouth, Dennis Sciama Building, Portsmouth, PO1 3FX (United Kingdom)

2013-06-01

212

A case of refractory perforation at the floor of the mouth with ectopic bone formation.  

PubMed

Although most fistulae are not problematic, surgeons occasionally encounter recurrent and/or refractory fistulae in the field of oral and maxillofacial surgery. In this case report, the authors describe a case in which a patient experienced a recurrent and refractory fistula or perforation at his oral floor through the submandible, with heterotopic bone formation arising on both sides of the mylohyoid line. These heterotopic bones were connected to each other, forming a bone bridge at the center of the oral floor. A fistulectomy and wound closure with a tongue flap was successful. The perforation has not recurred after over four years of follow-up, and the bone bridge is still present. PMID:22586833

Ohba, Seigo; Sekine, Joji; Tobita, Takayoshi; Ikeda, Hideyoshi; Asahina, Izumi

2011-07-01

213

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

2013-02-01

214

S-nitroso albumin enhances bone formation in a rabbit calvaria model.  

PubMed

Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO-HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves (8 mm diameter, two per animal) were created by a trephine drill in the cortical bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone filled with a collagen sponge soaked with either 100 ?L S-NO-HSA (5%, 20%) or human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to histological and histomorphometric analysis. Bone formation and the volume of the residual collagen sponge were evaluated. S-NO-HSA treatment groups had a significantly higher volume of newly formed bone underneath the titanium hemispheres compared to the albumin control groups (5%: 15.5 ± 4.0% versus 10.6 ± 2.9%; P < 0.05; 20%: 14.0 ± 4.6% versus 6.0 ± 3.8%; P < 0.01). The volume of residual collagen sponge was also significantly lower in the S-NO-HSA groups compared to the control groups (5%: 0.4 ± 0.5% versus 2.6 ± 2.4%; P < 0.05 and 20%: 1.5 ± 2.7% versus 13.0 ± 18.7%; P < 0.01). This study demonstrates for the first time that S-NO-HSA promotes bone formation by slow NO release. Additionally, S-NO-HSA increases collagen sponge degradation. PMID:24113133

Fügl, A; Gasser, H; Watzak, G; Bucher, A; Feierfeil, J; Jürgens, G; Watzek, G; Hallström, S; Gruber, R

2014-03-01

215

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; 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

216

Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer  

PubMed Central

Purpose Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. Methods Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ?3 months of amenorrhea. Results Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm2 to 0.976 g/cm2 and 0.937 g/cm2 at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). Conclusions In what was likely a compensatory response to rapid bone loss, CIOF patients’ OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF. PMID:25575458

Oostra, Drew R.; Lustberg, Maryam B.; Reinbolt, Raquel E.; Pan, Xueliang; Wesolowski, Robert; Shapiro, Charles L.

2015-01-01

217

Bone changes occurring early after cessation of ovarian function in beagle dogs: a histomorphometric study employing sequential biopsies.  

PubMed

The beagle dog model has been established by our laboratory as a useful animal model to study bone loss after cessation of ovarian function. Previously we demonstrated bone loss associated with an osteoblastic insufficiency at 4 months after ovariohysterectomy (OHX). This study was designed to evaluate by four sequential monthly bone biopsies the development and course of the histologic bone abnormalities after OHX. We found cancellous bone volume, trabecular density, and wall thickness to be decreased (p less than 0.05) and trabecular separation increased (p less than 0.05) as early as 1 month after OHX. After 2 months, there was a decrease in mineralizing surface and mineral apposition rate (p less than 0.05). Volume and surface of osteoid were increased after 3 months (p less than 0.05), and there was an increase in the number of osteoblasts (p less than 0.01). No histologic signs of increased resorption were observed during the experiment. However, the findings of low bone volume with decreased trabecular density and increased separation without a change in trabecular plate thickness 4 weeks after OHX suggest that a dramatic increase in resorption must have taken place soon after OHX. These results point to an early phase of initiation of bone loss related to hyperresorption followed by a maintenance phase of low bone mass ascriblastic insufficiency. The events that stimulate the early initiating phase after cessation of ovarian function, the factors contributing to it, and the direct demonstration of hyperresorption await further studies. PMID:2333786

Faugere, M C; Friedler, R M; Fanti, P; Malluche, H H

1990-03-01

218

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. PMID:23874863

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

2013-01-01

219

Chondroid syringoma with extensive bone formation: a case report and review of the literature.  

PubMed

Chondroid syringoma is a rare, skin appendageal tumour, usually reported at the head and neck region. It is a mostly intradermal and rarely subcutaneous small painless nodule. The histopathological examination is characterized by a combination of epithelial and myoepithelial structures within a chondromyxoid and fibrous stroma. Herein, we present a rare case of chondroid syringoma with extensive bone formation. PMID:25478357

Bedir, Recep; Yurdakul, Cuneyt; Sehitoglu, Ibrahim; Gucer, Hasan; Tunc, Suphan

2014-10-01

220

Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones  

PubMed Central

Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography. PMID:25136480

Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

2014-01-01

221

Photothermal tomography for the functional and structural evaluation, and early mineral loss monitoring in bones.  

PubMed

Salient features of a new non-ionizing bone diagnostics technique, truncated-correlation photothermal coherence tomography (TC-PCT), exhibiting optical-grade contrast and capable of resolving the trabecular network in three dimensions through the cortical region with and without a soft-tissue overlayer are presented. The absolute nature and early demineralization-detection capability of a marker called thermal wave occupation index, estimated using the proposed modality, have been established. Selective imaging of regions of a specific mineral density range has been demonstrated in a mouse femur. The method is maximum-permissible-exposure compatible. In a matrix of bone and soft-tissue a depth range of ~3.8 mm has been achieved, which can be increased through instrumental and modulation waveform optimization. Furthermore, photoacoustic microscopy, a comparable modality with TC-PCT, has been used to resolve the trabecular structure and for comparison with the photothermal tomography. PMID:25136480

Kaiplavil, Sreekumar; Mandelis, Andreas; Wang, Xueding; Feng, Ting

2014-08-01

222

Sequential expression of osteoblast phenotypic genes during medullary bone formation and resorption in estrogen-treated male Japanese quails.  

PubMed

Medullary bone is formed reticularly in the bone marrow cavity of the long bones of female birds. Although this bone matrix contains fewer collagen fibers and more acid mucopolysaccharides than cortical bone, it is not clear that the expression pattern of osteoblast phenotypic genes during bone remodeling. Therefore, 17?-estradiol (E2)-treated male Japanese quails were used to examine the temporal expression patterns of osteoblast phenotypic genes, and to simultaneously confirm the morphological changes occurring in the bone marrow cavity during medullary bone formation and resorption. After E2 treatment, bone lining cells proliferated and developed into mature osteoblasts that had intense alkaline phosphatase (ALP) activity. These cells began to form medullary bone that contained acid mucopolysaccharides and tartrate-resistantacid phosphatase. Runt-related gene 2 (Runx2) mRNA was stably expressed throughout the process. The expression of both ALP and type I collagen mRNAs increased initially, and then rapidly decreased after day 7, while osteoclasts began to resorb medullary bone at day 5. The expression of bone matrix-related genes peaked at day 5, and suddenly decreased at day 7, except for osteopontin. Taken together with these results, the expression patterns of bone matrix-related genes during the later stages might be related to osteoclast activity. Additionally, the constant expression of Runx2 during bone formation and resorption suggested that osteoprogenitor cells always exist in the bone marrow cavity. Therefore, the expression patterns of these genes and the characteristics of bone matrix might extremely be related to the quick remodeling of medullary bone. PMID:22711567

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

2012-07-01

223

Premenopausal bone mineral content relates to height, weight and calcium intake during early adulthood.  

PubMed

The influence of dietary and anthropometric factors on bone mineral content was studied in 183 healthy premenopausal French-Canadian women aged between 40 and 50 years and living in the same area. Dietary evaluation of their calcium (Ca), caffeine and alcohol intake since the age of 20 was performed in all cases. Age, height, weight, exercise level, cigarette smoking, parity and estrogen were also recorded. Bone mineral content of the L2 to L4 vertebrae (BMCL, n = 183) and forearm (BMCF, n = 137) were measured respectively by dual and single photon absorptiometry. While stepwise regression analysis showed a significant relationship between total BMCL and height, weight and Ca intake, this only occurred with weight and Ca intake when BMCL was corrected for height of L2-L4 (BMCL/cm) or for bone scan area of L2-L4 (BMCL/cm2). BMCF expressed per unit of length correlated to height only. When subjects were divided into three groups according to their Ca intake (less than 500 mg/day, between 500 and 1000 mg/day and greater than 1000 mg/day), the mean BMC adjusted for significant covariables (height and weight) was statistically different for the low and high intake groups at both sites (BMCF, F = 3.9, P = 0.02; BMCL, F = 4.2, P less than 0.02; BMCL/cm, F = 6.1, P less than 0.005; BMCL/cm2, F = 4.4, P less than 0.02). These findings indicate that, of the variables considered, Ca intake, height and weight were the only significant factors related to bone mass in our homogeneous population. It is therefore suggested that Ca intake in early adulthood influences the axial and appendicular bone mass in premenopausal women. PMID:3191285

Picard, D; Ste-Marie, L G; Coutu, D; Carrier, L; Chartrand, R; Lepage, R; Fugère, P; D'Amour, P

1988-07-01

224

[Influence of high molecular weight polyethylene on viability of osteoblasts and new bone formation].  

PubMed

To investigate the influence of high molecular weight polyethylene (HMWP) on the viability of osteoblasts and new bone formation in the process of fracture healing, the osteoblasts derived from adult human bone marrow were cultured in HMWP maceration extract and normal culture medium. The viability of the osteoblasts was measured by MTT assay, and the function of the osteoblasts was detected by use of alkaline phosphatase test kit. The locked double-plating (steel plate and HMWP plate) was implanted and fixed at the artificial fracture of distal femur of dogs. Specimens were gained at 3, 6, 9 and 12 weeks postoperatively, examined with macroscopy, microscope and scanning electron microscope (SEM). The results showed that HMWP did no harm to osteoblasts. There is no significant difference in activities of proliferation and alkaline phosphatase between HMWP maceration extract and normal culture medium at each observation time of at 2,4,8, and 14 dyas (P>0. 05). Bone tissue under the implanted HMWP plate manifested no absorption; the new bones formed under the HMWP plate and gradually matured as time went on. It is demonstrated in this study that HMWP has no adverse influence on the viability of osteoblasts and new bone formation and it can be used as internal fixation implant in treating fractures. PMID:16532823

Ren, Gaohong; Lin, Angru; Pei, Guoxian; Hu, Basheng

2006-02-01

225

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

PubMed

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

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

2014-10-01

226

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. PMID:22879397

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

2012-01-01

227

mTORC2 Signaling Promotes Skeletal Growth and Bone Formation in Mice  

PubMed Central

Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase controlling many physiological processes in mammals. mTOR functions in two distinct protein complexes, namely mTORC1 and mTORC2. Compared to mTORC1, the specific roles of mTORC2 are less well understood. To investigate the potential contribution of mTORC2 to skeletal development and homeostasis, we have genetically deleted Rictor, an essential component of mTORC2, in the limb skeletogenic mesenchyme of the mouse embryo. Loss of Rictor leads to shorter and narrower skeletal elements in both embryos and postnatal mice. In the embryo, Rictor deletion reduces the width but not the length of the initial cartilage anlage. Subsequently, the embryonic skeletal elements are shortened due to a delay in chondrocyte hypertrophy, with no change in proliferation, apoptosis, cell size, or matrix production. Postnatally, Rictor-deficient mice exhibit impaired bone formation, resulting in thinner cortical bone, but the trabecular bone mass is relatively normal thanks to a concurrent decrease in bone resorption. Moreover, Rictor-deficient bones exhibit a lesser anabolic response to mechanical loading. Thus, mTORC2 signaling is necessary for optimal skeletal growth and bone anabolism. PMID:25196701

Chen, Jianquan; Holguin, Nilsson; Shi, Yu; Silva, Matthew J.; Long, Fanxin

2015-01-01

228

Reduced bone formation in non-steroid treated patients with rheumatoid arthritis.  

PubMed

The cellular basis of trabecular bone loss in rheumatoid arthritis was investigated in 45 non-steroid treated patients. Mean wall thickness, an indicator of the amount of bone formed per remodelling unit, mean interstitial bone thickness, which is related to resorption depth, and the extent of trabecular surface covered by osteoid, which reflects the number of remodelling units, were assessed in iliac crest biopsy specimens. The mean wall thickness was significantly reduced in the patient group when compared with controls matched for age and sex (mean (SD) 39.8 (5.4) v 51.6 (9.7) microns). There was no significant difference between patients and controls in the mean interstitial bone thickness (51.0 (26.4) v 61.4 (31.9) microns) or osteoid surface (16.7 (11.4) v 21.0 (10.5)%). These results show that reduced bone formation at the remodelling unit level is the predominant mechanism of bone loss in rheumatoid arthritis. PMID:2742402

Compston, J E; Vedi, S; Mellish, R W; Croucher, P; O'Sullivan, M M

1989-06-01

229

The Formation and Early Evolution of Young Massive Clusters  

NASA Astrophysics Data System (ADS)

We review the formation and early evolution of the most massive (> few 104 M?) and dense (radius of a few parsecs) young stellar clusters, focusing on the role that studies of these objects in our Galaxy can play in our understanding of star and planet formation as a whole. Comparing the demographics of young massive cluster (YMC) progenitor clouds and YMCs across the Galaxy shows that gas in the Galactic Center can accumulate to a high enough density that molecular clouds already satisfy the criteria used to define YMCs, without forming stars. In this case formation can proceed in situ — i.e., the stars form at protostellar densities close to the final stellar density. Conversely, in the disk, the gas either begins forming stars while it is being accumulated to high density, in a "conveyor belt" mode, or the timescale to accumulate the gas to such high densities must be much shorter than the star-formation timescale. The distinction between the formation regimes in the two environments is consistent with the predictions of environmentally dependent density thresholds for star formation. This implies that stars in YMCs of similar total mass and radius can have formed at widely different initial protostellar densities. The fact that no strong, systematic variations in fundamental properties (such as the IMF) are observed between YMCs in the disk and Galactic Center suggests that, statistically speaking, stellar mass assembly is not affected by the initial protostellar density. We then review recent theoretical advances and summarize the debate on three key open questions: the initial (proto)stellar distribution, infant (im)mortality, and age spreads within YMCs. We conclude that (1) the initial protostellar distribution is likely hierarchical, (2) YMCs likely experienced a formation history that was dominated by gas exhaustion rather than gas expulsion, (3) YMCs are dynamically stable from a young age, and (4) YMCs have age spreads much smaller than their mean age. Finally, we show that it is plausible that metal-rich globular clusters may have formed in a similar way to YMCs in nearby galaxies. In summary, the study of YMC formation bridges star/planet formation in the solar neighborhood to the oldest structures in the local universe.

Longmore, S. N.; Kruijssen, J. M. D.; Bastian, N.; Bally, J.; Rathborne, J.; Testi, L.; Stolte, A.; Dale, J.; Bressert, E.; Alves, J.

230

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

231

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

PubMed

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

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

2014-01-01

232

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

PubMed Central

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

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

2014-01-01

233

Golden bullet-denosumab: early rapid response of metastatic giant cell tumor of the bone.  

PubMed

Giant cell tumor of the bone (GCTB) is usually a benign, locally aggressive tumor with metastatic potential. Histogenesis of GCTB is unknown and a correlation has not been found between histologic and clinical course. For this reason, many authors consider its prognosis unpredictable. Lung metastasis after GCTB treatment is well known and generally has unfavorable outcome, despite varied chemotherapy regimens. Denosumab, which inhibits RANK-RANKL interaction, is a new, promising actor among targeted therapeutic agents for GCTB. In this report, we emphasize on early rapid response to denosumab in metastatic GCTB. PMID:24072245

Demirsoy, Ugur; Karadogan, Meriban; Selek, Özgür; Anik, Yonca; Aksu, Görkem; Müezzinoglu, Bahar; Corapcioglu, Funda

2014-03-01

234

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. PMID:20962189

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

235

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation  

PubMed Central

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

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

2012-01-01

236

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

237

Bmpr1a signaling plays critical roles in palatal shelf growth and palatal bone formation  

PubMed Central

Cleft palate, including submucous cleft palate, is among the most common birth defects in humans. While overt cleft palate results from defects in growth or fusion of the developing palatal shelves, submucous cleft palate is characterized by defects in palatal bones. In this report, we show that the Bmpr1a gene, encoding a type I receptor for bone morphogenetic proteins (Bmp), is preferentially expressed in the primary palate and anterior secondary palate during palatal outgrowth. Following palatal fusion, Bmpr1a mRNA expression was upregulated in the condensed mesenchyme progenitors of palatal bone. Tissue-specific inactivation of Bmpr1a in the developing palatal mesenchyme in mice caused reduced cell proliferation in the primary and anterior secondary palate, resulting in partial cleft of the anterior palate at birth. Expression of Msx1 and Fgf10 was downregulated in the anterior palate mesenchyme and expression of Shh was downregulated in the anterior palatal epithelium in the Bmpr1a conditional mutant embryos, indicating that Bmp signaling regulates mesenchymal-epithelial interactions during palatal outgrowth. In addition, formation of the palatal processes of the maxilla was blocked while formation of the palatal processes of the palatine was significantly delayed, resulting in submucous cleft of the hard palate in the mutant mice. Our data indicate that Bmp signaling plays critical roles in the regulation of palatal mesenchyme condensation and osteoblast differentiation during palatal bone formation. PMID:21185278

Baek, Jin-A; Lan, Yu; Liu, Han; Maltby, Kathleen M.; Mishina, Yuji; Jiang, Rulang

2011-01-01

238

Insulin promotes bone formation in augmented maxillary sinus in diabetic rabbits.  

PubMed

The role of insulin during the formation of bone in the augmented space of the maxillary sinus in patients with diabetes is unclear. The authors compared the differences in bone formation after maxillary sinus floor elevation in diabetic and healthy animals and evaluated the effects of insulin on osteogenesis and the differentiation and activities of the osteoblasts. 10 male Japanese white rabbits were divided into two groups after diabetic induction by a single injection of monohydrated alloxan and having maintained steady blood glucose levels. The groups included the diabetes mellitus group (DM; n=5) and the DM+insulin group (n=5); another five healthy rabbits comprised the control group. Maxillary sinus floor elevation was performed by grafting hydroxyapatite particles. Compared with the control group, the newly formed bone area, number of blood vessels and osteoblasts, collagen I content and serum osteocalcin levels were significantly decreased in DM rabbits (P<0.01). Insulin treatment reversed the decrease in bone formation, blood vessels, osteoblasts, collagen I and serum osteocalcin (P<0.01). Insulin treatment also promoted osteogenesis in the augmented space of the diabetic rabbits, which might have resulted from promotion of osteoblast differentiation and upregulation of neovascularization. PMID:22099315

Hou, C-J; Liu, J-L; Li, X; Bi, L-J

2012-03-01

239

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

PubMed Central

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

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

2013-01-01

240

Phosvitin phosphorus is involved in chicken embryo bone formation through dephosphorylation.  

PubMed

The aim of this study was to investigate the role of phosvitin in bone formation in chicken embryos. The yolk P content, P/N ratio and secondary structure of phosvitin, alkaline phosphatase (ALP) activity of the tibia, and body length were determined during incubation. A high correlation was found between the phosphate group content of phosvitin and both secondary structure and bone metabolism (ALP activity in the tibia, body length). The ALP activity and body length growth slightly lagged behind changes in the P/N ratio and the secondary structure of phosvitin. The phosphate content of phosvitin decreased, the ?-random coil and ?-turn gradually transformed into ?-helixes, and the secondary structure of protein tended to become more orderly; these changes mainly occurred on d 13 to 16. Bone formation of the chicken embryos occurred primarily on d 14 to 18, whereas ALP activity and body length growth increased substantially. The results indicate that phosvitin P is involved in chicken embryo bone formation through dephosphorylation. PMID:25352680

Li, Chunyan; Geng, Fang; Huang, Xi; Ma, Meihu; Zhang, Xiaowei

2014-12-01

241

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

PubMed Central

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

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

2013-01-01

242

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation.  

PubMed

Recapitulation of endochondral ossification leads to a new concept of bone tissue engineering via a cartilage intermediate as an osteoinductive template. In this study, we aimed to investigate the influence of in vitro chondrogenic priming time for the creation of cartilage template on the in vivo endochondral bone formation both qualitatively and quantitatively. To this end, rat bone-marrow-derived mesenchymal stromal cells (MSCs) were seeded onto two scaffolds with distinguished features: a fibrous poly(lactic-co-glycolic acid)/poly(?-caprolactone) electrospun scaffold (PLGA/PCL) and a porous hydroxyapatite/tricalcium phosphate composite (HA/TCP). The constructs were then chondrogenically differentiated for 2, 3 and 4weeks in vitro, followed by subcutaneous implantation in vivo for up to 8weeks. A longer chondrogenic priming time resulted in a significantly increased amount and homogeneous deposition of the cartilage matrix on both the PLGA/PCL and HA/TCP scaffolds in vitro. In vivo, all implanted constructs gave rise to endochondral bone formation, whereas the bone volume was not affected by the length of priming time. An unpolarized woven bone-like structure, with significant amounts of cartilage remaining, was generated in fibrous PLGA/PCL scaffolds, while porous HA/TCP scaffolds supported progressive lamellar-like bone formation with mature bone marrow development. These data suggest that, by utilizing a chondrogenically differentiated MSC-scaffold construct as cartilage template, 2weeks of in vitro priming time is sufficient to generate a substantial amount of vascularized endochondral bone in vivo. The structure of the bone depends on the chemical and structural cues provided by the scaffold design. PMID:25463490

Yang, Wanxun; Both, Sanne K; van Osch, Gerjo J V M; Wang, Yining; Jansen, John A; Yang, Fang

2015-02-01

243

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

244

Hypoxia-inducible Factor-1? Protein Negatively Regulates Load-induced Bone Formation*  

PubMed Central

Mechanical loads induce profound anabolic effects in the skeleton, but the molecular mechanisms that transduce such signals are still poorly understood. In this study, we demonstrate that the hypoxia-inducible factor-1? (Hif-1?) is acutely up-regulated in response to exogenous mechanical stimuli secondary to prostanoid signaling and Akt/mTOR (mammalian target of rapamycin) activation. In this context, Hif-1? associates with ?-catenin to inhibit Wnt target genes associated with bone anabolic activity. Mice lacking Hif-1? in osteoblasts and osteocytes form more bone when subjected to tibia loading as a result of increased osteoblast activity. Taken together, these studies indicate that Hif-1? serves as a negative regulator of skeletal mechanotransduction to suppress load-induced bone formation by altering the sensitivity of osteoblasts and osteocytes to mechanical signals. PMID:22081627

Riddle, Ryan C.; Leslie, Julie M.; Gross, Ted S.; Clemens, Thomas L.

2011-01-01

245

ORIGINAL ARTICLE JBMR Unique Roles of Phosphorus in Endochondral Bone Formation and Osteocyte Maturation  

E-print Network

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

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

246

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

Microsoft Academic Search

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

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

2006-01-01

247

TWIST1 expression in breast cancer cells facilitates bone metastasis formation.  

PubMed

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

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

2014-08-01

248

Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL.  

PubMed

The high complete remission rate with first-line combined fludarabine, cyclophosphamide, and rituximab (FCR) begs the question of the value of minimal residual disease (MRD)-negative status as a treatment end point. We report on 237 patients with chronic lymphocytic leukemia who received first-line FCR. MRD was prospectively assessed by 4-color flow cytometry in bone marrow after course 3 and at final response assessment. After course 3 and at final response assessment, 17% and 43% of patients were MRD negative in bone marrow, respectively. A mutated immunoglobulin heavy chain variable gene and trisomy 12 were independently associated with MRD-negative status both after 3 courses of FCR and at final response assessment in multivariable analyses (MVAs). MRD-negative status was independently associated with significantly longer progression-free survival (PFS) and overall survival (OS) in MVA (P = .03 and .02, respectively). This association was confirmed also on landmark MVA at the time of MRD assessment (P = .04 and .05, respectively). MRD-negative patients had comparable PFS and OS, independent of the number of courses received or interim staging. Early MRD eradication may be a desirable goal, prompting consideration of early discontinuation of treatment. This trial was registered at www.clinicaltrials.gov as #NCT00759798. PMID:24705492

Strati, Paolo; Keating, Michael J; O'Brien, Susan M; Burger, Jan; Ferrajoli, Alessandra; Jain, Nitin; Tambaro, Francesco Paolo; Estrov, Zeev; Jorgensen, Jeffrey; Challagundla, Pramoda; Faderl, Stefan H; Wierda, William G

2014-06-12

249

Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: Early treatment rescues bone lesions?  

PubMed

We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology [1]. To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in the liver and spleen, with detectable activity in the bone and brain. Second, newborn ERT was conducted after a tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th weeks were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in the liver and spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than that in adult mice treated with ERT; however, hyaline and fibrous cartilage cells in the femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mice. PMID:24953405

Tomatsu, Shunji; Montaño, Adriana M; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Gutiérrez, Monica L; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S

2015-02-01

250

Simulated resistance training, but not alendronate, increases cortical bone formation and suppresses sclerostin during disuse.  

PubMed

Mechanical loading modulates the osteocyte-derived protein sclerostin, a potent inhibitor of bone formation. We hypothesized that simulated resistance training (SRT), combined with alendronate (ALEN) treatment, during hindlimb unloading (HU) would most effectively mitigate disuse-induced decrements in cortical bone geometry and formation rate (BFR). Sixty male, Sprague-Dawley rats (6-mo-old) were randomly assigned to either cage control (CC), HU, HU plus either ALEN (HU+ALEN), or SRT (HU+SRT), or combined ALEN and SRT (HU+SRT/ALEN) for 28 days. Computed tomography scans on days -1 and 28 were taken at the middiaphyseal tibia. HU+SRT and HU+SRT/ALEN rats were subjected to muscle contractions once every 3 days during HU (4 sets of 5 repetitions; 1,000 ms isometric + 1,000 ms eccentric). The HU+ALEN and HU+SRT/ALEN rats received 10 ?g/kg ALEN 3 times/wk. Compared with the CC animals, HU suppressed the normal slow growth-induced increases of cortical bone mineral content, cortical bone area, and polar cross-sectional moment of inertia; however, SRT during HU restored cortical bone growth. HU suppressed middiaphyseal tibia periosteal BFR by 56% vs. CC (P < 0.05). However, SRT during HU restored BFR at both periosteal (to 2.6-fold higher than CC) and endocortical (14-fold higher than CC) surfaces (P < 0.01). ALEN attenuated the SRT-induced BFR gains during HU. The proportion of sclerostin-positive osteocytes in cortical bone was significantly higher (+121% vs. CC) in the HU group; SRT during HU effectively suppressed the higher proportion of sclerostin-positive osteocytes. In conclusion, a minimum number of high-intensity muscle contractions, performed during disuse, restores cortical BFR and suppress unloading-induced increases in sclerostin-positive osteocytes. PMID:22174402

Macias, B R; Swift, J M; Nilsson, M I; Hogan, H A; Bouse, S D; Bloomfield, S A

2012-03-01

251

Use of cultivated osteoprogenitor cells to increase bone formation in segmental mandibular defects: an experimental pilot study in sheep.  

PubMed

The hypothesis of the present experimental pilot study was that autogeneous cultivated osteoprogenitor cells in porous calcium phosphate scaffolds can increase bone formation in segmental defects of the mandible. The autogenous osteoprogenitor cells of eight sheep were cultivated from bone biopsies from the iliac crest and seeded into cylindrical scaffolds of pyrolized bovine bone of an overall length of 35 mm and 13 mm in diameter. Segmental defects of 35 mm length were created unilaterally in the mandibles of the animals. Reconstruction was performed using cylinders with cultivated osteoprogenitor cells in four animals and empty scaffolds in the remaining four sheep, which served as controls. After 5 months, the mandibles were retrieved and the reconstructed areas were analyzed by qualitative and quantitative histology in serial undecalcified thick-section specimens. There was significantly more bone formation in the group that had received scaffolds with cultivated bone cells (P=0.028). Bone formation was present in 34.4% of the evaluated cross-sectional units in the seeded scaffolds, while it was found in 10.4% in the control group. Although the spatial distribution of bone formation was significantly different across the scaffold in both groups, osteoprogenitor cells appeared to have increased bone formation, particularly in the centre of the defect when compared to the control group. It is concluded that the repair of segmental defects of the mandible can be enhanced by the transplantation of autogenous osteoprogenitor cells in a porous calcium phosphate scaffold. PMID:11829236

Schliephake, H; Knebel, J W; Aufderheide, M; Tauscher, M

2001-12-01

252

Bone formation in algae-derived and synthetic calcium phosphates with or without poloxamer.  

PubMed

Calcium phosphate ceramics such as hydroxyapatite (HA) and biphasic calcium phosphates are used clinically to repair bone defects. These calcium phosphate ceramics can differ by composition, structure, and rate of degradation. This study compared 3 calcium phosphate ceramics, 2 of which have similar structure but different composition: 100% HA (algae derived) and HA/?-tricalcium phosphate (?-TCP) 20/80 (algae derived), and 2 with different structure but similar composition: HA/?-TCP 20/80 (algae derived) and HA/?-TCP 15/85 (synthetic). Calcium phosphate ceramics can be difficult to handle and contour during the surgeries. To improve handling, Poloxamer 407 (P407) was added to the 3 ceramics, and its effect on bone healing was also assessed. Bilateral calvarial defects created in the parietal bones of New Zealand white rabbits were left unfilled or were filled with autograft or one of the ceramics, with and without P407. Six weeks after operation, healing was evaluated qualitatively by histology and quantitatively by micro-computed tomography analysis and histomorphometry. All 3 calcium phosphate ceramics demonstrated osteoconductivity and performed similarly in supporting new bone formation, suggesting that the differences in their composition, structure, or degradation did not significantly affect their ability to promote bone healing in this application. Incorporating P407 did not impede osteoconductivity as HA and biphasic calcium phosphate combined with P407 performed similarly as when used alone for craniofacial defect repair. PMID:23524692

Zhou, Aileen Jing-Jing; Clokie, Cameron Malcolm Lang; Peel, Sean Alexander Fitzgerald

2013-03-01

253

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

254

Twist1- and Twist2-Haploinsufficiency Results in Reduced Bone Formation  

PubMed Central

Background Twist1 and Twist2 are highly homologous bHLH transcription factors that exhibit extensive highly overlapping expression profiles during development. While both proteins have been shown to inhibit osteogenesis, only Twist1 haploinsufficiency is associated with the premature synostosis of cranial sutures in mice and humans. On the other hand, biallelic Twist2 deficiency causes only a focal facial dermal dysplasia syndrome or additional cachexia and perinatal lethality in certain mouse strains. It is unclear how these proteins cooperate to synergistically regulate bone formation. Methods Twist1 floxed mice (Twist1f/f) were bred with Twist2-Cre knock-in mice (Twist2Cre/+) to generate Twist1 and Twist2 haploinsufficient mice (Twist1f/+; Twist2Cre/+). X-radiography, micro-CT scans, alcian blue/alizarin red staining, trap staining, BrdU labeling, immunohistochemistry, in situ hybridizations, real-time PCR and dual luciferase assay were employed to investigate the overall skeletal defects and the bone-associated molecular and cellular changes of Twist1f/+;Twist2Cre/+ mice. Results Twist1 and Twist2 haploinsufficient mice did not present with premature ossification and craniosynostosis; instead they displayed reduced bone formation, impaired proliferation and differentiation of osteoprogenitors. These mice exhibited decreased expressions of Fgf2 and Fgfr1–4 in bone, resulting in a down-regulation of FGF signaling. Furthermore, in vitro studies indicated that both Twist1 and Twist2 stimulated 4.9 kb Fgfr2 promoter activity in the presence of E12, a Twist binding partner. Conclusion These data demonstrated that Twist1- and Twist2-haploinsufficiency caused reduced bone formation due to compromised FGF signaling. PMID:24971743

Huang, Yanyu; Meng, Tian; Wang, Suzhen; Zhang, Hua; Mues, Gabriele; Qin, Chunlin; Feng, Jian Q.; D'Souza, Rena N.; Lu, Yongbo

2014-01-01

255

Bone reactions to early occlusal loading of two-stage titanium plasma-sprayed implants: a pilot study in monkeys.  

PubMed

This pilot study analyzed the bone reactions to early loaded titanium plasma-sprayed implants. A total of 24 titanium plasma-sprayed implants (12 in the maxilla and 12 in the mandible) (Primary Healing Implant, Legnano) were inserted into four Macaca fascicularis monkeys with instruments specially designed to obtain a precise fit of the implant in the bone socket. A metal superstructure was cemented into 10 mandibular and 10 maxillary implants 15 days after implant insertion. The four remaining implants were used as controls. Eight months after implant placement, a block section was carried out, the defect was filled with nonresorbable hydroxyapatite, and all 24 implants were retrieved. The implants were treated to obtain thin ground sections that were examined under normal and polarized light. Histologic analysis showed that bone was observed around the implant surface in all implants. Morphometric analysis demonstrated that bone lined 67.2% (SD = 3.1%) of the maxillary implant surface, and 80.71% (SD = 4.6%) of the mandibular implant surface. No differences were found in the percentage of bone-implant contact in the control implants. In the loaded implants, however, the bone around the implants had a more compact appearance. The study demonstrated that it is possible to obtain a high percentage of bone-implant contact in early loaded titanium plasma-sprayed implants. PMID:9497710

Piattelli, A; Corigliano, M; Scarano, A; Quaranta, M

1997-04-01

256

Early sensing of Yersinia pestis airway infection by bone marrow cells  

PubMed Central

Bacterial infection of the lungs triggers a swift innate immune response that involves the production of cytokines and chemokines that promote recruitment of immune cells from the bone marrow (BM) into the infected tissue and limit the ability of the pathogen to replicate. Recent in vivo studies of pneumonic plague in animal models indicate that the pulmonary pro-inflammatory response to airway infection with Yersinia pestis is substantially delayed in comparison to other pathogens. Consequently, uncontrolled proliferation of the pathogen in the lungs is observed, followed by dissemination to internal organs and death. While the lack of an adequate early immune response in the lung is well described, the response of BM-derived cells is poorly understood. In this study, we show that intranasal (i.n.) infection of mice with a fully virulent Y. pestis strain is sensed early by the BM compartment, resulting in a reduction in CXCR4 levels on BM neutrophils and their subsequent release into the blood 12 hours (h) post infection. In addition, increased levels of BM-derived hematopoietic stem and progenitor cells (HSPC) were detected in the blood early after infection. Mobilization of both immature and mature cells was accompanied by the reduction of BM SDF-1 (CXCL-12) levels and the reciprocal elevation of SDF-1 in the blood 24 h post infection. RT-PCR analysis of RNA collected from total BM cells revealed an early induction of myeloid-associated genes, suggesting a prompt commitment to myeloid lineage differentiation. These findings indicate that lung infection by Y. pestis is sensed by BM cells early after infection, although bacterial colonization of the BM occurs at late disease stages, and point on a potential cross-talk between the lung and the BM at early stages of pneumonic plague. PMID:23189271

Vagima, Yaron; Levy, Yinon; Gur, David; Tidhar, Avital; Aftalion, Moshe; Abramovich, Hagar; Zahavy, Eran; Zauberman, Ayelet; Flashner, Yehuda; Shafferman, Avigdor; Mamroud, Emanuelle

2012-01-01

257

Widespread formation of cherts during the early Eocene climate optimum  

NASA Astrophysics Data System (ADS)

Radiolarian cherts in the Tethyan realm of Jurassic age were recently interpreted as resulting from high biosiliceous productivity along upwelling zones in subequatorial paleolatitudes the locations of which were confirmed by revised paleomagnetic estimates. However, the widespread occurrence of cherts in the Eocene suggests that cherts may not always be reliable proxies of latitude and upwelling zones. In a new survey of the global spatiotemporal distribution of Cenozoic cherts in Deep Sea Drilling Project (DSDP) and Ocean Drilling Program (ODP) sediment cores, we found that cherts occur most frequently in the Paleocene and early Eocene, with a peak in occurrences at ~50 Ma that is coincident with the time of highest bottom water temperatures of the early Eocene climatic optimum (EECO) when the global ocean was presumably characterized by reduced upwelling efficiency and biosiliceous productivity. Cherts occur less commonly during the subsequent Eocene global cooling trend. Primary paleoclimatic factors rather than secondary diagenetic processes seem therefore to control chert formation. This timing of peak Eocene chert occurrence, which is supported by detailed stratigraphic correlations, contradicts currently accepted models that involve an initial loading of large amounts of dissolved silica from enhanced weathering and/or volcanism in a supposedly sluggish ocean of the EECO, followed during the subsequent middle Eocene global cooling by more vigorous oceanic circulation and consequent upwelling that made this silica reservoir available for enhanced biosilicification, with the formation of chert as a result of biosilica transformation during diagenesis. Instead, we suggest that basin-basin fractionation by deep-sea circulation could have raised the concentration of EECO dissolved silica especially in the North Atlantic, where an alternative mode of silica burial involving widespread direct precipitation and/or absorption of silica by clay minerals could have been operative in order to maintain balance between silica input and output during the upwelling-deficient conditions of the EECO. Cherts may therefore not always be proxies of biosiliceous productivity associated with latitudinally focused upwelling zones.

Muttoni, G.; Kent, D. V.

2007-12-01

258

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

259

Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry  

Microsoft Academic Search

The effects of dietary vitamin E (VIT E) and lipids on tissue lipid peroxidation and fatty acid composition, epiphyseal growth plate cartilage development, and trabecular bone formation were evaluated in chicks. A 2×2 factorial design was followed using two levels (30 and 90 IU\\/kg of diet) of dl-?-tocopheryl acetate and two different dietary lipids. The basal semipurified diet contained one

H. Xu; B. A. Watkins; M. F. Seifert

1995-01-01

260

Early-type galaxy star formation histories in different environments  

NASA Astrophysics Data System (ADS)

We use very high signal-to-noise ratio stacked spectra of ˜29 000 nearby quiescent early-type galaxies (ETGs) from the Sloan Digital Sky Survey to investigate variations in their star formation histories (SFHs) with environment at fixed position along and perpendicular to the Fundamental Plane. We define three classifications of local group environment based on the `identities' of galaxies within their dark matter haloes: central `Brightest Group Galaxies' (BGGs); Satellites; and Isolateds (those `most massive' in a dark matter halo with no Satellites). We find that the SFHs of quiescent ETGs are almost entirely determined by their structural parameters ? and ?Ie. Any variation with local group environment at fixed structure is only slight: Satellites have the oldest stellar populations, 0.02 dex older than BGGs and 0.04 dex older than Isolateds; differences in Fe enrichment with local group environment are consistent with zero (<2?); there are no differences in Mg enhancement between BGGs, Isolateds, and Satellites. Our observation that, to zeroth-order, the SFHs of quiescent ETGs are fully captured by their structures places important qualitative constraints on the degree to which late-time evolutionary processes (those which occur after a galaxy's initial formation and main star-forming lifetime) can alter their SFHs/structures.

Fitzpatrick, Patrick J.; Graves, Genevieve J.

2015-02-01

261

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

PubMed

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. PMID:23174338

Tazi, Neftaha; Zhang, Ze; Messaddeq, Younès; Almeida-Lopes, Luciana; Zanardi, Lisinéia M; Levinson, Dennis; Rouabhia, Mahmoud

2012-01-01

262

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. PMID:23174338

2012-01-01

263

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

Microsoft Academic Search

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

MURALI JASTY; STEVEN SCHUTZER; JOEL TEPPER; CHRISTOPHER WILLETT; MICHAEL A. STRACHER; WILLIAM H. HARRIS

1990-01-01

264

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

PubMed Central

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

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

2014-01-01

265

Dark Matter Heating and Early Core Formation in Dwarf Galaxies  

NASA Astrophysics Data System (ADS)

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

Madau, Piero; Shen, Sijing; Governato, Fabio

2014-07-01

266

In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc  

NASA Astrophysics Data System (ADS)

Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

McCanless, Jonathan D.

267

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

PubMed

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

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

2013-09-01

268

Talking among ourselves: paracrine control of bone formation within the osteoblast lineage.  

PubMed

While much research focuses on the range of signals detected by the osteoblast lineage that originate from endocrine influences, or from other cells within the body, there are also multiple interactions that occur within this family of cells. Osteoblasts exist as teams and form extensive communication networks both on, and within, the bone matrix. We provide four snapshots of communication pathways that exist within the osteoblast lineage between different stages of their differentiation, as follows: (1) PTHrP, a factor produced by early osteoblasts that stimulates the activity of more mature bone-forming cells and the most mature osteoblast embedded within the bone matrix, the osteocyte; (2) sclerostin, a secreted factor, released by osteocytes into their extensive communication network to restrict the activity of younger osteoblasts on the bone surface; (3) oncostatin M, a member of the IL-6/gp130 family of cytokines, expressed throughout osteoblast differentiation and acting to stimulate osteoblast activity that works on a different receptor in the mature osteocyte compared to the preosteoblast; and (4) Eph/ephrins, cell-contact-dependent kinases, and the osteoblast-lineage-specific interaction of EphB4 and ephrinB2, which provides a checkpoint for entry to the late stages of osteoblast differentiation and restricts RANKL expression. PMID:23695526

Tonna, Stephen; Sims, Natalie A

2014-01-01

269

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

270

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

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

271

Bone Mineral Density and Body Composition before and during Treatment with Gonadotropin-Releasing Hormone Agonist in Children with Central Precocious and Early Puberty  

Microsoft Academic Search

Major changes in bone mineral density (BMD) and body composi- tion occur during puberty. In the present longitudinal study, we eval- uated BMD and calculated volumetric BMD (bone mineral apparent density (BMAD)), bone metabolism, and body composition of children (32 girls and 2 boys) with central precocious and early puberty before and during treatment with GnRH agonist (GnRH). Patients were

ANNEMIEKE M. BOOT; MUINCK KEIZER-SCHRAMA; HUIBERT A. P. POLS; ERIC P. KRENNING; STENVERT L. S. DROP

272

EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.  

PubMed

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-? (HIF-?) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration. PMID:25003898

Wan, Lin; Zhang, Fengjie; He, Qiling; Tsang, Wing Pui; Lu, Li; Li, Qingnan; Wu, Zhihong; Qiu, Guixing; Zhou, Guangqian; Wan, Chao

2014-01-01

273

EPO Promotes Bone Repair through Enhanced Cartilaginous Callus Formation and Angiogenesis  

PubMed Central

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-? (HIF-?) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration. PMID:25003898

Wan, Lin; Zhang, Fengjie; He, Qiling; Tsang, Wing Pui; Lu, Li; Li, Qingnan; Wu, Zhihong; Qiu, Guixing; Zhou, Guangqian; Wan, Chao

2014-01-01

274

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

PubMed

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

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

2013-03-01

275

Trabecular bone anisotropy and orientation in an Early Pleistocene hominin talus from East Turkana, Kenya.  

PubMed

Among the structural properties of trabecular bone, the degree of anisotropy is most often found to separate taxa with different habitual locomotor modes. This study examined the degree of anisotropy, the elongation, and primary orientation of trabecular bone in the KNM-ER 1464 Early Pleistocene hominin talus as compared with extant hominoid taxa. Modern human tali were found to have a pattern of relatively anisotropic and elongated trabeculae on the lateral aspect, which was not found in Pan, Gorilla, Pongo, or KNM-ER 1464. Trabecular anisotropy in the fossil talus most closely resembled that of the African apes except for a region of high anisotropy in the posteromedial talus. The primary orientation of trabeculae in the anteromedial region of KNM-ER 1464 was strikingly different from that of the great apes and very similar to that of modern humans in being directed parallel to the talar neck. These results suggest that, relative to that of modern humans, the anteromedial region of the KNM-ER 1464 talus may have transmitted body weight to the midfoot in a similar manner while the lateral aspect may have been subjected to more variable loading conditions. PMID:23601236

Su, Anne; Wallace, Ian J; Nakatsukasa, Masato

2013-06-01

276

Copal bone cement is more effective in preventing biofilm formation than Palacos R-G.  

PubMed

Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G. PMID:18338216

Ensing, Geert T; van Horn, Jim R; van der Mei, Henny C; Busscher, Henk J; Neut, Daniëlle

2008-06-01

277

Copal Bone Cement Is More Effective in Preventing Biofilm Formation than Palacos R-G  

PubMed Central

Bone cements loaded with combinations of antibiotics are assumed more effective in preventing infection than bone cements with gentamicin as a single drug. Moreover, loading with an additional antibiotic may increase interconnectivity between antibiotic particles to enhance release. We hypothesize addition of clindamycin to a gentamicin-loaded cement yields higher antibiotic release and causes larger inhibition zones against clinical isolates grown on agar and stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone cement was more extensive (65% of the clindamycin and 41% of the gentamicin incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The higher antibiotic release from Copal resulted in a stronger and more prolonged inhibition of bacterial growth on agar. Bacterial colony counting and confocal laser scanning microscopy of biofilms grown on the bone cements suggest antibiotic release reduced bacterial viability, most notably close to the cement surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin-resistant small colony variants on Palacos R-G and therefore Copal more effectively decreased biofilm formation than Palacos R-G. PMID:18338216

Ensing, Geert T.; van Horn, Jim R.; van der Mei, Henny C.; Busscher, Henk J.

2008-01-01

278

Inhibition of bone resorption by divided-dose calcium supplementation in early postmenopausal women.  

PubMed

We have previously shown that a calcium (Ca) supplement of 1000 mg given in the evening reduces the overnight and early morning, but not the daytime, excretion of bone resorption markers in postmenopausal women within five years of the menopause. In the present study, we have looked at the effect of splitting the Ca into two doses of 500 mg each given in the morning and evening. We studied 19 healthy women (median age 53 years) who were all within 5 years of the menopause. On the 2 study days, urine was collected from 9 a.m. to 9 p.m. (day collection), and from 9 p.m. to 9 a.m. (night collection); a further fasting (spot) urine sample was obtained at 9 a.m. at the end of the night collection. The first day was a control day; on the second day the subjects ingested 500 mg Ca as the carbonate at 9 a.m. and 9 p.m. We measured pyridinoline cross-links excretion in all the samples, as well as hydroxyproline in the fasting urine. The Ca supplements lowered urinary excretion of the markers during the day (P < 0.01), had only a marginal effect during the night, but reduced excretion significantly in the fasting urine (P < 0.001). In the whole 24-hour period, the falls in resorption markers were small but comparable to those seen after the ingestion of 1 g of Ca in the evening. We conclude that the acute administration of 0.5 g Ca in the morning and evening reduced the markers of bone resorption in early postmenopausal women during the day but not during the following night, whereas the single 1 g supplement had the reverse effect. Over the 24-hour period, there was nothing to choose between the two regimes. Women at this stage in their life cycle probably require a larger Ca supplement if they are not taking estrogen. PMID:11289691

Scopacasa, F; Need, A G; Horowitz, M; Wishart, J M; Morris, H A; Nordin, B E

2000-12-01

279

Osteoclastic activity begins early and increases over the course of bone healing  

Microsoft Academic Search

Osteoclasts are specialised bone-resorbing cells. This particular ability makes osteoclasts irreplaceable for the continual physiological process of bone remodelling as well as for the repair process during bone healing. Whereas the effects of systemic diseases on osteoclasts have been described by many authors, the spatial and temporal distribution of osteoclasts during bone healing seems to be unclear so far.In the

Hanna Schell; Jasmin Lienau; Devakara R. Epari; Petra Seebeck; Christine Exner; Sarah Muchow; Hermann Bragulla; Norbert P. Haas; Georg N. Duda

2006-01-01

280

Local inhibition of 5-lipoxygenase enhances bone formation in a rat model  

PubMed Central

Objectives Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis. Methods Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days. Results Using micro-CT, we found that A-79175, a 5-LO inhibitor, increased bone formation in an apparent dose-related manner. Conclusions These results indicate that 5-LO inhibition could be used therapeutically to enhance treatments that require the direct formation of bone. PMID:23610701

Cottrell, J. A.; Keshav, V.; Mitchell, A.; O’Connor, J. P.

2013-01-01

281

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

PubMed Central

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

Zhang, Jianying; Wang, James H-C

2014-01-01

282

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

PubMed

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

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

2014-10-01

283

Sex differences in trabecular bone microarchitecture are not detected in pre and early pubertal children using magnetic resonance imaging  

PubMed Central

Introduction Sex differences in trabecular bone microarchitecture have been reported in adults and adolescents, but studies in children are lacking. The primary aim of this study was to determine if there are sex differences in magnetic resonance imaging (MRI)-based measures of trabecular bone microarchitecture at the distal femur of children. Materials and methods Pre and early pubertal boys (n = 23) and girls (n = 20) between the 5th and 95th percentiles for height, body mass and BMI were studied. Apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th), trabecular separation (appTb.Sp) and a composite measure of trabecular bone microarchitecture (TBMcom) were assessed at the lateral aspect of the distal femur using MRI. Areal bone mineral density (aBMD), bone mineral content (BMC) and bone area were assessed at the distal femur using dual-energy X-ray absorptiometry (DXA). Tanner staging was used to assess pubertal development. Physical activity was assessed using an accelerometry-based activity monitor. Calcium intake was assessed using diet records. Results There were no sex differences in age, height, femur length, body mass, physical activity or calcium intake (all P > 0.05). There were no sex differences in any MRI-based measure of trabecular bone microarchitecture. Consistent with the MRI-based measures, there were no differences in aBMD, BMC or bone area at the distal femur (P > 0.05). appBV/TV, appTb.N, appTb.Th, appTb.Sp and TBMcom were also moderately to strongly related to aBMD (r = 0.73, 0.63, 0.51, -0.74 and 0.61, respectively, p < 0.001) and BMC (r = 0.84, 0.63, 0.66, -0.80 and 0.77, respectively, P < 0.001). Conclusions The findings suggest that there are no differences in measures of trabecular bone microarchitecture at the distal femur of pre and early pubertal boys and girls who are similar in size, physical activity and calcium intake. Future studies with larger sample sizes that cover all pubertal stages are needed to determine if sex differences in trabecular bone microarchitecture emerge at the distal femur and other weight bearing bone sites. PMID:21851868

Modlesky, Christopher M.; Bajaj, Deepti; Kirby, Joshua T.; Mulrooney, Brianne M.; Rowe, David A.; Miller, Freeman

2011-01-01

284

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

E-print Network

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

Paris-Sud XI, Université de

285

Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin  

Microsoft Academic Search

Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling

A Bacigalupo; R Oneto; B Bruno; M Soracco; T Lamparelli; F Gualandi; D Occhini; AM Raiola; N Mordini; G Berisso; S Bregante; G Dini; A Lombardi; MT Van Lint; R Brand

1999-01-01

286

COPYRIGHT 2005 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED Early Tension Loss in an Anterior  

E-print Network

COPYRIGHT © 2005 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED 381 Early Tension Loss washer, double staples, a bioabsorbable interference screw, and a WasherLoc). Three cyclic loading.0001), 64% for the interference screw (p = 0.0001), and 56% for the WasherLoc (p

Hull, Maury

287

A soluble bone morphogenetic protein type IA receptor increases bone mass and bone strength  

PubMed Central

Diseases such as osteoporosis are associated with reduced bone mass. Therapies to prevent bone loss exist, but there are few that stimulate bone formation and restore bone mass. Bone morphogenetic proteins (BMPs) are members of the TGF? superfamily, which act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. Ablation of the BMPR1A receptor in osteoblasts increases bone mass, suggesting that inhibition of BMPR1A signaling may have therapeutic benefit. The aim of this study was to determine the skeletal effects of systemic administration of a soluble BMPR1A fusion protein (mBMPR1A–mFc) in vivo. mBMPR1A–mFc was shown to bind BMP2/4 specifically and with high affinity and prevent downstream signaling. mBMPR1A–mFc treatment of immature and mature mice increased bone mineral density, cortical thickness, trabecular bone volume, thickness and number, and decreased trabecular separation. The increase in bone mass was due to an early increase in osteoblast number and bone formation rate, mediated by a suppression of Dickkopf-1 expression. This was followed by a decrease in osteoclast number and eroded surface, which was associated with a decrease in receptor activator of NF-?B ligand (RANKL) production, an increase in osteoprotegerin expression, and a decrease in serum tartrate-resistant acid phosphatase (TRAP5b) concentration. mBMPR1A treatment also increased bone mass and strength in mice with bone loss due to estrogen deficiency. In conclusion, mBMPR1A–mFc stimulates osteoblastic bone formation and decreases bone resorption, which leads to an increase in bone mass, and offers a promising unique alternative for the treatment of bone-related disorders. PMID:22761317

Baud’huin, Marc; Solban, Nicolas; Cornwall-Brady, Milton; Sako, Dianne; Kawamoto, Yoshimi; Liharska, Katia; Lath, Darren; Bouxsein, Mary L.; Underwood, Kathryn W.; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Seehra, Jasbir; Canalis, Ernesto; Pearsall, R. Scott; Croucher, Peter I.

2012-01-01

288

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

2012-06-01

289

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

290

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

PubMed Central

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

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

2013-01-01

291

[Comparative characterization of mesenchymal bone marrow stromal cells at early and late stages of culturing].  

PubMed

The mesenchymal stromal cell is a multipotent precursor of osteoblasts, adipocytes, and some other cell types. In this study, a comparative analysis of cultured mesenchymal stromal cells from the rat bone marrow at the early and late stages of subculturing has been performed using molecular genetic and cytological methods. The culture has undergone 11 passages during 140 days. Upon long-term culturing, the mesenchymal stromal cells have proved to lose their potential for adipogenic differentiation but preserve the potential for osteogenesis. Morphological characters typical of osteogenic differentiation can be observed at the earlier stages of culturing (passages 1-4) but disappear at later stages (passages 9-11), despite mineralization of the extracellular matrix and the expression of osteogenic differentiation markers. A comparative analysis of the proliferation potential of stromal cells has shown that differences in the period of cell population doubling at the early and later stages of culturing are insignificant. An almost complete arrest of cell growth has been observed in the middle of the culture period (passages 5 and 6). PMID:18946989

Kozhevnikova, M N; Mikaelian, A S; Paiushina, O V; Starostin, V I

2008-01-01

292

Diagnostic role of 99Tcm-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for early and atypical bone metastases  

PubMed Central

The bone metastasis appeared early before the bone imaging for most of the above patients. 99Tcm-MDP (99Tcm marked methylene diphosphonate) bone imaging could diagnosis the bone metastasis with highly sensitivity, but with lower specificity. The aim of this study is to explore the diagnostic value of 99Tcm-MDP SPECT/CT combined SPECT/MRI Multi modality imaging for the early period atypical bone metastases. 15 to 30 mCi 99Tcm-MDP was intravenously injected to the 34 malignant patients diagnosed as doubtful early bone metastases. SPECT, CT and SPECT/CT images were captured and analyzed consequently. For the patients diagnosed as early period atypical bone metastases by SPECT/CT, combining the SPECT/CT and MRI together as the SPECT/MRI integrated image. The obtained SPECT/MRI image was analyzed and compared with the pathogenic results of patients. The results indicated that 34 early period doubtful metastatic focus, including 34 SPECT positive focus, 17 focus without special changes by using CT method, 11 bone metastases focus by using SPECT/CT method, 23 doubtful bone metastases focus, 8 doubtful bone metastases focus, 14 doubtful bone metastases focus and 2 focus without clear image. Totally, SPECT/CT combined with SPECT/MRI method diagnosed 30 bone metastatic focus and 4 doubtfully metastatic focus. In conclusion, 99Tcm-MDP SPECT/CT combined SPECT/MRI Multi modality imaging shows a higher diagnostic value for the early period bone metastases, which also enhances the diagnostic accuracy rate.

Chen, Xiao-Liang; Li, Qian; Cao, Lin; Jiang, Shi-Xi

2014-01-01

293

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

PubMed

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

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

2012-04-01

294

The effects of expectancy violations on early attention to race in an impression-formation paradigm  

Microsoft Academic Search

Previous research has demonstrated that early attentional components of the event-related potential (ERP) reflect differential attention to race during person perception. There is also evidence that inconsistency between stereotypic information following impression formation leads to greater neural processing in later ERP components. However, research has not examined how expectancy violations following impression formation affect the early attentional processing of race.

Cheryl Dickter; Ivo Gyurovski

2011-01-01

295

The effects of expectancy violations on early attention to race in an impression-formation paradigm  

Microsoft Academic Search

Previous research has demonstrated that early attentional components of the event-related potential (ERP) reflect differential attention to race during person perception. There is also evidence that inconsistency between stereotypic information following impression formation leads to greater neural processing in later ERP components. However, research has not examined how expectancy violations following impression formation affect the early attentional processing of race.

Cheryl Dickter; Ivo Gyurovski

2012-01-01

296

Combination of BMP2 and MSCs Significantly Increases Bone Formation in the Rat Arterio-Venous Loop Model.  

PubMed

Introduction: In this study the induction of bone formation in an axially vascularized bone matrix using mesenchymal stem cells (MSCs) and application of bone morphogenetic protein 2 (BMP2) was analyzed in the arteriovenous loop (AVL) model. Materials and Methods: An AVL was created in the medial thigh of 42 rats and placed in a porous titanium chamber filled with a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix and fibrin. In group A the fibrin was loaded with 5×10(6) DiI-stained fibrin gel-immobilized primary MSCs from syngenic Lewis rats, in group B the matrix was loaded with 60??g/mL BMP2 and in group C both, BMP2 and MSCs were applied at implantation time point. After 6 and 12 weeks, specimens were investigated by means of histological, morphometrical, and micro-computed tomography analysis. Results: After implantation of an AVL a dense vascular network was visible in all groups. In group A, newly generated bone islands were detected in the periphery of the main vascular axis. Using BMP2 alone (group B), small islands of newly formed bone were visible evenly distributed in all parts of the constructs. In group C nearly the whole matrix was interspersed with bone formations. In all groups there was an increase of bone formation between the 6 and 12 weeks explantation time points. Conclusions: This study demonstrates for the first time the successful generation of axially vascularized bone substitutes using MSCs and BMP2 in the AVL rat model using a one step procedure. Using the combination of BMP2 and MSCs there was a significant increase of bone formations detectable compared to the BMP2 or MSCs alone groups. PMID:25135080

Buehrer, Gregor; Balzer, Amelie; Arnold, Isabel; Beier, Justus P; Koerner, Carolin; Bleiziffer, Oliver; Brandl, Andreas; Weis, Christian; Horch, Raymund E; Kneser, Ulrich; Arkudas, Andreas

2014-11-01

297

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. PMID:21347550

Lü, Kaige; Zeng, Dengliang; Zhang, Yilin; Xia, Lunguo; Xu, Ling; Kaplan, David L.; Jiang, Xinquan; Zhang, Fuqiang

2012-01-01

298

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

299

Effect of Different rhBMP-2 and TG-VEGF Ratios on the Formation of Heterotopic Bone and Neovessels  

PubMed Central

Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles. PMID:24783213

Cai, Wei Xin; Li, Chun Lei; Ehrbar, Martin; Weber, Franz E.; Zwahlen, Roger A.

2014-01-01

300

Effect of different rhBMP-2 and TG-VEGF ratios on the formation of heterotopic bone and neovessels.  

PubMed

Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles. PMID:24783213

Cai, Wei Xin; Zheng, Li Wu; Li, Chun Lei; Ma, Li; Ehrbar, Martin; Weber, Franz E; Zwahlen, Roger A

2014-01-01

301

Formation of the early atmosphere from late-accreting planetesimals Sujoy Mukhopadhyay*  

E-print Network

1 Formation of the early atmosphere from late-accreting planetesimals Sujoy Mukhopadhyay* , Rita, Cambridge MA 02138, USA. * Corresponding author Abstract The composition of Earth's early atmosphere strongly influenced chemical reactions on our planet's surface. For example, an early reducing atmosphere

Mukhopadhyay, Sujoy

302

A perfusion bioreactor system capable of producing clinically relevant volumes of tissue-engineered bone: in vivo bone formation showing proof of concept.  

PubMed

In an effort to produce clinically relevant volumes of tissue-engineered bone products, we report a direct perfusion bioreactor system. Goat bone marrow stromal cells (GBMSCs) were dynamically seeded and proliferated in this system in relevant volumes (10 cc) of small sized macroporous biphasic calcium phosphate scaffolds (BCP, 2-6 mm). Cell load and cell distribution were shown using methylene blue block staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining was used to demonstrate viability of the present cells. After 19 days of cultivation, the scaffolds were covered with a viable, homogeneous cell layer. The hybrid structures became interconnected and a dense layer of extracellular matrix was present as visualized by environmental scanning electron microscopy (ESEM). ESEM images showed within the extracellular matrix sphere like structures which were identified as calcium phosphate nodules by energy dispersive X-ray analysis (EDX). On line oxygen measurements during cultivation were correlated with proliferating GBMSCs. It was shown that the oxygen consumption can be used to estimate GBMSC population doubling times during growth in this bioreactor system. Implantation of hybrid constructs, which were proliferated dynamically, showed bone formation in nude mice after 6 weeks of implantation. On the basis of our results we conclude that a direct perfusion bioreactor system is capable of producing clinically relevant volumes of tissue-engineered bone in a bioreactor system which can be monitored on line during cultivation and show bone formation after implantation in nude mice. PMID:16125223

Janssen, Frank W; Oostra, Jaap; Oorschot, Arie van; van Blitterswijk, Clemens A

2006-01-01

303

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

PubMed Central

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

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

2015-01-01

304

Interaction between nandrolone decanoate and calcitonin in bone formation markers (osteocalcin and bone specific alkaline phosphatase) and IGF-I in rats.  

PubMed

Bone tissue has been shown to contain numerous cell-to-cell signaling peptides called growth factors. These growth factors are thought to have important regulating effects for bone remodeling, due to their potent effects on bone cell metabolism. Our investigation was intended to assess the effect of nandrolone decanoate and calcitonin treatment on biochemical markers of bone formation (bone alkaline phosphatase - osteocalcin) and insulin-like growth factor-I in rats. We studied 48 adult male rats. The animals were divided into four groups. Group (A) served as control. Animals in Group (B) were injected with 4 mg/kg/day nandrolone decanoate. Animals in Group (C) were injected with 400mU/rat/day calcitonin and Group (D) received combined therapy for seven days. Nandrolone decanoate and calcitonin have a mild but significant effect on insulin-like growth factor-I without affecting osteocalcin levels, while calcitonin alone decreases the BALP levels. The coadministration of two agents caused notable elevation on insulin-like growth factor-I, followed by a significant increase of osteocalcin and bone alkaline phosphatase. PMID:15758466

Saranteas, T; Mourouzis, C; Mezitis, M; Tesseromatis, C; Spyraki, C

2001-12-01

305

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases  

Microsoft Academic Search

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28

J L Mansi; U Berger; D Easton; T McDonnell; W H Redding; J C Gazet; A McKinna; T J Powles; R C Coombes

1987-01-01

306

Growth From Birth to Adulthood and Bone Phenotype in Early Old Age: A British Birth Cohort Study  

PubMed Central

There is growing evidence that early growth influences bone mass in later life but most studies are limited to birth weight and/or early infant growth and dual-energy X-ray absorptiometry (DXA) measurements. In a British birth cohort study with prospective measures of lifetime height and weight, we investigated the growth trajectory in relation to bone in males (M) and females (F) at 60 to 64 years old. Outcomes were DXA measures of hip and spine areal bone density (aBMD) (n = 1658) and pQCT measures of distal and diaphyseal radius cross-sectional area (CSA), strength, and volumetric bone density (vBMD) (n = 1350 of the 1658). Regression models examined percentage change in bone parameters with standardized measures of birth weight, height, and weight. A series of conditional growth models were fitted for height and weight gain (using intervals: birth–2, 2–4, 4–7, 7–15, 15–20, 20–36, and 36–64 years) and height gain (using intervals: 2–4, 4–7, 7–15, and 15–36 years). Birth weight was positively related to bone CSA (M: 1.4%; 95% confidence interval [CI], 0.3%–2.5%; F: 1.3%; 95% CI, 0.3%–2.4% per 1 SD increase in birth weight for diaphyseal CSA) and strength (M: 1.8%; 95% CI, 0.3–3.4; F: 2.0%; 95% CI, 0.5–3.5). No positive associations were found with trabecular, total, or cortical vBMD. One SD change in prepubertal and postpubertal height and weight velocities were associated with between 2% and 5% greater bone CSA and strength. Height gain in later years was negatively associated with trabecular vBMD. Weight gain velocity during the adult years was positively associated with up to 4% greater trabecular and total BMD, and 4% greater aBMD at hip and spine. In a cohort born in the early post-war period, higher birth weight, gaining weight and height faster than others, particularly through the prepubertal and postpubertal periods, was positively related to bone strength, mostly through greater bone CSA, at 60 to 64 years. PMID:23761289

Kuh, Diana; Wills, Andrew K; Shah, Imran; Prentice, Ann; Hardy, Rebecca; Adams, Judith E; Ward, Kate; Cooper, Cyrus

2014-01-01

307

Stimulation of Chondrocyte Hypertrophy by Chemokine Stromal Cell-Derived Factor 1 in the Chondro-osseous Junction during Endochondral Bone Formation  

PubMed Central

During endochondral bone formation, chondrocytes undergo differentiation toward hypertrophy before they are replaced by bone and bone marrow. In this study, we found that a G-protein coupled receptor CXCR4 is predominantly expressed in hypertrophic chondrocytes, while its ligand, chemokine stromal cell derived factor 1 (SDF-1) is expressed in the bone marrow adjacent to hypertrophic chondrocytes. Thus, they are expressed in a complementary pattern in the chondro-osseous junction of the growth plate. Transfection of a CXCR4 cDNA into pre-hypertrophic chondrocytes results in a dose-dependent increase of hypertrophic markers including Runx2, Col X, and MMP-13 in response to SDF-1 treatment. In organ culture SDF-1 infiltrates cartilage and accelerates growth plate hypertrophy. Furthermore, a continuous infusion SDF-1 into the rabbit proximal tibial physis results in early physeal closure, which is accompanied by a transient elevation of type X collagen expression. Blocking SDF-1/CXCR4 interaction suppresses the expression of Runx2. Thus, interaction of SDF-1 and CXCR4 is required for Runx2 expression. Interestingly, knocking down Runx2 gene expression results in a decrease of CXCR4 mRNA levels in hypertrophic chondrocytes. This suggests a positive feedback loop of stimulation of chondrocyte hypertrophy by SDF-1/CXCR4, which is mediated by Runx2. PMID:20206617

Wei, Lei; Kanbe, Katsuaki; Lee, Mark; Wei, Xiaochun; Pei, Ming; Sun, Xiaojuan; Terek, Richard; Chen, Qian

2010-01-01

308

Hypoxia Modulates the Phenotype of Osteoblasts Isolated From Knee Osteoarthritis Patients, Leading to Undermineralized Bone Nodule Formation  

PubMed Central

Objective To investigate the role of hypoxia in the pathology of osteoarthritic (OA) bone by exploring its effect on the phenotype of isolated primary osteoblasts from patients with knee OA. Methods OA bone samples were collected at the time of elective joint replacement surgery for knee or hip OA. Normal bone samples were collected postmortem from cadaver donors. Primary osteoblasts were isolated from knee OA bone chips and cultured under normoxic or hypoxic (2% O2) conditions. Alkaline phosphatase activity was quantified using an enzymatic assay, and osteopontin and prostaglandin E2 (PGE2) production was assayed by enzyme-linked immunosorbent assay. Total RNA was extracted from bone and osteoblasts, and gene expression was profiled by quantitative reverse transcription–polymerase chain reaction. Results Human OA bone tissue sections stained positively for carbonic anhydrase IX, a biomarker of hypoxia, and exhibited differential expression of genes that mediate the vasculature and blood coagulation as compared to those found in normal bone. Culture of primary osteoblasts isolated from knee OA bone under hypoxic conditions profoundly affected the osteoblast phenotype, including the expression of genes that mediate bone matrix, bone remodeling, and bone vasculature. Hypoxia also increased the expression of cyclooxygenase 2 and the production of PGE2 by OA osteoblasts. Osteoblast expression of type II collagen ?1 chain, angiopoietin-like 4, and insulin-like growth factor binding protein 1 was shown to be mediated by hypoxia-inducible factor 1?. Chronic hypoxia reduced osteoblast- mineralized bone nodule formation. Conclusion These findings demonstrate that hypoxia can induce pathologic changes in osteoblast functionality consistent with an OA phenotype, providing evidence that hypoxia is a key driver of OA pathology. PMID:24574272

Chang, Joan; Jackson, Sonya G; Wardale, John; Jones, Simon W

2014-01-01

309

Risedronate preserves bone architecture in early postmenopausal women in 1 year as measured by three-dimensional microcomputed tomography.  

PubMed

Risedronate reduces the risk of vertebral fractures by up to 70% within the first year of treatment. Increases in bone mineral density or decreases in bone turnover markers explain only a portion of the anti-fracture effect, suggesting that other factors, such as changes in trabecular bone architecture, also play a role. Our objective was to determine the effects of risedronate on bone architecture by analyzing iliac crest bone biopsy specimens using three-dimensional microcomputed tomography (3-D micro CT). Biopsy specimens were obtained at baseline and after 1 year of treatment from women enrolled in a double-blind, placebo-controlled study of risedronate 5 mg daily for the prevention of early postmenopausal bone loss. Trabecular architecture deteriorated in the placebo group (n = 12), as indicated by a 20.3% decrease in bone volume (25.1% vs. 20.0%, P = 0.034), a 13.5% decrease in trabecular number (1.649 vs. 1.426 mm(-1), P = 0.052), a 13.1% increase in trabecular separation (605 vs. 684 microm, P = 0.056), and an 86.2% increase in marrow star volume (3.251 vs. 6.053 mm(3), P = 0.040) compared with baseline values. These changes in architectural parameters occurred in the presence of a concomitant decrease from baseline in lumbar spine bone mineral density (-3.3%, P = 0.002), as measured by dual energy x-ray absorptiometry. There was no statistically significant ( P < 0.05) deterioration in the risedronate-treated group (n = 14) over the 1-year treatment period. Comparing the actual changes between the two groups, the placebo group experienced decreases in bone volume (placebo, -5.1%; risedronate, +3.5%; P = 0.011), trabecular thickness (placebo, -20 microm; risedronate, +23 microm; P = 0.032), and trabecular number (placebo, -0.223 mm(-1); risedronate, +0.099 mm(-1); P = 0.010), and increases in percent plate (placebo, +2.79%; risedronate, -3.23%; P = 0.018), trabecular separation (placebo, +79 microm; risedronate, -46 microm; P = 0.010) and marrow star volume (placebo, +2.80 mm(3); risedronate, -2.08mm(3); P = 0.036), compared with the risedronate group. These data demonstrate that trabecular architecture deteriorated significantly in this cohort of early postmenopausal women, and that this deterioration was prevented by risedronate. Although there is no direct link in this study between fracture and preservation of architecture, it is reasonable to infer that the preservation of bone architecture may play a role in risedronate's anti-fracture efficacy. PMID:12964065

Dufresne, T E; Chmielewski, P A; Manhart, M D; Johnson, T D; Borah, B

2003-11-01

310

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

311

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

PubMed Central

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

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

2013-01-01

312

Heat and radiofrequency plasma glow discharge pretreatment of a titanium alloy promote bone formation and osseointegration.  

PubMed

Orthopedic and dental implants manifest increased failure rates when inserted into low density bone. We determined whether chemical pretreatments of a titanium alloy implant material stimulated new bone formation to increase osseointegration in vivo in trabecular bone using a rat model. Titanium alloy rods were untreated or pretreated with heat (600°C) or radiofrequency plasma glow discharge (RFGD). The rods were then coated with the extracellular matrix protein fibronectin (1 nM) or left uncoated and surgically implanted into the rat femoral medullary cavity. Animals were euthanized 3 or 6 weeks later, and femurs were removed for analysis. The number of trabeculae in contact with the implant surface, surface contact between trabeculae and the implant, and the length and area of bone attached to the implant were measured by histomorphometry. Implant shear strength was measured by a pull-out test. Both pretreatments and fibronectin enhanced the number of trabeculae bonding with the implant and trabeculae-to-implant surface contact, with greater effects of fibronectin observed with pretreated compared to untreated implants. RFGD pretreatment modestly increased implant shear strength, which was highly correlated (r(2) = 0.87-0.99) with measures of trabecular bonding for untreated and RFGD-pretreated implants. In contrast, heat pretreatment increased shear strength 3-5-fold for both uncoated and fibronectin-coated implants at 3 and 6 weeks, suggesting a more rapid increase in implant-femur bonding compared to the other groups. In summary, our findings suggest that the heat and RFGD pretreatments can promote the osseointegration of a titanium alloy implant material. PMID:23649564

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

2013-10-01

313

The optimum zinc content in set calcium phosphate cement for promoting bone formation in vivo  

PubMed Central

The final aim of our study is to develop a novel calcium phosphate cement based on zinc-containing ?-tricalcium phosphate (?ZnTCP) and evaluate its potential as bonegraft material in vivo. In the present study, in vivo efficacy of zinc in hardened bodies of ?ZnTCP was explored. The hardened bodies prepared from ?ZnTCP with zinc content of 0.00, 0.04, 0.08, 0.11 and 0.19 wt % were prepared by mixing pure ?TCP or ?ZnTCP powder with 12 wt% sodium succinate solution at a solid-to-liquid ratio of 2.0. Due to the release of zinc ions into the physiological salt solution during curing, the zinc content in the hardened bodies was calculated to be 0.00, 0.03, 0.06, 0.10 and 0.18 wt%, respectively. The hardened bodies were implanted in the femora and tibia of white rabbits for 4 weeks. Histological and histomorphometric evaluation showed that the hardened body containing 0.03 wt% zinc, significantly promoted more new bone formation without evoking adverse tissue reactions than that without zinc. The hardened bodies containing 0.06 and 0.10 wt% zinc also resulted in the increase in numbers of active osteoblasts surrounding the new bone but caused inflammation at the implant sites. Results of this study indicate that the hardened body prepared with ?ZnTCP is superior to that prepared with ?TCP in promoting new bone formation due to the release of zinc ions. This study also indicates that the optimum amount of zinc in the hardened body is about 0.03 wt % to avoid inflammatory reaction. PMID:21461346

Li, Xia; Sogo, Yu; Ito, Atsuo; Mutsuzaki, Hirotaka; Ochiai, Naoyuki; Kobayashi, Takayuki; Nakamura, Satoshi; Yamashita, Kimihiro; LeGeros, Racquel Z.

2009-01-01

314

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

315

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

316

Mesenchymal Stem Cells in Early Entry of Breast Cancer into Bone Marrow  

PubMed Central

Background An understanding of BC cell (BCC) entry into bone marrow (BM) at low tumor burden is limited when compared to highly metastatic events during heavy tumor burden. BCCs can achieve quiescence, without interfering with hematopoiesis. This occurs partly through the generation of gap junctions with BM stroma, located close to the endosteum. These events are partly mediated by the evolutionary conserved gene, Tac1. Methodogy/Principal Findings This study focuses on the role of mesenchymal stem cells (MSCs), Tac1, SDF-1 and CXCR4 in BCC entry into BM. The model is established in studies with low numbers of tumor cells, and focuses on cancer cells with low metastatic and invasion potential. This allowed us to recapitulate early event, and to study cancer cells with low invasive potential, even when they are part of larger numbers of highly metastatic cells. A novel migration assay showed a facilitating role of MSCs in BCC migration across BM endothelial cells. siRNA and ectopic expression studies showed a central role for Tac1 and secondary roles for SDF-1? and CXCR4. We also observed differences in the mechanisms between low invasive and highly metastatic cells. The in vitro studies were verified in xenogeneic mouse models that showed a preference for low invasive BCCs to BM, but comparable movement to lung and BM by highly metastatic BCCs. The expressions of Tac1 and production of SDF-1? were verified in primary BCCs from paired samples of BM aspirates and peripheral blood. Conclusions/Significance MSC facilitate BCC entry into BM, partly through Tac1-mediated regulation of SDF-1? and CXCR4. We propose a particular population of BCC with preference for BM could be isolated for characterization. This population might be the subset that enter BM at an early time period, and could be responsible for cancer resurgence and resistance to current therapies. PMID:18575622

Corcoran, Kelly E.; Trzaska, Katarzyna A.; Fernandes, Helen; Bryan, Margarette; Taborga, Marcelo; Srinivas, Venkatesh; Packman, Kathryn; Patel, Prem S.; Rameshwar, Pranela

2008-01-01

317

Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils.  

PubMed

Expansion of myeloid cells associated with solid tumor development is a key contributor to neoplastic progression. Despite their clinical relevance, the mechanisms controlling myeloid cell production and activity in cancer remains poorly understood. Using a multistage mouse model of breast cancer, we show that production of atypical T cell-suppressive neutrophils occurs during early tumor progression, at the onset of malignant conversion, and that these cells preferentially accumulate in peripheral tissues but not in the primary tumor. Production of these cells results from activation of a myeloid differentiation program in bone marrow (BM) by a novel mechanism in which tumor-derived granulocyte-colony stimulating factor (G-CSF) directs expansion and differentiation of hematopoietic stem cells to skew hematopoiesis toward the myeloid lineage. Chronic skewing of myeloid production occurred in parallel to a decrease in erythropoiesis in BM in mice with progressive disease. Significantly, we reveal that prolonged G-CSF stimulation is both necessary and sufficient for the distinguishing characteristics of tumor-induced immunosuppressive neutrophils. These results demonstrate that prolonged G-CSF may be responsible for both the development and activity of immunosuppressive neutrophils in cancer. PMID:25624500

Casbon, Amy-Jo; Reynaud, Damien; Park, Chanhyuk; Khuc, Emily; Gan, Dennis D; Schepers, Koen; Passegué, Emmanuelle; Werb, Zena

2015-02-10

318

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

PubMed Central

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

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

2014-01-01

319

Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study  

PubMed Central

Introduction Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference. Methods In a stepwise approach different PET tracers were investigated. First, whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [18F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data. Results No increased [18F]FDG and [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT, [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an uptake of five times lower compared to [18F]Fluoride, and again no [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [18F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [18F]Fluoride PET positive lesions. Conclusions Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [18F]Fluoride. In contrast to active RA, inflammation tracers [18F]FDG and [11C](R)PK11195 appeared to be less useful for AS imaging. PMID:22471910

2012-01-01

320

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

PubMed Central

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

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

2014-01-01

321

Bone Metabolism on ISS Missions  

NASA Technical Reports Server (NTRS)

Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those that existed before space flight. Studies to assess bone strength after flight are underway at NASA, to better understand the results of bone remodeling. Studies are also underway to evaluate optimized exercise protocols and nutritional countermeasures. Regardless, there is clear evidence of progress being made to protect bone during spaceflight.

Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

2014-01-01

322

Bone mineral density and body composition before and during treatment with gonadotropin-releasing hormone agonist in children with central precocious and early puberty  

Microsoft Academic Search

Major changes in bone mineral density (BMD) and body composition occur\\u000a during puberty. In the present longitudinal study, we evaluated BMD and\\u000a calculated volumetric BMD [bone mineral apparent density (BMAD)], bone\\u000a metabolism, and body composition of children (32 girls and 2 boys) with\\u000a central precocious and early puberty before and during treatment with GnRH\\u000a agonist (GnRH). Patients were studied at

A. M. Boot; Muinck Keizer-Schrama de S. M. P. F; H. A. P. Pols; E. P. Krenning; S. L. S. Drop

1998-01-01

323

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

NASA Astrophysics Data System (ADS)

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

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

2007-05-01

324

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

PubMed

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

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

2012-09-01

325

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

PubMed Central

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

Sugiyama, Toshie; Kusuhara, Seiji; Uchida, Takashi

2012-01-01

326

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

PubMed

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

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

2014-08-01

327

Staphylococcal biofilm formation on the surface of three different calcium phosphate bone grafts: a qualitative and quantitative in vivo analysis.  

PubMed

Differences in physico-chemical characteristics of bone grafts to fill bone defects have been demonstrated to influence in vitro bacterial biofilm formation. Aim of the study was to investigate in vivo staphylococcal biofilm formation on different calcium phosphate bone substitutes. A foreign-body guinea-pig infection model was used. Teflon cages prefilled with ?-tricalcium phosphate, calcium-deficient hydroxyapatite, or dicalcium phosphate (DCP) scaffold were implanted subcutaneously. Scaffolds were infected with 2 × 10(3) colony-forming unit of Staphylococcus aureus (two strains) or S. epidermidis and explanted after 3, 24 or 72 h of biofilm formation. Quantitative and qualitative biofilm analysis was performed by sonication followed by viable counts, and microcalorimetry, respectively. Independently of the material, S. aureus formed increasing amounts of biofilm on the surface of all scaffolds over time as determined by both methods. For S. epidermidis, the biofilm amount decreased over time, and no biofilm was detected by microcalorimetry on the DCP scaffolds after 72 h of infection. However, when using a higher S. epidermidis inoculum, increasing amounts of biofilm were formed on all scaffolds as determined by microcalorimetry. No significant variation in staphylococcal in vivo biofilm formation was observed between the different materials tested. This study highlights the importance of in vivo studies, in addition to in vitro studies, when investigating biofilm formation of bone grafts. PMID:25693675

Furustrand Tafin, Ulrika; Betrisey, Bertrand; Bohner, Marc; Ilchmann, Thomas; Trampuz, Andrej; Clauss, Martin

2015-03-01

328

Star formation histories in early-type galaxies  

E-print Network

I discuss the formation of alpha-enhanced metal-rich stellar populations in the nuclei of luminous ellipticals. Based on hierarchical clustering, different galaxy formation scenarios, which imply different star formation histories, are considered. In contrast to the fast clumpy collapse mode, the late merger of two spiral galaxies fails to reproduce significantly $\\alpha$-enhanced abundance ratios, unless the IMF is flattened. Following the star formation history predicted by semi-analytic models of hierarchical clustering for the average elliptical, solar abundance ratios are obtained with Salpeter IMF. According to the models, bright ellipticals in the field are expected to have significantly lower Mg/Fe ratios than their counterparts in a cluster.

D. Thomas

1998-08-24

329

New information on olenelline trilobites from the Early Cambrian Sekwi Formation, Northwestern Canada  

E-print Network

A new species of olenelline trilobite, Nevadella keelensis, is described from the Early Cambrian (Cambrian Series 2, Stage 3) in the Sekwi Formation, Mackenzie Mountains, Canada. The difficulty in discerning between Nevadia Walcott, 1910...

Abe, Francine Reiko; Lieberman, Bruce S.; Pope, Michael C.; Dilliard, Kelly A.

2010-08-16

330

Diabetes interferes with the bone formation by affecting the expression of transcription factors that regulate osteoblast differentiation.  

PubMed

Type 1 diabetes in humans has as one of its complications inadequate bone formation, resulting in osteopenia and delayed fracture healing. To investigate the mechanisms by which diabetes affects bone formation, experiments were performed 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, 2, 4, 6, 10, and 16 d following marrow ablation. Histologic analysis demonstrated that the amount of immature mesenchymal tissue was equivalent in both the experimental and control groups on d 4. On d 6 a burst of bone formation occurred in the control group that was significantly reduced in the diabetic group. This deficit was evident at the molecular level as shown by diminished expression of osteocalcin, collagen types I. When transcription factors were examined, core-binding factor alpha1 (Cbfa1)/runt domain factor-2 (Runx-2) and human homolog of the drosophila distal-less gene (Dlx5) expression were substantially reduced in the diabetic, compared with control, groups on d 4 and 6. C-fos but not c-jun expression was also suppressed in the diabetic group but not closely linked to bone formation. Insulin treatment substantially reversed the effect of diabetes on the expression of bone matrix osteocalcin and collagen type I and transcription factors Cbfa1/Runx2 and Dlx5. These results indicate that diabetic animals produce sufficient amounts of immature mesenchymal tissue but fail to adequately express genes that regulate osteoblast differentiation, Cbfa1/Runx-2 and Dlx5, which in turn, leads to decreased bone formation. PMID:12488363

Lu, Huafei; Kraut, Douglas; Gerstenfeld, Louis C; Graves, Dana T

2003-01-01

331

Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.  

PubMed

The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats. PMID:9528976

Oxlund, H; Andersen, N B; Ortoft, G; Orskov, H; Andreassen, T T

1998-04-01

332

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

PubMed

Synthetic calcium hydroxyapatite (HAP,Ca(10)(PO(4))(6)(OH)(2)) is a well-known bioceramic material used in orthopaedic and dental applications because of its excellent biocompatibility and bone-bonding ability. Substitution of trace elements, such as Sr, Mg and Zn ions into the structure of calcium phosphates is the subject of widespread investigation. In this paper, we have reported the synthesis of Sr, Mg and Zn co-substituted nanohydroxyapatite by soft solution freezing method. The effect of pH on the morphology of bioceramic nanomaterial was also discussed. The in vitro bioactivity of the as-synthesized bioceramic nanomaterial was determined by soaking it in SBF for various days. The as-synthesized bioceramic nanomaterial was characterized by Fourier transform infrared spectroscopy, X- ray diffraction analysis, Scanning electron microscopy and Energy dispersive X-ray analysis and Transmission electron microscopic techniques respectively. The results obtained in our study have revealed that pH 10 was identified to induce the formation of mineralized nanohydroxyapatite. It is observed that the synthesis of bioceramic nanomaterial not only support the growth of apatite layer on its surface but also accelerate the growth which is evident from the in vitro studies. Therefore, mineralized nanohydroxyapatite is a potential candidate in bone tissue engineering. PMID:22446767

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

2012-06-15

333

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

NASA Astrophysics Data System (ADS)

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

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

334

Anabolic Bone Formation Via a Site Specific Bone Targeting Delivery System by Interfering with Semaphorin 4D Expression.  

PubMed

Recently semaphorins have been targeted as new molecules directly implicated in the cell-cell communication that occurs between osteoclasts and osteoblasts. Over-expression of certain semaphorins such as semaphorin4D (sema4D) is found in an osteoporotic phenotype and plays a key role in osteoclast activity by suppressing osteoblast maturation, thus significantly altering the bone modelling cycle. In the present study, we fabricate a site-specific bone-targeting drug delivery system from polymeric nanoparticles with the incorporation of siRNA interference molecule for sema4D and demonstrate their cellular uptake and intracellular trafficking within osteoclasts, thus preventing the suppression of osteoblast activity. We then demonstrate in an osteoporotic animal model induced by ovariectomy that weekly intravenous injections led to a significantly greater number of active osteoblasts at the bone surface resulting in higher bone volume in compromised animals. The findings from the present study demonstrate a novel and promising site-specific therapeutic option for the treatment of osteoporosis via interference of the sema4D-plexin cell communication pathway between osteoclasts and osteoblasts. © 2014 American Society for Bone and Mineral Research. PMID:25088728

Zhang, Yufeng; Wei, Lingfei; Miron, Richard J; Shi, Bin; Bian, Zhuan

2014-08-01

335

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

SciTech Connect

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

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

2012-05-01

336

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

NASA Astrophysics Data System (ADS)

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

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

2014-03-01

337

Platelet lysate coating on scaffolds directly and indirectly enhances cell migration, improving bone and blood vessel formation.  

PubMed

Suitable colonization and vascularization of tissue-engineered constructs after transplantation represent critical steps for the success of bone repair. Human platelet lysate (hPL) is composed of numerous growth factors known for their proliferative, differentiative and chemo-attractant effects on various cells involved in wound healing and bone growth. The aim of this study was to determine whether the delivery of human mesenchymal stromal cells (hMSC) seeded on hPL-coated hydroxyapatite/?-tricalcium phosphate (HA/?-TCP) scaffolds could enhance vascularization and bone formation, as well as to investigate the mechanisms by which hMSC participate in tissue regeneration. Our study demonstrates that hPL can be coated on HA/?-TCP scaffolds, which play direct and indirect effects on implanted and/or resident stem cells. Effectively, we show that hPL coating directly increases chemo-attraction to and adhesion of hMSC and endothelial cells on the scaffold. Moreover, we show that hPL coating induces hMSC to produce and secrete pro-angiogenic proteins (placental growth factor and vascular endothelial growth factor) which allow the proliferation and specific chemo-attraction of endothelial cells in vitro, thus improving in vivo neovascularization and new bone formation. This study highlights the potential of functionalizing biomaterials with hPL and shows that this growth factor combination can have synergistic effects leading to enhanced bone and blood vessel formation. PMID:23403167

Leotot, Julie; Coquelin, Laura; Bodivit, Gwellaouen; Bierling, Philippe; Hernigou, Philippe; Rouard, Helene; Chevallier, Nathalie

2013-05-01

338

Early Oligocene initiation of North Atlantic Deep Water formation  

Microsoft Academic Search

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

Richard Davies; Joseph Cartwright; Jennifer Pike; Charles Line

2001-01-01

339

Martian dichotomy formation by partial melting coupled to early  

E-print Network

13, 2011 #12;Endogenic origin?? Sleep 1994 early episode of plate tectonics on Mars 14Wednesday at Dept. of Geophysics, Charles Univ. in Prague 1Wednesday, April 13, 2011 #12;Mars · radius 3400 km that of the Earth) 2Wednesday, April 13, 2011 #12;Mars Global Surveyor (MGS) mission 1996­2006 · Mars Orbiter Camera

Cerveny, Vlastislav

340

Early microbial biofilm formation on marine plastic debris  

Microsoft Academic Search

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

Delphine Lobelle; Michael Cunliffe

2011-01-01

341

Inhibitory effects of osteoblasts and increased bone formation on myeloma in novel culture systems and a myelomatous mouse model  

PubMed Central

Background and Objectives Multiple myeloma (MM) growth in the bone marrow is associated with increased osteoclast activity and a reduced number of osteoblasts. Experimental studies suggest that bone disease drives the progression of MM. Whereas those studies focused on the critical role of myeloma-induced osteoclastogenesis in disease progression, little is known about the impact of osteoblasts and increased bone formation on MM. Design and Methods We investigated the effect of isolated osteoblasts and osteoclasts on survival and proliferation of primary MM plasma cells (PC) in co-cultures and triple-cultures, and tested the effect of mesenchymal stem cells (MSC) on bone mineral density and MM growth in myelomatous human bones of SCID-hu mice. Results Whereas osteoclasts promoted survival and proliferation of MM PC, osteoblasts supported or inhibited MM PC, depending on the source of the MM cells. In triple-cultures osteoblasts attenuated the effect of osteoclasts on MM PC in 18 of 24 experiments. The anti-MM response to osteoblasts correlated with advanced clinical stage. Injection of MSC into myelomatous bones resulted in marked inhibition of tumor growth in three of nine experiments and stabilization of disease in two additional experiments. The anti-MM response of MSC was associated with increased human bone mineral density. Immunohistochemical analysis indicated that the MSC were well engrafted and, in responding mice, differentiated into osteogenic cells. Interpretation and Conclusions MM PC from the majority of patients are susceptible to growth inhibition by osteoblasts; however, growth of MM PC from certain patients is accelerated by osteoblasts. In vivo, increased bone formation is associated with reduced myeloma burden. PMID:16461303

Yaccoby, Shmuel; Wezeman, Michele J.; Zangari, Maurizio; Walker, Ronald; Cottler-Fox, Michele; Gaddy, Danna; Ling, Wen; Saha, Rinku; Barlogie, Bart; Tricot, Guido; Epstein, Joshua

2006-01-01

342

Vitamin D deficiency induces early signs of aging in human bone, increasing the risk of fracture.  

PubMed

Vitamin D deficiency is a widespread medical condition that plays a major role in human bone health. Fracture susceptibility in the context of low vitamin D has been primarily associated with defective mineralization of collagenous matrix (osteoid). However, bone's fracture resistance is due to toughening mechanisms at various hierarchical levels ranging from the nano- to the microstructure. Thus, we hypothesize that the increase in fracture risk with vitamin D deficiency may be triggered by numerous pathological changes and may not solely derive from the absence of mineralized bone. We found that the characteristic increase in osteoid-covered surfaces in vitamin D-deficient bone hampers remodeling of the remaining mineralized bone tissue. Using spatially resolved synchrotron bone mineral density distribution analyses and spectroscopic techniques, we observed that the bone tissue within the osteoid frame has a higher mineral content with mature collagen and mineral constituents, which are characteristic of aged tissue. In situ fracture mechanics measurements and synchrotron radiation micro-computed tomography of the crack path indicated that vitamin D deficiency increases both the initiation and propagation of cracks by 22 to 31%. Thus, vitamin D deficiency is not simply associated with diminished bone mass. Our analyses reveal the aged nature of the remaining mineralized bone and its greatly decreased fracture resistance. Through a combination of characterization techniques spanning multiple size scales, our study expands the current clinical understanding of the pathophysiology of vitamin D deficiency and helps explain why well-balanced vitamin D levels are essential to maintain bone's structural integrity. PMID:23843449

Busse, Björn; Bale, Hrishikesh A; Zimmermann, Elizabeth A; Panganiban, Brian; Barth, Holly D; Carriero, Alessandra; Vettorazzi, Eik; Zustin, Josef; Hahn, Michael; Ager, Joel W; Püschel, Klaus; Amling, Michael; Ritchie, Robert O

2013-07-10

343

CO2-SO2 clathrate hydrate formation on early Mars1 Eric Chassefirea,b  

E-print Network

formation is an observational fact for the current atmosphere of Earth. On early Mars, the60 cooling effect of sulfate aerosols would also have counteracted efficiently the warming effect61 due to SO2 greenhouse atmosphere was necessary in order to keep28 early Mars warm and wet. However, current models have not been

Boyer, Edmond

344

The Early Years: Lyman Spitzer, Jr. and the Physics of Star Formation  

Microsoft Academic Search

The discovery of the interstellar medium and the early work of Lyman Spitzer, Jr. are reviewed here in the context of the remarkable observation in the early 1950's that star formation continues in the present age. Prior to this observation, stars were thought to have formed only at the beginning of the universe. The main debate in the 1930's was

Bruce G. Elmegreen

2009-01-01

345

MRI evaluation of tibial tunnel wall cortical bone formation after platelet-rich plasma applied during anterior cruciate ligament reconstruction  

PubMed Central

Background After anterior cruciate ligament (ACL) reconstruction, formation of cortical sclerotic bone encircling the femoral and tibial tunnel is a part of intratunnel graft healing. During the physiological cascades of soft tissue healing and bone growth, cellular and hormonal factors play an important role. The purpose of this study was to non-invasively but quantitatively assess the effect of intraoperatively applied platelet-rich plasma (PRP) on the formation of cortical bone encircling the tibial tunnel. Patients and methods In fifty patients, standard arthroscopic ACL reconstructions were performed. The PRP group (n = 25) received a local application of PRP while the control group (n = 25) did not receive PRP. The proximal tibial tunnel was examined by MRI in the paraxial plane where the portion of the tibial tunnel wall circumference consisting of sclerotic cortical bone was assessed with testing occurring at one, two and a half and six months after surgery. Results At one month after surgery, differences between the groups in the amount of cortical sclerotic bone encircling the tunnel were not significant (p = 0.928). At two and a half months, the sclerotic portion of the tunnel wall in the PRP group (36.2%) was significantly larger than in the control (22.5%) group (p = 0.004). At six months, the portion of sclerotic bone in the PRP group (67.1%) was also significantly larger than in the control (53.5%) group (p = 0.003). Conclusions Enhanced cortical bone formation encircling the tibial tunnel at 2.5 and 6 months after ACL graft reconstruction results from locally applied platelet-rich plasma. PMID:23801907

Rupreht, Mitja; Vogrin, Matjaž; Hussein, Mohsen

2013-01-01

346

Identification of enoxacin as an inhibitor of osteoclast formation and bone resorption by structure-based virtual screening.  

PubMed

An interaction between the B2 subunit of vacuolar H(+)-ATPase (V-ATPase) and microfilaments is required for osteoclast bone resorption. An atomic homology model of the actin binding site on B2 was generated and molecular docking simulations were performed. Enoxacin, a fluoroquinolone antibiotic, was identified and in vitro testing demonstrated that enoxacin blocked binding between purified B2 and microfilaments. Enoxacin dose dependently reduced the number of osteoclasts differentiating in mouse marrow cultures stimulated with 1,25-dihydroxyvitamin D(3), as well as markers of osteoclast activity, and the number of resorption lacunae formed on bone slices. Enoxacin inhibited osteoclast formation at concentrations where osteoblast formation was not altered. In summary, enoxacin is a novel small molecule inhibitor of osteoclast bone resorption that acts by an unique mechanism and is therefore an attractive lead molecule for the development of a new class of antiosteoclastic agents. PMID:19630402

Ostrov, David A; Magis, Andrew T; Wronski, Thomas J; Chan, Edward K L; Toro, Edgardo J; Donatelli, Richard E; Sajek, Kristen; Haroun, Ireni N; Nagib, Michael I; Piedrahita, Ana; Harris, Ashley; Holliday, L Shannon

2009-08-27

347

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

PubMed Central

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

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

2014-01-01

348

Early Archean stromatolites: Paleoenvironmental setting and controls on formation  

NASA Technical Reports Server (NTRS)

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

Lowe, D. R.

1991-01-01

349

Sex-specific pattern formation during early Drosophila development.  

PubMed

The deleterious effects of different X-chromosome dosage in males and females are buffered by a process called dosage compensation, which in Drosophila is achieved through a doubling of X-linked transcription in males. The male-specific lethal complex mediates this process, but is known to act only after gastrulation. Recent work has shown that the transcription of X-linked genes is also upregulated in males prior to gastrulation; whether it results in functional dosage compensation is not known. Absent or partial early dosage compensation raises the possibility of sex-biased expression of key developmental genes, such as the segmentation genes controlling anteroposterior patterning. We assess the functional output of early dosage compensation by measuring the expression of even-skipped (eve) with high spatiotemporal resolution in male and female embryos. We show that eve has a sexually dimorphic pattern, suggesting an interaction with either X-chromosome dose or the sex determination system. By manipulating the gene copy number of an X-linked transcription factor, giant (gt), we traced sex-biased eve patterning to gt dose, indicating that early dosage compensation is functionally incomplete. Despite sex-biased eve expression, the gene networks downstream of eve are able to produce sex-independent segmentation, a point that we establish by measuring the proportions of segments in elongated germ-band embryos. Finally, we use a whole-locus eve transgene with modified cis regulation to demonstrate that segment proportions have a sex-dependent sensitivity to subtle changes in Eve expression. The sex independence of downstream segmentation despite this sensitivity to Eve expression implies that additional autosomal gene- or pathway-specific mechanisms are required to ameliorate the effects of partial early dosage compensation. PMID:23410834

Manu; Ludwig, Michael Z; Kreitman, Martin

2013-05-01

350

Quantitative computed tomography of vertebral spongiosa: a sensitive method for detecting early bone loss after oophorectomy  

SciTech Connect

The bone mineral loss was assessed serially in 37 premenopausal women for 24 months after oophorectomy and the dose-response for conjugated estrogen therapy in preventing this loss was determined. Spinal cancellous bone was measured by quantitative computed tomography and measurement of appendicular cortical bone by radial photon absorptiometry and metacarpal radiogrammetry. For the placebo and low-dose treatment groups, the mean annual bone mineral losses were 7% to 9% from the vertebral spongiosum and 1% to 3% from the peripheral cortex. The correlation between axial and appendicular loss was weak, precluding a reliable estimate of spinal loss from peripheral measurements. For the maximal-dose group (0.6 mg/d), the mean annual bone mineral losses were less than 0.5% from the axial and appendicular sites, and were not significant. The results indicate that spinal quantitative computed tomography provides a highly sensitive measurement of bone mineral loss after oophorectomy, that bone mineral loss is five- to sevenfold greater from the spinal spongiosum than from the appendicular cortex, and that conjugated estrogen in doses of less than 0.6 mg/d are inadequate to prevent the vertebral mineral loss.

Genant, H.K.; Cann, C.E.; Ettinger, B.; Gordan, G.S.

1982-11-01

351

Bone marrow cells recruited through the neuropilin-1 receptor promote arterial formation at the sites of adult neoangiogenesis in mice  

PubMed Central

Experimental and clinical evidence indicate that bone marrow cells participate in the process of new blood vessel formation. However, the molecular mechanisms underlying their recruitment and their exact role are still elusive. Here, we show that bone marrow cells are recruited to the sites of neoangiogenesis through the neuropilin-1 (NP-1) receptor and that they are essential for the maturation of the activated endothelium and the formation of arteries in mice. By exploiting adeno-associated virus vector–mediated, long-term in vivo gene expression, we show that the 165-aa isoform of VEGF, which both activates the endothelium and recruits NP-1+ myeloid cells, is a powerful arteriogenic agent. In contrast, neither the shortest VEGF121 isoform, which does not bind NP-1 and thus does not recruit bone marrow cells, nor semaphorin 3A, which attracts cells but inhibits endothelial activation, are capable of sustaining arterial formation. Bone marrow myeloid cells are not arteriogenic per se nor are they directly incorporated in the newly formed vasculature, but they contribute to arterial formation through a paracrine effect ensuing in the activation and proliferation of tissue-resident smooth muscle cells. PMID:18483621

Zacchigna, Serena; Pattarini, Lucia; Zentilin, Lorena; Moimas, Silvia; Carrer, Alessandro; Sinigaglia, Milena; Arsic, Nikola; Tafuro, Sabrina; Sinagra, Gianfranco; Giacca, Mauro

2008-01-01

352

Secreted Phosphoprotein 24 kD (Spp24) and Spp14 Affect TGF-? Induced Bone Formation Differently  

PubMed Central

Transforming growth factor-? (TGF-?) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-?1 and TGF-?2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-? with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-?2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-?2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-? administration in vivo is associated with greater bone formation than high-dose TGF-? administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-? activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-? compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders. PMID:23991133

Tian, Haijun; Bi, Xiaoda; Li, Chen-Shuang; Zhao, Ke-Wei; Brochmann, Elsa J.; Montgomery, Scott R.; Aghdasi, Bayan; Chen, Deyu; Daubs, Michael D.; Wang, Jeffrey C.; Murray, Samuel S.

2013-01-01

353

A model for core formation in the early Earth  

Microsoft Academic Search

Two basic types exogenous models were proposed to account for siderophile and chalcophile element abundances in the Earth's upper mantle. The first model requires that the Earth be depleted in volatiles and that, after a core formation event which extracted the most siderophile elements into the core, additional noble siderophile elements (Pt, Ir, Au) were added as a late veneer

J. H. Jones; M. J. Drake

1985-01-01

354

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

PubMed Central

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

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

2014-01-01

355

Balancing the rates of new bone formation and polymer degradation enhances healing of weight-bearing allograft/polyurethane composites in rabbit femoral defects.  

PubMed

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

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

2014-01-01

356

Altered gallbladder concentration of biliary lipids during early cholesterol gallstone formation  

Microsoft Academic Search

Whether gallbladder absorptive function is altered during formation of cholesterol gallstones is unclear. We tested the hypothesis that alterations in biliary lipid composition present during early cholesterol gallstone formation enhance gallbladder absorption, as manifested by an increase in the ratio of gallbladder to hepatic bile lipid concentrations. Prairie dogs received either control or a 0.4% cholesterol-enriched chow for two or

Joel J. Roslyn; Robert L. Conter; Lawrence DenBesten

1987-01-01

357

Lecture notes on the formation and early evolution of planetary systems  

E-print Network

These notes provide an introduction to the theory of the formation and early evolution of planetary systems. Topics covered include the structure, evolution and dispersal of protoplanetary disks; the formation of planetesimals, terrestrial and gas giant planets; and orbital evolution due to gas disk migration, planetesimal scattering, planet-planet interactions, and tides.

Philip J. Armitage

2014-08-26

358

Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6.  

PubMed

Aging purportedly diminishes the ability of the skeleton to respond to mechanical loading, but recent data show that old age did not impair loading-induced accrual of bone in BALB/c mice. Here, we hypothesized that aging limits the response of the tibia to axial compression over a range of adult ages in the commonly used C57BL/6. We subjected the right tibia of old (22 month), middle-aged (12 month) and young-adult (5 month) female C57BL/6 mice to peak periosteal strains (measured near the mid-diaphysis) of -2200 ?? and -3000 ?? (n=12-15/age/strain) via axial tibial compression (4 Hz, 1200 cycles/day, 5 days/week, 2 weeks). The left tibia served as a non-loaded, contralateral control. In mice of every age, tibial compression that engendered a peak strain of -2200 ?? did not alter cortical bone volume but loading to a peak strain of -3000 ?? increased cortical bone volume due in part to woven bone formation. Both loading magnitudes increased total volume, medullary volume and periosteal bone formation parameters (MS/BS, BFR/BS) near the cortical midshaft. Compared to the increase in total volume and bone formation parameters of 5-month mice, increases were less in 12- and 22-month mice by 45-63%. Moreover, woven bone incidence was greatest in 5-month mice. Similarly, tibial loading at -3000 ?? increased trabecular BV/TV of 5-month mice by 18% (from 0.085 mm3/mm3), but trabecular BV/TV did not change in 12- or 22-month mice, perhaps due to low initial BV/TV (0.032 and 0.038 mm3/mm3, respectively). In conclusion, these data show that while young-adult C57BL/6 mice had greater periosteal bone formation following loading than middle-aged or old mice, aging did not eliminate the ability of the tibia to accrue cortical bone. PMID:24836737

Holguin, Nilsson; Brodt, Michael D; Sanchez, Michelle E; Silva, Matthew J

2014-08-01

359

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

PubMed Central

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

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

2010-01-01

360

Leukemia Inhibitory Factor Secretion is a Predictor and Indicator of Early Progenitor Status in Adult Bone Marrow Stromal Cells  

PubMed Central

Bone marrow–derived stromal cells (BMSCs) are defined by their ability to self-renew and differentiate into at least three mesenchymal cell types (bone, adipose, and cartilage). The inability to isolate a reliably efficacious and homogeneous population of early progenitor cells has limited efforts to increase their therapeutic potential. In this study, we focused on identifying protein markers that may be employed to predict the efficacy of a cultured BMSC population. Markers of progenitor status were identified by comparing BMSCs at early and late passage, donor-matched skin fibroblasts, and commercially available dermal fibroblast cell lines. Differentiation potential was determined according to in vitro assays of osteogenesis, adipogenesis, and chondrogenesis. Early-passage BMSCs differentiated into all three lineages, whereas late-passage BMSCs and both fibroblast preparations did not. To identify novel markers of early progenitors, microarray transcript analysis between early-passage BMSCs and fibroblasts was performed. Messenger RNA encoding the cytokine leukemia inhibitory factor (LIF) was identified as differentially expressed. Enzyme-linked immunosorbent assay on conditioned media confirmed that LIF secretion was much higher from early progenitor BMSCs than donor-matched or commercial lines of fibroblasts and dropped with extensive expansion or induction of differentiation. In clonally expanded BMSCs, colonies that retained progenitor status expressed significantly higher levels of LIF than those that failed to differentiate. Our results indicate that LIF expression may represent a marker to quantify the differentiation potential of BMSCs and may be especially suited for the rapid, noninvasive quality control of clinical preparations. PMID:18637760

Whitney, Mandolin J.; Lee, Andy; Ylostalo, Joni; Zeitouni, Suzanne; Tucker, Alan

2009-01-01