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1

Biphasic electrical current stimulator for early bone formation in dental implant  

Microsoft Academic Search

Since the discovery of piezoelectric properties of natural bone, electrical stimulation has been widely used in the clinical treatment of orthopedic fracture. Nevertheless, in dental implant technologies, it is the methods of surface modification that has been recently developed to enhance early osteointegration between implant's surface and surrounding tissue. In this paper, in order to accelerate bone formation, we developed

Jong Keun Song; Sung June Kim

2

Light-emitting diode photobiomodulation: effect on bone formation in orthopedically expanded suture in rats--early bone changes.  

PubMed

The aim of this experimental study was to evaluate histomorphometrically the effects of light-emitting diode (LED) photobiomodulation therapy (LPT) on bone formation in response to expansion of the interpremaxillary suture in rats. Twenty male, 50- to 60-day-old Wistar rats were divided into two equal groups (control and experimental). Both groups were subjected to expansion for 5 days, and 50 cN of force was applied to the maxillary incisors with helical spring. An OsseoPulse® LED device, 618-nm wavelength and 20-mW/cm(2) output power irradiation, was applied to the interpremaxillary suture for 10 days. Bone formation in the sutural area was histomorphometrically evaluated, including the amount of new bone formation (in square micrometers), number of osteoblasts, number of osteoclasts, and number of vessels. Mann-Whitney U test was used for statistical evaluation at p?bone formation area (p?=?0.024, 1.48-fold), number of osteoblasts (p?Bone histomorphometric measurements revealed that bone architecture in the LPT group was improved. The application of LPT can stimulate bone formation in the orthopedically expanded interpremaxillary suture during expansion and the early phase of the retention periods. PMID:23139069

Ekizer, Abdullah; Uysal, Tancan; Güray, Enis; Yüksel, Yasemin

2013-09-01

3

The transcription factor early B-cell factor 1 regulates bone formation in an osteoblast-nonautonomous manner  

PubMed Central

Early B-cell factor 1 (Ebf1) is a transcription factor whose inactivation in all cells results in high bone mass because of an increase in bone formation. This observation suggests Ebf1 may be an inhibitor of osteoblast differentiation. To test this contention, we analyzed Ebf1 pattern of expression and function in osteoblasts ex vivo and in vivo through osteoblast-specific inactivation in the mouse. We show here that in vivo deletion of Ebf1 in osteoblast progenitors does not affect osteoblast differentiation or bone formation accrual post-natally. These observations indicate that the phenotype described in Ebf1?/? mice is not osteoblast-autonomous.

Zee, Tiffany; Boller, Soren; Gyory, Ildiko; Makinistoglu, Munevver P.; Tuckermann, Jan P.; Grosschedl, Rudolf; Karsenty, Gerard

2014-01-01

4

Central control of bone formation  

Microsoft Academic Search

Vertebrates constantly remodel bone to maintain a constant bone mass. Bone remodeling comprises two phases: bone resorption\\u000a by the osteoclasts followed by bone formation by the osteoblasts. Although the prevailing view about the control of bone remodeling\\u000a is that it is an autocrine\\/paracrine phenomenon, the bone resorption arm of bone remodeling is under a tight endocrine control.\\u000a To date little

Shu Takeda; Gerard Karsenty

2001-01-01

5

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

Microsoft Academic Search

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

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

2007-01-01

6

Bone formation by cancer metastases  

Microsoft Academic Search

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

U. Bettendorf; W. Remmele; H. Laaff

1976-01-01

7

Early Bone Healing Events following Rat Molar Tooth Extraction  

Microsoft Academic Search

Healing of the rat tooth extraction socket occurs rapidly, indicating a mechanism for cancellous bone formation occurring swiftly throughout the matrix. The residual periodontal ligament is evident at 2 days after extraction and its rich collagen type III fibre content may form a template for future cancellous bone formation. In the remainder of the early tooth extraction socket, fibronectin staining

Hugh Devlin

2000-01-01

8

Dilatational band formation in bone  

PubMed Central

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

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

2012-01-01

9

Inhibition of bone formation during space flight  

NASA Technical Reports Server (NTRS)

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

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

1978-01-01

10

Changes in lipids during matrix: Induced endochondral bone formation  

Microsoft Academic Search

Summary  The changes in lipids occurring during the process of endochondral ossification have been characterized by studying the discrete\\u000a phases of matrix-induced endochondral bone formation in the rat. Calcium-acidic phospholipid-phosphate complexes were shown\\u000a to increase in concentration during cartilage calcification (day 9) and to peak in content during early bone formation (day\\u000a 11–13), the times during which the rate of mineral

A. L. Boskey; A. H. Reddi

1983-01-01

11

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  

Microsoft Academic Search

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

Paul Anthony; Henry Keys; C. McCollister Evarts; Philip Rubin; Carol Lush

1987-01-01

12

Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-2.  

PubMed

It has previously been shown that mice with a defect in Fas ligand-mediated apoptosis have an enhancement of ectopic bone formation. We investigated the expression of bone-related markers--alkaline phosphatase, collagen, bone sialoprotein, osteocalcin, osteopontin, and bone morphogenetic proteins (BMP) -2, -4, and -7; and cytokines interleukin-1alpha (IL-1), IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) in ectopic new bone induced by recombinant human (rh) BMP-2 in mice without functional Fas-ligand (gld mice). At day 6 after rhBMP-2 implantation, gld mice formed more cartilage and mesenchyme compared with their wild type littermates. At later stages, gld mice did not differ from the control mice in the volume of newly formed tissue, expressing higher level of BMP genes and lower levels of genes involved in osteoblast maturation--bone sialoprotein and osteopontin. Differences in the levels of expression of IL-1alpha and TNF-alpha were observed only at day 12 after rhBMP-2 implantation. These results suggest that gld mice have an increased recruitment of cells of mesenchymal origin and an abnormal pattern of differentiation and maturation of the newly formed mesenchymal tissues. PMID:14575809

Katavi?, Vedran; Grcevi?, Danka; Luki?, Ivan Kresimir; Vucenik, Vladimira; Kovaci?, Natasa; Kalajzi?, Ivo; Marusi?, Ana

2003-11-21

13

Therapeutic inhibition of cathepsin K--reducing bone resorption while maintaining bone formation  

PubMed Central

Osteoporosis is a disease of high bone remodeling with an imbalance of bone resorption over bone formation, resulting in decreased bone mineral density and deterioration of bone microarchitecture. From the emerging understandings of the molecular and cellular regulators of bone remodeling, potential new targets for therapeutic intervention for this disease have been identified. Cathepsin K (CatK), a cysteine protease produced by osteoclasts, is the primary enzyme mediating the degradation of the demineralized bone matrix. Current genetic and pharmacological evidence from studies in multiple preclinical species have consistently demonstrated that inhibition of CatK results in the reduction of bone resorption while allowing bone formation to continue. Early results from clinical studies with several investigational CatK inhibitors indicate that the impact of CatK inhibition on bone formation is distinct from that of either the bisphosphonates or the anti-receptor activator of nuclear factor-?B ligand antibody, denosumab. Odanacatib, a highly selective, reversible and potent inhibitor of CatK, is currently in phase III clinical trials for the treatment of postmenopausal osteoporosis.

Duong, Le T

2012-01-01

14

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

15

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

16

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

17

Inherited human diseases of heterotopic bone formation  

PubMed Central

Human disorders of hereditary and nonhereditary heterotopic ossification are conditions in which osteogenesis occurs outside of the skeleton, within soft tissues of the body. The resulting extraskeletal bone is normal. The aberration lies within the mechanisms that regulate cell-fate determination, directing the inappropriate formation of cartilage or bone, or both, in tissues such as skeletal muscle and adipose tissue. Specific gene mutations have been identified in two rare inherited disorders that are clinically characterized by extensive and progressive extraskeletal bone formation—fibrodysplasia ossificans progressiva and progressive osseous heteroplasia. In fibrodysplasia ossificans progressiva, activating mutations in activin receptor type-1, a bone morphogenetic protein type I receptor, induce heterotopic endochondral ossification, which results in the development of a functional bone organ system that includes skeletal-like bone and bone marrow. In progressive osseous heteroplasia, the heterotopic ossification leads to the formation of mainly intramembranous bone tissue in response to inactivating mutations in the GNAS gene. Patients with these diseases variably show malformation of normal skeletal elements, identifying the causative genes and their associated signaling pathways as key mediators of skeletal development in addition to regulating cell-fate decisions by adult stem cells.

Shore, Eileen M.; Kaplan, Frederick S.

2013-01-01

18

Clay-Enriched Silk Biomaterials for Bone Formation  

PubMed Central

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

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

2011-01-01

19

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

20

In vitro bone formation on coral granules  

Microsoft Academic Search

Summary  We investigated the ability of fetal rat bone cells isolated after collagenase digestion to differentiate in vitro and to\\u000a produce a mineralized matrix on coral granules. Scanning electron microscopy examination of the surface of the seeded coral\\u000a granules revealed that cells attached, spread, and proliferated on the material surface. Bone nodule formation was studied\\u000a in this in vitro system by

J. M. Sautier; J. R. Nefussi; H. Boulekbache; N. Forest

1990-01-01

21

Novel Regulators of Bone Formation: Molecular Clones and Activities  

Microsoft Academic Search

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

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

1988-01-01

22

[BMP signaling and bone formation].  

PubMed

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

Katagiri, Takenobu

2012-11-01

23

?-catenin Promotes Bone Formation And Suppresses Bone Resorption in Postnatal Growing Mice  

PubMed Central

Genetic studies in the mouse have demonstrated multiple roles for ?-catenin in the skeleton. In the embryo, ?-catenin is critical for the early stages of osteoblast differentiation. Postnatally, ?-catenin in mature osteoblasts and osteocytes indirectly suppresses osteoclast differentiation. However, a direct role for ?-catenin in regulating osteoblast number and/or function specifically in the postnatal life has not been demonstrated. Addressing this knowledge gap is important because LRP5, a co-receptor for WNT signaling proposed to function through ?-catenin, controls osteoblast number and function in postnatal mice or humans. To overcome the neonatal lethality caused by embryonic deletion of ?-catenin in early-stage osteoblast-lineage cells, we utilize Osx-CreERT2 to remove ?-catenin in Osx-expressing cells by administering tamoxifen (TM) temporarily to postnatal mice. Lineage-tracing experiments in the long bones demonstrate that Osx-CreERT2 targets predominantly osteoblast-lineage cells on the bone surface, but also transient progenitors that contribute to bone marrow stromal cells and adipocytes. Deletion of ?-catenin by this strategy greatly reduces the bone formation activity of the targeted osteoblasts. However, the targeted osteoblasts rapidly turn over and are replaced by an excessive number of non-targeted osteoblasts, causing an unexpected increase in bone formation, but an even greater increase in osteoclast number and activity produces a net effect of severe osteopenia. With time, the mutant mice also exhibit a marked increase in bone marrow adiposity. Thus, ?-catenin in postnatal Osx-lineage cells critically regulates bone homeostasis by promoting osteoblast activity and suppressing osteoblast turnover, while restraining osteoclast and marrow fat formation.

Chen, Jianquan; Long, Fanxin

2012-01-01

24

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

PubMed Central

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

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

2013-01-01

25

Exposure to omega-3 fatty acids at early age accelerate bone growth and improve bone quality.  

PubMed

Omega-3 fatty acids (FAs) are essential nutritional components that must be obtained from foods. Increasing evidence validate that omega-3 FAs are beneficial for bone health, and several mechanisms have been suggested to mediate their effects on bone, including alterations in calcium absorption and urinary calcium loss, prostaglandin synthesis, lipid oxidation, osteoblast formation and inhibition of osteoclastogenesis. However, to date, there is scant information regarding the effect of omega-3 FAs on the developing skeleton during the rapid growth phase. In this study we aim to evaluate the effect of exposure to high levels of omega-3 FAs on bone development and quality during prenatal and early postnatal period. For this purpose, we used the fat-1 transgenic mice that have the ability to convert omega-6 to omega-3 fatty acids and the ATDC5 chondrogenic cell line as models. We show that exposure to high concentrations of omega-3 FAs at a young age accelerates bone growth through alterations of the growth plate, associated with increased chondrocyte proliferation and differentiation. We further propose that those effects are mediated by the receptors G-protein coupled receptor 120 (GPR120) and hepatic nuclear factor 4?, which are expressed by chondrocytes in culture. Additionally, using a combined study on the structural and mechanical bone parameters, we show that high omega-3 levels contribute to superior trabecular and cortical structure, as well as to stiffer bones and improved bone quality. Most interestingly, the fat-1 model allowed us to demonstrate the role of maternal high omega-3 concentration on bone growth during the gestation and postnatal period. PMID:24746838

Koren, Netta; Simsa-Maziel, Stav; Shahar, Ron; Schwartz, Betty; Monsonego-Ornan, Efrat

2014-06-01

26

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

27

Antiangiogenic Agent (TNP470) Inhibition of Ectopic Bone Formation Induced by Bone Morphogenetic Protein2  

Microsoft Academic Search

Bone morphogenetic protein (BMP) is a potent inducer of ectopic bone formation, and TNP-470, a synthetic analog of fumagillin, is an antiangiogenic agent that strongly inhibits neovascular formation in vivo. We investigated the effects of TNP-470 on BMP-induced ectopic bone formation to clarify the role of angiogenesis in bone formation. Collagen pellets containing recombinant human BMP-2 (rhBMP-2) were implanted beneath

S Mori; H Yoshikawa; J Hashimoto; T Ueda; H Funai; M Kato; K Takaoka

1998-01-01

28

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

SciTech Connect

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

Goodman, W.G.

1984-05-01

29

Early tissue responses to zoledronate, locally delivered by bone screw, into a compromised cancellous bone site: a pilot study  

PubMed Central

Background In fracture treatment, adequate fixation of implants is crucial to long-term clinical performance. Bisphosphonates (BP), potent inhibitors of osteoclastic bone resorption, are known to increase peri-implant bone mass and accelerate primary fixation. However, adverse effects are associated with systemic use of BPs. Thus, Zoledronic acid (ZOL) a potent BP was loaded on bone screws and evaluated in a local delivery model. Whilst mid- to long-term effects are already reported, early cellular events occurring at the implant/bone interface are not well described. The present study investigated early tissue responses to ZOL locally delivered, by bone screw, into a compromised cancellous bone site. Methods ZOL was immobilized on fibrinogen coated titanium screws. Using a bilateral approach, ZOL loaded test and non-loaded control screws were implanted into femoral condyle bone defects, created by an overdrilling technique. Histological analyses of the local tissue effects such as new bone formation and osteointegration were performed at days 1, 5 and 10. Results Histological evaluation of the five day ZOL group, demonstrated a higher osseous differentiation trend. At ten days an early influx of mesenchymal and osteoprogenitor cells was seen and a higher level of cellular proliferation and differentiation (p?bone-to-screw contact and bone volume values within the defect tended to increase. Local drug release did not induce any adverse cellular effects. Conclusion This study indicates that local ZOL delivery into a compromised cancellous bone site actively supports peri-implant osteogenesis, positively affecting mesenchymal cells, at earlier time points than previously reported in the literature.

2014-01-01

30

Stimulation of bone marrow cells and bone formation by nacre: in vivo and in vitro studies  

Microsoft Academic Search

There is frequently a loss of vertebral bone due to disease or aging. Nacre (mother of pearl from the oyster Pinctada maxima) stimulates bone cell differentiation and bone formation in vitro and in vivo. Experimental bone defects were prepared in the vertebrae of sheep and used to test the suitability of nacre as an injectable osteogenic biomaterial for treating vertebral

M Lamghari; M. J Almeida; S Berland; H Huet; A Laurent; C Milet; E Lopez

1999-01-01

31

Distal radial fractures heal by direct woven bone formation  

PubMed Central

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

2013-01-01

32

Eldecalcitol and calcitriol stimulates 'bone minimodeling,' focal bone formation without prior bone resorption, in rat trabecular bone.  

PubMed

Vitamin D is known as a potent stimulator of bone resorption. The active form of vitamin D3, calcitriol (1?,25-dihydroxyvitamin D3), stimulates release of calcium (Ca) from bone in ex vivo organ culture, and treatment with large amounts of an active vitamin D3 analog induces hypercalcemia and bone resorption in mice in vivo. Calcitriol strongly induces both receptor activator of NF-?B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in osteoblasts in vitro. On the other hand, it has been reported that active vitamin D3 inhibits bone resorption in various experimental animal models. We previously showed that eldecalcitol [1?,25-dihydroxy-2?-(3-hydroxy-propyloxy)vitamin D3; ED-71] suppresses bone resorption and increases bone mineral density (BMD) to a greater extent than alfacalcidol (1?-hydroxyvitamin D3) in ovariectomized (OVX) rats in vivo. To elucidate the histological events that follow administration of eldecalcitol compared to calcitriol, OVX rats were given either vehicle, eldecalcitol (10, 30, or 90ng/kg), or calcitriol (33.3, 100, 300, or 900ng/kg), and sham-operated control animals were given vehicle, 5-times per week for 12 weeks. The lumbar spine and femur were removed and processed for bone mineral density (BMD) assessments and the femur for histomorphometrical analyzes. Both eldecalcitol and calcitriol increased the lumbar and femoral BMD in a dose dependent manner. Bone histomorphometry revealed that osteoclast surface (Oc.S/BS) and eroded surface (ES/BS) were dose-dependently suppressed in the trabecular region of the femur. Both calcitriol and eldecalcitol dose-dependently stimulated focal bone formation that started without prior bone resorption, a process known as bone minimodeling. Both reduction of bone resorption and stimulation of focal bone formation were more clearly observed in the eldecalcitol-treated rats than in the calcitriol-treated rats. Taken together, these findings suggest that eldecalcitol is a more potent vitamin D3 analog that stimulates focal bone formation (minimodeling) and suppresses bone resorption more strongly than does calcitriol. This article is part of a Special Issue entitled 'Vitamin D Workshop'. PMID:23069645

Saito, Hitoshi; Takeda, Satoshi; Amizuka, Norio

2013-07-01

33

Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix  

PubMed Central

Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone.

Baek, Wook-Young; Lee, Min-A; Jung, Ji Won; Kim, Shin-Yoon; Akiyama, Haruhiko; de Crombrugghe, Benoit; Kim, Jung-Eun

2014-01-01

34

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

PubMed Central

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

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

2012-01-01

35

Demineralization of the contacting surfaces in autologous onlay bone grafts improves bone formation and bone consolidation.  

PubMed

Background: Autologous bone grafts are usually well consolidated after 4 to 5 months but can be incompletely interlocked with the native bone. This study investigated the effect of acid demineralization of the graft-bed interface on graft consolidation. Methods: Onlay bone grafts were performed on the calvaria of 36 guinea pigs. Half of the animals had the graft-bed contacting surfaces demineralized with 50% citric acid (pH 1.0) for 3 minutes (test group). The other half received no demineralization (control group). The bone grafts were immobilized by a resorbable membrane glued to the recipient bed with cyanoacrylate. After 7, 30, and 90 days, specimens (n = 6) were obtained for light microscopy. Data from qualitative analysis and computerized histomorphometry were statistically processed at a significance level of 5%. Results: Osteogenesis was not seen at the interface after 7 days. After 30 days, the test group showed 34.39% ± 13.4% of the interface area filled with mineralized tissue, compared to 17.14% ± 8.6% in the control group (P = 0.026). After 90 days, the mean percentages of mineralized tissue at the interface in the test and control specimens were 54.00% ± 11.23% and 38.65% ± 7.76% (P = 0.041), respectively. Within groups, a higher percentage of the area filled with mineralized tissue was seen at 90 days compared to 30 days (P = 0.004 for control and 0.041 for test). Conclusions: Demineralization of the contacting surfaces between autologous bone graft and bone bed improved new bone formation and bone consolidation. These data need to be confirmed in humans. PMID:24171500

Rezende, Maria L; Consolaro, Alberto; Sant'ana, Adriana C; Damante, Carla A; Greghi, Sebastião L; Passanezi, Euloir

2014-05-01

36

Effect of spaceflight on periosteal bone formation in rats  

NASA Technical Reports Server (NTRS)

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

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

1983-01-01

37

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

38

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

39

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

NASA Technical Reports Server (NTRS)

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

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

1983-01-01

40

Glucocorticoids and inhibition of bone formation induced by skeletal unloading  

SciTech Connect

Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of {sup 45}Ca and ({sup 3}H)proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly.

Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E. (Univ. of California, San Francisco (USA) Veterans Administration Medical Center, San Francisco, CA (USA) NASA-Ames Research Center, Moffett Field, CA (USA))

1988-12-01

41

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

42

Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation, osteoclast recruitment, and bone turnover.  

PubMed

Reconstruction of craniofacial defects presents a substantial biomedical burden, and requires complex surgery. Interestingly, children after age 2 years and adults are unable to heal large skull defects. This nonhealing paradigm provides an excellent model system for craniofacial skeletal tissueengineering strategies. Previous studies have documented the in vivo osteogenic potential of adipose-derived stromal (ADS) cells and bone marrow-derived stromal (BMS) cells. This study investigates the ability to accelerate in vivo osteogenesis on ex vivo recombinant human bone morphogenetic protein 2 (BMP-2) and retinoic acid stimulation. Mouse osteoblasts, ADS cells, and BMS cells were seeded onto apatite-coated PLGA scaffolds, stimulated with rhBMP-2 and retinoic acid ex vivo for 4 weeks, and subsequently implanted into critically sized (4 mm) calvarial defects. Samples were harvested after 2, 4, 8, and 12 weeks. Areas of complete bony bridging were noted as early as 2 weeks in vivo; however, osteoclasts were attracted to the scaffold as identified by calcitonin receptor staining and tartrate-resistant acid phosphatase activity staining. Although the optimal method of in vitro osteogenic priming for mesenchymal cells remains unknown, these results provide evidence that BMP-2 and retinoic acid stimulation of multipotent cells ex vivo can subsequently induce significant quantities of bone formation within a short time period in vivo. PMID:15869441

Cowan, Catherine M; Aalami, Oliver O; Shi, Yun-Ying; Chou, Yu-Fen; Mari, Carina; Thomas, Romy; Quarto, Natalin; Nacamuli, Randall P; Contag, Christopher H; Wu, Benjamin; Longaker, Michael T

2005-01-01

43

Early chronic kidney disease-mineral bone disorder stimulates vascular calcification  

PubMed Central

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

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

2013-01-01

44

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

45

In vivo tracking of segmental bone defect healing reveals that callus patterning is related to early mechanical stimuli.  

PubMed

This study addresses the hypothesis that callus formation, patterning, and mineralisation are impaired during the early phase of critical sized bone defect healing, and may relate to inter-fragmentary tissue strains within the bone defect area. Twenty four 12 week old Sprague Dawley rats were used for this study. They were divided into two groups defined by the femur bone defect size: (i) 1 mm resulting in normal healing (NH), and (ii) a large sized 5 mm defect resulting in critical healing (CH). Callus formation, patterning, and mineralisation kinetics in both groups were examined in the periosteal and osteotomy gap regions using a novel longitudinal study setup. Finite element analyses on µCT generated tomograms were used to determine inter-fragmentary tissue strain patterns and compared to callus formation and patterning over the course of time. Using a novel longitudinal study technique with µCT, in vivo tracking and computer simulation approaches, this study demonstrates that: (i) periosteal bone formation and patterning are significantly influenced by bone defect size as early as 2 weeks; (ii) osteotomy gap callus formation and patterning are influenced by bone defect size, and adapt towards a non-union in critical cases by deviating into a medullary formation route as early as 2 weeks after osteotomy; (iii) the new bone formation in the osteotomy gap enclosing the medullary cavity in the CH group is highly mineralised; (iv) inter-fragmentary strain patterns predicted during the very early soft callus tissue phase (less than 2 weeks) are concurrent with callus formation and patterning at later stages. In conclusion, bone defect size influences early onset of critical healing patterns. PMID:23124984

Mehta, Manav; Checa, Sara; Lienau, Jasmin; Hutmacher, Dietmar; Duda, Georg N

2012-01-01

46

Bone Formation by BMP Gene Transfection  

NASA Astrophysics Data System (ADS)

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

Kishimoto, Koshi N.; Watanabe, Yuji

47

Role of B lymphocytes in new bone formation.  

PubMed

Although there may be a close relationship between B lymphocytes and osteoclasts, or bone resorbing cells, little is known about the role of B lymphocytes in bone formation. We compared in vivo new bone induction in mice homozygous for the B-cell deficient (microMT) gene knockout, which lack functional B lymphocytes, with bone induction in control wild-type (C57BL/6) mice. Our comparison used two models of new bone induction in vivo: endochondral osteoinduction by subcutaneous implantation of recombinant human bone morphogenetic protein (rhBMP-2) and osteogenic regeneration after tibial bone marrow ablation. The expression of bone-specific proteins (bone sialoprotein, osteopontin, and osteocalcin) and inflammatory/immunomodulatory cytokines (interleukin-1alpha and -1beta, interleukin-6, and tumor necrosis factor-alpha) was assessed by Northern blot analysis or reverse transcription-polymerase chain reaction, respectively. Ossicles induced by rhBMP-2 were larger in volume and mass in microMT knockout mice, but relative volumes of the newly induced bone, cartilage, and bone marrow were similar in the two groups. Six days after tibial bone marrow ablation, microMT knockout mice resorbed the initial blood clot faster and formed more trabecular bone, paralleled by greater levels of bone sialoprotein mRNA than in the wild-type mice. microMT knockout and wild-type mice also differed in the expression pattern of inflammatory/immunomodulatory cytokines during the development of the newly induced bone, suggesting that a genetic lack of B lymphocytes may create a change in the immunological milieu at the site of new bone induction, which stimulates the initial accumulation and proliferation of mesenchymal progenitor. PMID:11092536

Marusic, A; Grcevic, D; Katavic, V; Kovacic, N; Lukic, I K; Kalajzic, I; Lorenzo, J A

2000-11-01

48

Early active mobilization following UCL repair With Mitek bone anchor.  

PubMed

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

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

2013-09-01

49

Effect of Buguzhi (Psoralea corylifolia fruit) extract on bone formation.  

PubMed

The objective of the study is to compare the amount of new bone produced by Buguzhi (Psoralea corylifolia fruit) extract in collagen matrix to that produced and collagen matrix in vivo. Eighteen bone defects, 5 mm by 10 mm, were created in the parietal bone of 9 New Zealand white rabbits. Six defects were grafted with Buguzhi extract mixed with collagen matrix. Six defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were sacrificed on day 14 and the defects were dissected and prepared for histological assessment. Quantitative analysis of new bone formation and bone cells was made on 100 sections (50 sections for each group) using image analysis. A total of 275% more new bone was present in defects grafted with Buguzhi extract in collagen matrix than those grafted with collagen matrix. No bone was formed in the negative control group. The amount of bone cells was also significantly greater in the Buguzhi group than in the positive control group. To conclude, Buguzhi extract in collagen matrix has the effect of increasing new bone formation locally in vivo. Buguzhi extract in collagen matrix can be used as a bone graft material. PMID:19953524

Wong, R W K; Rabie, A B M

2010-06-01

50

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

51

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys  

NASA Technical Reports Server (NTRS)

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

Cann, Christopher; Young, Donald R.

1976-01-01

52

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

PubMed Central

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

2010-01-01

53

Heterotopic bone formation (myositis ossificans) and lower-extremity swelling mimicking deep-venous disease  

SciTech Connect

A quadriplegic patient with a swollen leg was suspected of having deep-venous thrombosis, and was studied with radionuclide venography (RNV) and contrast venography. Focal narrowing of the femoral vein, seen on RNV, was due to extrinsic compression. Although soft-tissue radiographs were normal, Tc-99m diphosphonate imaging established the diagnosis of early heterotopic bone formation (myositis ossificans), which was responsible for the venous compression. Clinically this inflammatory process can mimic deep-venous thrombosis, and should be considered in evaluating patients at risk for both heterotopic bone formation and deep-venous thrombosis.

Orzel, J.A.; Rudd, T.G.; Nelp, W.B.

1984-10-01

54

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

55

Lrp5 and bone formation : A serotonin-dependent pathway.  

PubMed

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

Yadav, Vijay K; Ducy, Patricia

2010-03-01

56

Heterotopic bone formation following hip arthroplasty in Paget's disease.  

PubMed

Heterotopic bone formation in soft tissues occurs commonly in Paget's disease patients following a primary total hip arthroplasty (THA). The nature of this heterotopic bone has not been documented. In this report, we show that the heterotopic bone removed 14 years after primary THA in a case of Paget's disease was sclerotic, contained prominent mosaic cement lines and showed increased remodelling activity on the bone surface. In addition to these typically Pagetic histological features, it was noted ultrastructurally that the osteoclasts contained characteristic intranuclear viral-like inclusions. In contrast, the foreign body macrophages found in the joint pseudocapsule and pseudomembrane, which are a population of mononuclear precursor cells from which osteoclasts can be formed, did not contain viral-like inclusions. These findings are of interest regarding the pathogenesis of heterotopic bone formation following hip arthroplasty and the ontogeny of Pagetic osteoclasts. PMID:15260016

Ferguson, D J P; Itonaga, I; Maki, M; McNally, E; Gundle, R; Athanasou, N A

2004-06-01

57

Endochondral bone formation in embryonic mouse pre-metatarsals  

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

58

Bone density and brain atrophy in early Alzheimer's disease.  

PubMed

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, gender, 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]). BMD 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 AD. PMID:19661621

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

2009-01-01

59

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.

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

2013-01-01

60

Estrogen maintains trabecular bone volume in rats not only by suppression of bone resorption but also by stimulation of bone formation.  

PubMed Central

Estrogen is generally considered to maintain bone mass through suppression of bone resorption. We have previously demonstrated that administration of pharmacologic doses of estrogen increases bone formation in ovary-intact rats. To assess the effects of physiological concentrations of estrogen on bone formation, estrogen was administered to ovariectomized rats in which bone resorption was suppressed by the bisphosphonate 3-amino-1-hydroxypropylidene-1-bisphosphonate (AHPrBP). Animals receiving exogenous 17 beta-estradiol (E2) (1, 10, and 100 micrograms/kg daily for 17 d) showed a dose-dependent increase in trabecular bone volume of 1.9, 25.8, and 43.6%, respectively, compared with those rats treated with AHPrBP alone. The increase in bone volume was associated with an increase in bone formation in E2-treated animals, in which bone resorption had been almost completely suppressed by AHPrBP. Neither ovariectomy, AHPrBP, nor E2 treatment had a significant effect on the volume or rate of formation of cortical bone. Thus, the increased bone resorption, which is a consequence of estrogen-deficiency, entrains increased bone formation, which masks a simultaneous reduction in estrogen-dependent bone formation. Therefore, in addition to the nonspecific effect of estrogen to depress formation via coupling, we have identified a specific effect of estrogen to increase formation independent of coupling. Thus it appears that estrogen maintains bone volume not only through inhibition of bone resorption, but also through stimulation of bone formation. Images

Chow, J; Tobias, J H; Colston, K W; Chambers, T J

1992-01-01

61

Stimulatory effects of low-power laser irradiation on bone formation in vitro  

NASA Astrophysics Data System (ADS)

The effect of low-power laser irradiation on bone formation in vitro were assessed. Osteoblast-like cells were isolated from rat calvariae of 21d rat fetuses. The cultured calvarial cells were irradiated with a low-power laser (830 nm, 60 mW) one time only or once daily for 21d at various energy doses (10.8-108 J/day). The number and the total area of mineralized bone modules that had developed in the culture dish on day 21 were evaluated. DNA content, alkaline phosphatase (ALP) activity and the amount of extra-cellular collagen were also measured. Calcium and phosphorus in bone nodules were examined with an X-ray microanalyzer. Laser irradiation significantly increased the number and the total area of bone nodules in a dose-dependent manner. Cell proliferation and ALP activity in the irradiation group were higher in the early and middle culture periods, while the collagen content was higher in the middle an late periods compared with the control. Calcium and phosphorus were both higher in the irradiation group. These findings indicate that laser irradiation may play a principal role in stimulating differentiation of osteoblasts during the early stage of the culture, resulting in increased bone formation through acceleration of bone nodule maturation.

Ozawa, Yasuhito; Shimizu, Noriyoshi; Mishima, Hiroyuki; Kariya, Genichiro; Yamaguchi, Masaru; Takiguchi, Hisashi; Iwasawa, Tadamasa; Abiko, Yoshimitsu

1995-04-01

62

Soy isoflavones attenuate bone loss in early postmenopausal Chinese women  

Microsoft Academic Search

Background  Previous studies show that daily doses of 40–99 mg soy isoflavones produce inconsistent effects on preventing estrogen-related\\u000a bone loss in postmenopausal women.\\u000a \\u000a \\u000a \\u000a Aim of the study  To examined the bone-sparing effect of isoflavones at a higher dose in early Chinese postmenopausal women.\\u000a \\u000a \\u000a \\u000a Methods  A total of 90 eligible women aged 45–60 years were randomly assigned to three treatment groups (30 subjects\\/group) with daily\\u000a dosages

Yan-Bin Ye; Xing-Yi Tang; Marian A. Verbruggen; Yi-Xiang Su

2006-01-01

63

FOXOs attenuate bone formation by suppressing Wnt signaling  

PubMed Central

Wnt/?-catenin/TCF signaling stimulates bone formation and suppresses adipogenesis. The hallmarks of skeletal involution with age, on the other hand, are decreased bone formation and increased bone marrow adiposity. These changes are associated with increased oxidative stress and decreased growth factor production, which activate members of the FOXO family of transcription factors. FOXOs in turn attenuate Wnt/?-catenin signaling by diverting ?-catenin from TCF- to FOXO-mediated transcription. We show herein that mice lacking Foxo1, -3, and -4 in bipotential progenitors of osteoblast and adipocytes (expressing Osterix1) exhibited increased osteoblast number and high bone mass that was maintained in old age as well as decreased adiposity in the aged bone marrow. The increased bone mass in the Foxo-deficient mice was accounted for by increased proliferation of osteoprogenitor cells and bone formation resulting from upregulation of Wnt/?-catenin signaling and cyclin D1 expression, but not changes in redox balance. Consistent with this mechanism, ?-catenin deletion in Foxo null cells abrogated both the increased cyclin D1 expression and proliferation. The elucidation of a restraining effect of FOXOs on Wnt signaling in bipotential progenitors suggests that FOXO activation by accumulation of age-associated cellular stressors may be a seminal pathogenetic mechanism in the development of involutional osteoporosis.

Iyer, Srividhya; Ambrogini, Elena; Bartell, Shoshana M.; Han, Li; Roberson, Paula K.; de Cabo, Rafael; Jilka, Robert L.; Weinstein, Robert S.; O'Brien, Charles A.; Manolagas, Stavros C.; Almeida, Maria

2013-01-01

64

Changes in homeobox-containing gene expression during ectopic bone formation induced by bone morphogenetic protein.  

PubMed

Expression of homeobox genes in relation to ectopic bone formation induced by bone morphogenetic protein (BMP) was investigated. Oligonucleotide primers corresponding to highly conserved regions of Hox cluster and Msx genes were designed to detect homeobox sequences by means of the polymerase chain reaction (PCR). Nine rat homologues of Hox cluster genes and two Msx genes were discovered in the BMP-implanted tissue, at earlier stage and later cartilage and bone formation stage, respectively. The PCR study provided evidence of dynamic changes in BMP-induced homeobox gene expression. PMID:7911662

Iimura, T; Oida, S; Takeda, K; Maruoka, Y; Sasaki, S

1994-06-15

65

Alveolar bone formation at dental implant dehiscence defects following guided bone regeneration and xenogeneic freeze-dried demineralized bone matrix.  

PubMed

The present study evaluated rate and extent of alveolar bone formation in dental implant dehiscence defects following guided bone regeneration (GBR) and implantation of xenogeneic freeze-dried demineralized bone matrix (xDBM). A total of 16 titanium plasma-sprayed (TPS) and 16 hydroxyapatite-coated (HA) titanium cylinder implants were inserted in 4 mongrel dogs following extraction of the mandibular premolar teeth. Four implant sites per jaw quadrant (2 TPS and 2 HA implant sites) were prepared into extraction sockets in each dog. Buccal alveolar bone was removed to create 3 x 5 mm dehiscence defects. Two jaw quadrants in separate animals received GBR, GBR + xDBM, xDBM (control), or gingival flap surgery alone (GFS; control). Thus, four conditions were available for each implant type (TPS or HA): GBR, GBR + xDBM; xDBM and GFS. The animals received fluorescent bone labels to allow observations of rate and extent of bone formation. Animals were sacrificed at 12 weeks postsurgery and block sections were harvested for histologic analysis. There were no apparent histologic differences between TPS and HA implant defects. GBR and GBR + xDBM resulted in almost complete bone closure of the dental implant dehiscence defect. Rate of bone formation appeared higher following GBR alone. Extent of bone formation appeared somewhat greater following GBR + xDBM; however, delayed. xDBM alone did not adequately resolve the bony defect. In conclusion, GBR results in rapid, clinically relevant bone closure of dental implant dehiscence defects. Adjunctive implantation of xDBM does not appear to significantly improve the healing response in the model used. PMID:11429943

Cho, K S; Choi, S H; Han, K H; Chai, J K; Wikesjö, U M; Kim, C K

1998-12-01

66

Hepcidin1 knockout mice display defects in bone microarchitecture and changes of bone formation markers.  

PubMed

Iron accumulation is a risk factor of osteoporosis; mechanisms leading to iron-related bone loss are not fully determined. We sought to better understand the effect of chronic iron accumulation on bone over the life span in a mouse model. Hepcidin1 knockout (Hepc1(-/-)) male mice and their littermate control wild type (WT) mice at 7 months old were used in this study. Serum iron and ferritin as well as iron contents in liver and femur were significantly increased in Hepc1(-/-) mice compared to WT mice. We found that Hepc1(-/-) mice had a phenotype of low bone mass and alteration of the bone microarchitecture, most likely caused by a decreased osteoblastic activity. Cell culture studies indicated that chronic iron accumulation decreased bone formation, probably by affecting bone morphogenetic protein signaling. PMID:24652331

Shen, Guang Si; Yang, Qing; Jian, Jing Long; Zhao, Guo Yang; Liu, Lu Lin; Wang, Xiao; Zhang, Wen; Huang, Xi; Xu, You Jia

2014-06-01

67

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

68

Cadherins and Wnt signalling: a functional link controlling bone formation  

PubMed Central

Cadherins are calcium-dependent cell adhesion molecules that have a major role in morphogenesis and tissue formation. In bone, cadherins control osteoblast differentiation by mediating cell–cell adhesion and signals that promote phenotypic osteoblast gene expression. Furthermore, cadherins can interact with Wnt signalling to modulate osteoblastogenesis. One mechanism involves the interaction of N-cadherin with ?-catenin at the cell membrane, resulting in ?-catenin sequestration, reduction of the cytosolic ?-catenin pool and inhibition of Wnt signalling. In addition to modulating the ?-catenin pool, N-cadherin can regulate osteoblasts by interacting with the Wnt coreceptors LRP5 or LRP6. We showed that the functional interaction between N-cadherin and LRP5/6 in osteoblasts promotes ?-catenin degradation and reduces canonical Wnt signalling. This crosstalk between N-cadherin and Wnt signalling has a negative impact on osteoblast proliferation, differentiation and survival, independently of cell–cell adhesion, which results in decreased bone formation and delayed bone accrual in mice. The identification of this crosstalk between N-cadherin and Wnt signalling may have therapeutic implications, as a disruption of the N-cadherin–LRP5/6 interaction using a competitor peptide can increase Wnt/?-catenin signalling without affecting cell–cell adhesion, and this effect results in increased osteoblastogenesis and bone tissue formation in vivo. In this review, we summarize our current knowledge of the key crosstalks between cadherins and Wnt signalling that impact osteoblast function, bone formation and bone mass, and the possible therapeutic implications of such interactions for promoting osteoblastogenesis, bone formation and bone mass.

Marie, Pierre J; Hay, Eric

2013-01-01

69

Soy isoflavone intake inhibits bone resorption and stimulates bone formation in menopausal women: meta-analysis of randomized controlled trials  

Microsoft Academic Search

Objective:To clarify the effects of isoflavone intake on bone resorption and bone formation.Methods:We identified randomized controlled trials related to urinary deoxypyridinoline (Dpyr, a bone resorption marker) and serum bone-specific alkaline phosphatase (BAP, a bone formation marker) listed on MEDLINE (January 1966–April 2006), the Cochrane Controlled Trials Register, EMBASE (1985–January 2006), Science Citation Index and PUBMED (updated till April 2006).Results:Nine studies

D-F Ma; L-Q Qin; P-Y Wang; R Katoh

2008-01-01

70

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

71

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.

WANG, LIN; PARK, PAUL; LA MARCA, FRANK; THAN, KHOI; RAHMAN, SHAYAN; LIN, CHIA-YING

72

Are glucocorticoids harmful to bone in early rheumatoid arthritis?  

PubMed

In the past, patients with rheumatoid arthritis (RA) were treated with monotherapy with conventional drugs, such as sulfasalazine, methotrexate, and intramuscular gold, which often leads to persistent arthritis, loss of functional capacity, and decreased quality of life. Both active RA and the use of high-dose glucocorticoids (GCs) are associated with generalized bone loss and fractures, but it is well known that GCs have a strong immunosuppressive effect. With the introduction of tumor necrosis factor (TNF-?)-blockers and other biologics, clinical remission is a realistic target in approximately half of the early RA patients; the same seems to be true for the use of methotrexate with chronic low-dose or initially high-dose GCs. With the use of a treat-to-target strategy focusing on clinical remission or low disease activity in early RA patients, the negative effects of systemic inflammation on bone can be arrested, and both local bone loss (in the joints) and generalized bone loss at the spine and hips can be prevented. PMID:24739059

Lems, Willem F

2014-05-01

73

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

PubMed Central

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

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

2010-01-01

74

Familial early onset sarcoidosis with bone cysts and erosions.  

PubMed

Early onset sarcoidosis is a granulomatous disease which is characterized by synovitis, polyarthritis, skin and eye involvement. We report the skeletal features of one patient with a family history and clinical symptoms suggestive of early onset sarcoidosis (EOS) which was confirmed by skin biopsy. Radiographs reveal postarthritic deformities of the MCP joints, contractures, a coarsened trabecular pattern at the PIP joints and small bone cysts resembling osteitis cystoides multiplex. Similar lesions were described in radiographs of the older sister and an uncle of our patient. This is the first report demonstrating bone cysts and erosions which could be a diagnostic feature in this rare disease and may help to differentiate other rheumatoid disorders. PMID:17492440

Blank, Norbert; Max, Regina; Autschbach, Frank; Libicher, Martin; Lorenz, Hanns-Martin

2007-09-01

75

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

PubMed Central

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

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

2008-01-01

76

Early Growth Response Gene 1 Regulates Bone Properties in Mice  

Microsoft Academic Search

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

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

2011-01-01

77

Prevention of bone metastases and management of bone health in early breast cancer  

PubMed Central

Treatment options for women with early-stage breast cancer have never been better, and the addition of bisphosphonates to adjuvant therapy is a valuable new tool capable of substantially improving clinical outcomes for these women. Several recent studies demonstrated that the anticancer activity of bisphosphonates is not limited to bone, and can translate into a reduction in disease recurrence, including reductions in locoregional and distant metastases. In addition, bisphosphonates maintain bone health during adjuvant therapy; this may be especially important for women who are at high risk for fracture.

2010-01-01

78

Short-term aluminum administration in the rat. Effects on bone formation and relationship to renal osteomalacia.  

PubMed Central

Aluminum may be pathogenic in the osteomalacia observed in some patients receiving hemodialysis. To study the early effects of Al on bone growth, bone formation, mineralization, and resorption were measured during short-term Al exposure in the tibial cortex of pair-fed control (C, n = 10), aluminum-treated (AL, n = 9), subtotally nephrectomized control (NX-C, n = 7), and subtotally nephrectomized aluminum-treated (NX-AL, n = 8) rats using double tetracycline labeling of bone. Animals received 2 mg/d of elemental Al intraperitoneally for 5 d/wk over 4 wk. Total bone and matrix (osteoid) formation, periosteal bone and matrix formation, and periosteal bone and matrix apposition fell by 20% in AL from C, P less than 0.05 for all values, and by 40% in NX-AL from NX-C, P less than 0.01 for all values. Moreover, each measurement was significantly less in NX-AL than in AL, P less than 0.05 for all values. Osteoid width did not increase following aluminum administration in either AL or NX-AL. Resorption surface increased from control values in both AL and NX-AL; also, resorptive activity at the endosteum was greater in NX-AL than in NX-C, P less than 0.05. Thus, aluminum impairs new bone and matrix formation but does not cause classic osteomalacia in the cortical bone of rats whether renal function is normal or reduced. These findings may represent either a different response to aluminum administration in cortical bone as contrasted to trabecular bone or an early phase in the development of osteomalacia. Aluminum may increase bone resorption and contribute to osteopenia in clinical states associated with aluminum accumulation in bone.

Goodman, W G; Gilligan, J; Horst, R

1984-01-01

79

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.

2014-01-01

80

The glycosylation profile of osteoadherin alters during endochondral bone formation.  

PubMed

Endochondral bone formation involves the dynamic interplay between the cells and their extracellular environment to facilitate the deposition of a calcified matrix. Numerous molecules are involved within this process, including collagens and non-collagenous proteins, and their post-translational modifications have been shown to effect their biomolecular interactions. Osteoadherin (OSAD), a keratin sulfate (KS)-substituted small leucine-rich proteoglycan has been isolated from mineralized tissues and is considered to be a mineralized tissue-specific protein. However, to date, information is limited concerning the dynamic expression and role of this proteoglycan during bone formation and the biomineralization process. The current study aimed to examine the dynamic expression of this protein throughout mouse metatarsal long bone development, from the cartilage anlagen (E15) to the fully formed bone (Adult). Using quantitative gene expression analysis we observed that OSAD was produced with the onset of mineralization and the formation of the ossification center. This finding was reflected in the localization studies, using both light and electron microscopy, and showed that initial OSAD localization was restricted to the endosteal surfaces of the diaphysis and forming metaphysis. Furthermore, we analyzed protein extracts, both mineral and non-mineral associated fractions, and showed that OSAD was substituted with varying patterns of glycosylation during bone development. Sequential enzymatic digestions of the non-mineral bound protein extracts demonstrated that OSAD lacked any KS chains throughout all development stages. Whereas, in the mineral bound fractions, with long bone maturation the substitution with KS became more apparent with development. Therefore, it can be concluded that different pools of OSAD are produced during endochondral bone formation and these may have specific roles in directing the mineralization process. PMID:23337037

Sugars, Rachael V; Olsson, Marie-Louise; Marchner, Sara; Hultenby, Kjell; Wendel, Mikael

2013-04-01

81

Ultraviolet light-irradiated photocrosslinkable chitosan hydrogel to prevent bone formation in both rat skull and fibula bone defects.  

PubMed

In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to suppress excessive bone formation, such as ectopic bone formation, ossifying myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinked chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of bone defect. Rat calvarium and fibula were surgically injured and PCH was implanted into the resultant bone defects. The PCH implants significantly prevented bone formation in the bone defects during the 4 and 8 week observation periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory cells were formed by day 7, completely filling the bone defects. In addition to these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA, both markers of bone formation, was lower in the PCH-treated defects than in the controls. In contrast, collagen type 1?2 and ?-smooth muscle actin (?-SMA) mRNA levels were significantly higher in the PCH-treated defects after 1 week. PCH stimulated the formation of fibrous tissue in bone defects while inhibiting bone formation. Thus, PCH might be a promising new therapeutic biomaterial for the prevention of bone formation in orthopaedic surgery. PMID:22408001

Tsuda, Yoshifumi; Hattori, Hidemi; Tanaka, Yoshihiro; Ishihara, Masayuki; Kishimoto, Satoko; Amako, Masatoshi; Arino, Hiroshi; Nemoto, Koichi

2013-09-01

82

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

PubMed Central

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.

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

2011-01-01

83

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

84

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.

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

85

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.

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

2010-01-01

86

The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling  

Microsoft Academic Search

The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling.BackgroundLoss of bone mass after transplantation begins in the early periods after transplantations and may persist for several years, even in patients with normal renal function. While the pathogenesis of these abnormalities is still unclear, several studies suggest that preexisting bone disease, glucocorticoid therapy, and alterations

Eudocia Rojas; Raul G Carlini; Paul Clesca; Anabella Arminio; Orlando Suniaga; Karen De Elguezabal; José R Weisinger; Keith A Hruska

2003-01-01

87

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.

2013-01-01

88

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

89

Effects Of Stress On Bone-Formation Markers In Rats  

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

90

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

Microsoft Academic Search

Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and

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

2008-01-01

91

Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling.  

PubMed

Cardiotrophin (CT-1) signals through gp130 and the LIF receptor (LIFR) and plays a major role in cardiac, neurological, and liver biology. We report here that CT-1 is also expressed within bone in osteoclasts and that CT-1 is capable of increasing osteoblast activity and mineralization both in vitro and in vivo. Furthermore, CT-1 stimulated CAAT/enhancer-binding protein-delta (C/EBP delta) expression and runt-related transcription factor 2 (runx2) activation. In neonate CT-1(-/-) mice, we detected low bone mass associated with reduced osteoblasts and many large osteoclasts, but increased cartilage remnants within the bone, suggesting impaired resorption. Cultured bone marrow (BM) from CT-1(-/-) mice generated many oversized osteoclasts and mineralized poorly compared with wildtype BM. As the CT-1(-/-) mice aged, the reduced osteoblast surface (ObS/BS) was no longer detected, but impaired bone resorption continued resulting in an osteopetrotic phenotype in adult bone. CT-1 may now be classed as an essential osteoclast-derived stimulus of both bone formation and resorption. PMID:18665789

Walker, Emma C; McGregor, Narelle E; Poulton, Ingrid J; Pompolo, Sueli; Allan, Elizabeth H; Quinn, Julian M W; Gillespie, Matthew T; Martin, T John; Sims, Natalie A

2008-12-01

92

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

93

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

94

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

PubMed Central

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

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

2013-01-01

95

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

SciTech Connect

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

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

1986-12-01

96

[Osteoplastic pneumopathy (disseminated bone formation in the lung)].  

PubMed

8 cases of pneumophathia osteoplastica (ppo) of branching type observed at patients having no vascular deformities and one case of a focal ppo at a patient with mitral stenosis are reported. Pathogenesis of the ppo of branching type in the majority of cases could not be clarified since the process appeared to be in the phase of definitive bone formation. Nevertheless in one of the cases in a septum of Y shape in addition to collagen fibres ending in bone tissue numerous elastic fibres have also been revealed. This fact, considering the presence of a normal bronchus in the area seems to evidence vascular origin of the lesion. The latter hypothesis could be verified by the bone-formation in the media of a vessel wall in another case. Further, in a case of primary chronic polyarthritis with ppo, bone-formation could be seen in the perivascular lung tissue with necrotizing pulmonal arteritis. Considering this finding the possibility of the primary role of necrotizing pulmonal arthritis in the pathogenesis of ppo have to be taken into account. Ppo should be classified as one of the alveolocapillary block syndromes. In some cases it may have clinico-pathological significance. It may lead to bronchietasis, emphyseme or cor pulmonale chronicum. PMID:6790943

Baranyay, F

1981-01-01

97

BONE FORMATION INDUCED IN MOUSE THIGH BY CULTURED HUMAN CELLS  

PubMed Central

Cultured FL human amnion cells injected intramuscularly into cortisone-conditioned mice proliferate to form discrete nodules which become surrounded by fibroblasts. Within 12 days, fibroblastic zones differentiate into cartilage which calcifies to form bone. Experiments were conducted to test the hypothesis that FL cells behave as an inductor of bone formation. In the electron microscope, FL cells were readily distinguished from surrounding fibroblasts. Transitional forms between the two cell types were not recognized. Stains for acid mucopolysaccharides emphasized the sharp boundary between metachromatic fibroblastic and cartilaginous zones and nonmetachromatic FL cells. 35S was taken up preferentially by fibroblasts and chondrocytes and then deposited extracellularly in a manner suggesting active secretion of sulfated mucopolysaccharides. FL cells showed negligible 35S utilization and secretion. FL cells, labeled in vitro with thymidine-3H, were injected and followed radioautographically, during bone formation. Nuclear label of injected FL cells did not appear in adjacent fibroblasts in quantities sufficient to indicate origin of the latter from FL cells. The minimal fibroblast nuclear labeling seen may represent reutilization of label from necrotic FL cells. It is suggested that FL cells injected into the mouse thigh induced cartilage and bone formation by host fibroblasts.

Anderson, H. Clarke; Coulter, P. R.

1967-01-01

98

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

PubMed Central

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

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

2013-01-01

99

Craniosynostosis-associated Fgfr2(C342Y) mutant bone marrow stromal cells exhibit cell autonomous abnormalities in osteoblast differentiation and bone formation.  

PubMed

We recently reported that cranial bones of Fgfr2(C342Y/+) craniosynostotic mice are diminished in density when compared to those of wild type mice, and that cranial bone cells isolated from the mutant mice exhibit inhibited late stage osteoblast differentiation. To provide further support for the idea that craniosynostosis-associated Fgfr mutations lead to cell autonomous defects in osteoblast differentiation and mineralized tissue formation, here we tested bone marrow stromal cells isolated from Fgfr2(C342Y/+) mice for their ability to differentiate into osteoblasts. Additionally, to determine if the low bone mass phenotype of Crouzon syndrome includes the appendicular skeleton, long bones were assessed by micro CT. Fgfr2(C342Y/+) cells showed increased osteoblastic gene expression during early osteoblastic differentiation but decreased expression of alkaline phosphatase mRNA and enzyme activity, and decreased mineralization during later stages of differentiation, when cultured under 2D in vitro conditions. Cells isolated from Fgfr2(C342Y/+) mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of Fgfr2(C342Y/+) mice. These results demonstrate that marrow stromal cells of Fgfr2(C342Y/+) mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the Fgfr2(C342Y) mutation influences both the axial and appendicular skeletons. PMID:23762837

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

2013-01-01

100

Low-level mechanical vibrations can influence bone resorption and bone formation in the growing skeleton  

Microsoft Academic Search

Short durations of extremely small magnitude, high-frequency, mechanical stimuli can promote anabolic activity in the adult skeleton. Here, it is determined if such signals can influence trabecular and cortical formative and resorptive activity in the growing skeleton, if the newly formed bone is of high quality, and if the insertion of rest periods during the loading phase would enhance the

Liqin Xie; Jeffrey M. Jacobson; Edna S. Choi; Bhavin Busa; Leah Rae Donahue; Lisa M. Miller; Clinton T. Rubin; Stefan Judex

2006-01-01

101

Profilin1 Regulates Sternum Development and Endochondral Bone Formation  

PubMed Central

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

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

2012-01-01

102

Porphyromonas gingivalis invades osteoblasts and inhibits bone formation.  

PubMed

Porphyromonas gingivalis is etiologically associated with adult periodontitis, but it is unclear how P. gingivalis long-term interactions with bone cells contribute to this disease. This study investigates P. gingivalis interactions with osteoblasts over an extended time course. A primary mouse calvarial osteoblast culture was established and inoculated with P. gingivalis 33277 repeatedly every other day for up to four weeks. Invasion of osteoblasts by P. gingivalis, and the resulting effects on the proliferation, differentiation, and mineralization of osteoblasts were evaluated. P. gingivalis was found to invade osteoblasts in a dose-dependent manner, and repetitive inoculation increased the percentage of osteoblasts with internalized P. gingivalis. P. gingivalis did not affect osteoblast proliferation, but inhibited their differentiation and mineralization, partially via an inhibition of the differentiation regulatory transcription factors Cbfa-1 and osterix. In conclusion, P. gingivalis invades osteoblasts and inhibits bone formation, which likely contributes to alveolar bone loss in chronic periodontitis. PMID:20538069

Zhang, Wenjian; Swearingen, Elizabeth B; Ju, Jun; Rigney, Todd; Tribble, Gena D

2010-10-01

103

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

PubMed

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

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

2013-07-01

104

Postablation bone marrow regeneration: An in vivo model to study differential regulation of bone formation and resorption  

Microsoft Academic Search

The postablation bone marrow regeneration model is an in vivo paradigm of synchronous bone formation and resorption restricted to a defined reference anatomical location. The blood clot that fills the medullary cavity immediately after removal is organized by replacement with primary cancellous bone. At the peak of the osteogenic phase almost the entire medullary cavity is filled with the trabecular

I. A. Bab

1995-01-01

105

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

106

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.

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

2012-01-01

107

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

PubMed

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

108

Bone Formation During Distraction Osteogenesis Is Dependent on Both VEGFR1 and VEGFR2 Signaling  

PubMed Central

Introduction Distraction osteogenesis (DO) is characterized by the induction of highly vascularized new bone formation through an intramembranous process largely devoid of the formation of cartilage. Materials and Methods To test the hypothesis that DO is strictly dependent on vascualrization, we inhibited vascular endothelial growth factor (VEGF) activity by antibody blockade of both receptors VEGFR1 (Flt-1) and VEGFR2 (Flk-1) or only VEGFR2 (Flk-1) in a previously developed murine tibia DO model. During normal DO, VEGFR1 (Flt-1), VEGFR2 (Flk-1), VEGFR3 (Flt4) and all four VEGF ligand (A, B, C, and D) mRNAs are induced. Results The expression of mRNA for the receptors generally paralleled those of the ligands during the period of active distraction. Bone formation, as assessed by ?CT, showed a significant decrease with the double antibody treatment and a smaller decrease with single antibody treatment. Vessel volume, number, and connectivity showed progressive and significant inhibition in all of these of parameters between the single and double antibody blockade. Molecular analysis showed significant inhibition in skeletal cell development with the single and double antibody blockade of both VEGFR1 and 2. Interestingly, the single antibody treatment led to selective early development of chondrogenesis, whereas the double antibody treatment led to a failure of both osteogenesis and chondrogenesis. Conclusions Both VEGFR1 and VEGFR2 are functionally essential in blood vessel and bone formation during DO and are needed to promote osteogenic over chondrogenic lineage progression.

Jacobsen, Kimberly A; Al-Aql, Zainab S; Wan, Chao; Fitch, Jennifer L; Stapleton, Stephanie N; Mason, Zachary D; Cole, Robert M; Gilbert, Shawn R; Clemens, Thomas L; Morgan, Elise F; Einhorn, Thomas A; Gerstenfeld, Louis C

2008-01-01

109

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

PubMed Central

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

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

2013-01-01

110

Soy protein consumption and bone mass in early postmenopausal Chinese women  

Microsoft Academic Search

Recent interest has been shown in the potential beneficial effects of phytoestrogens on bone health. As the early years of menopause are a period of rapid bone loss, and the risk for osteoporosis increases substantially, the habitual intake of soy protein and isoflavones may play a role in the retardation of bone loss. This paper reports the results of the

Suzanne C. Ho; Jean Woo; Silvia Lam; Yuming Chen; Aprille Sham; Joseph Lau

2003-01-01

111

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

Microsoft Academic Search

OBJECTIVEThis study investigated determinants of bone and blood lead concentrations in 430 lactating Mexican women during the early postpartum period and the contribution of bone lead to blood lead.METHODSMaternal venous lead was measured at delivery and postpartum, and bone lead concentrations, measured with in vivo K-xray fluorescence, were measured post partum. Data on environmental exposure, demographic characteristics, and maternal factors

Mary Jean Brown; Howard Hu; Teresa Gonzales-Cossio; Karen E Peterson; Luz-Helena Sanin; Maria de Luz Kageyama; Eduardo Palazuelos; Antonio Aro; Lourdes Schnaas; Mauricio Hernandez-Avila

2000-01-01

112

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.

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

2013-01-01

113

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

Microsoft Academic Search

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

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

114

Effect of pulsed electromagnetic fields on bone formation and bone loss during limb lengthening  

Microsoft Academic Search

We examined the effect of pulsed electromagnetic fields (PEMFs) on bone formation and disuse osteoporosis sustained during limb lengthening in a double-blind study. Seven males (mean age 13 years, range 11–19 years) and six females (mean age 12 years, range 9–19 years) were randomly allocated to receive either an active or an inactive PEMF coil. Limb lengthening was performed by

K. S. Eyres; M. Saleh; J. A. Kanis

1996-01-01

115

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

Microsoft Academic Search

BACKGROUND: Statin can induce the gene expression of bone morphogenetic protein-2. Red yeast rice (RYR, Hongqu), i.e. rice fermented with Monascus purpureus, contains a natural form of statin. This study demonstrates the effects of RYR extract on bone formation. METHODS: Bone defects were created in the parietal bones of two New Zealand white rabbits. In the test animal, two defects

Ricky WK Wong; Bakr Rabie

2008-01-01

116

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

117

The stimulation of bone formation in vitro by therapeutic ultrasound.  

PubMed

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/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min, significantly stimulates bone formation (i.e., the synthesis of collagen and NCP) (p < 0.001 and p < 0.01). However, pulsed ultrasound at higher doses (1.0-2.0 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min) significantly inhibited the synthesis of both collagen and NCP (p < 0.05). The temperature measurements showed a maximum rise of 1.8 degrees C [at 2.0 W/cm2 (SATA)] and no detected rise at 0.1 W/cm2 (SATA), suggesting that the effects in this study were primarily nonthermal. These results may reflect the healing effect of US on fractures and osteoradionecrosis and reinforces the use of low intensity US regimens [0.1 W/cm2 (SATA)] in clinical practice. PMID:9372573

Reher, P; Elbeshir el-NI; Harvey, W; Meghji, S; Harris, M

1997-01-01

118

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.

2012-01-01

119

Histopathological Assessment of Fibrosis and New Bone Formation in Implanted Human Temporal Bones Using 3D-Reconstruction  

PubMed Central

OBJECTIVE To evaluate new bone formation and fibrosis in implanted human temporal bones and relate that to neurosensory elements preservation. STUDY DESIGN Human temporal bone histopathology study. SETTING Temporal bone laboratory. SUBJECTS AND METHODS Ten human temporal bones from eight patients with multichannel cochlear implants and one single-electrode implant were examined under light microscopy and reconstructed using AMIRA 4.1 3D reconstruction software. Volumes of new bone formation, fibrosis and patent area were calculated in each bone. RESULTS The amount of fibrosis and new bone formation postimplantation varied among bones. There were no statistically significant relationships between age at implantation or duration of implantation and the overall amount of new tissue in the implanted ear. There was a relationship between total amount of new tissue and preservation of neurosensory elements only in Segment I of the cochlea (Rho=?.75, p?.013). Most of the new tissue was located in segments I and II, while segment III had little to no new tissue formation and segment IV was clear in all of the subjects. CONCLUSION New tissue formation postimplantation was related to preservation of neurosensory elements primarily in segment I of the cochlea. In an era of hearing preservation surgery and hybrid cochlear implants, soft surgical techniques are advocated as a means to decrease surgical trauma.

Fayad, Jose N.; Makarem, Andres O.; Linthicum, Fred H.

2009-01-01

120

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

PubMed Central

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

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

2011-01-01

121

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

Microsoft Academic Search

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

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

2005-01-01

122

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.

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

2008-01-01

123

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

NASA Astrophysics Data System (ADS)

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

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

124

Vaccination with DKK1-derived Peptides Promotes Bone Formation and Bone Mass in an Aged Mouse Osteoporosis Model.  

PubMed

The investigation of agents for the treatment of osteoporosis has been a long-standing effort. The Wnt pathway plays an important role in bone formation and regeneration, and expression of Wnt pathway inhibitors, Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of DKK1 leads to substantially increased bone mass in genetically manipulated animals. DKK1-derived peptides (DDPs) were added to BMP2-stimulated MC3T3-E1 preosteoblastic cells in vitro to evaluate inhibitory activity of DDPs in MC3T3-E1 cell differentiation. Study was extended in vivo on old female mice to show whether or not inhibition of endogenous DKK1 biological activity using DDPs vaccination approach leads to increase of bone formation, bone density, and improvement of bone microstructure. We reported that synthetic DDPs were able to reduce alkaline phosphatase activity, prevent mineralization and inhibit the differentiation of MC3T3-E1 cells in vitro. Furthermore, vaccination with these DDPs in aged female mice 4 times for a total period of 22 weeks promoted bone mass and bone microstructure. 3D microCT and histomorphometric analysis showed that there were significant increase in bone mineral densities, improvement of bone microstructure and promotion of bone formation in the vaccinated mice, especially in the mice vaccinated with DDP-A and DDP-C. Histological and scanning electron microscopy image analysis also indicated that vaccination increased trabecular bone mass and significantly decreased fragmentation of bone fibers. Taken together, these preclinical results suggest that vaccination with DDPs represents a promising new therapeutic approach for the treatment of bone-related disorders, such as osteoporosis. PMID:24907907

Wu, Qiong; Li, Rui-Shu; Zhao, Yue; Wang, Zhi-Xia; Tang, Yan-Chun; Zhang, Jing; Liu, Jian-Ning; Tan, Xiang-Yang

2014-08-01

125

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

PubMed

In this work, we focus on the in vitro and in vivo response of composite scaffolds obtained by incorporating Mg,CO3 -doped hydroxyapatite (HA) particles in poly(?-caprolactone) (PCL) porous matrices. After a complete analysis of chemical and physical properties of synthesized particles (i.e. SEM/EDS, DSC, XRD and FTIR), we demonstrate that the Mg,CO3 doping influences the surface wettability with implications upon cell-material interaction and new bone formation mechanisms. In particular, ion substitution in apatite crystals positively influences the early in vitro cellular response of human mesenchymal stem cells (hMSCs), i.e. adhesion and proliferation, and promotes an extensive mineralization of the scaffold in osteogenic medium, thus conforming to a more faithful reproduction of the native bone environment than undoped HA particles, used as control in PCL matrices. Furthermore, we demonstrate that Mg,CO3 -doped HA in PCL scaffolds support the in vivo cellular response by inducing neo-bone formation as early as 2?months post-implantation, and abundant mature bone tissue at the sixth month, with a lamellar structure and completely formed bone marrow. Together, these results indicate that Mg(2+) and CO3 (2-) ion substitution in HA particles enhances the scaffold properties, providing the right chemical signals to combine with morphological requirements (i.e. pore size, shape and interconnectivity) to drive osteogenic response in scaffold-aided bone regeneration. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22730225

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

2014-04-01

126

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

PubMed Central

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

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

1994-01-01

127

Parecoxib impairs early metaphyseal bone healing in rats  

Microsoft Academic Search

Introduction\\u000a   Cox2 inhibitors decrease prostaglandin production and therefore influence bone healing especially in unstable long bone models. It is unclear to what extent implant fixation in stable metaphyseal bone is impaired.\\u000a Method\\u000a   Male rats numbering 30 and female rats numbering 40 received a stainless steel screw in the metaphyseal bone of the proximal tibia. Half of the rats were treated

Andreas Meunier; Per Aspenberg

2006-01-01

128

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

Microsoft Academic Search

BACKGROUND: Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients

Carsten Müller; Corinna C Winter; Dieter Rosenbaum; Joachim Boos; Georg Gosheger; Jendrik Hardes; Volker Vieth

2010-01-01

129

Local delivery of rolipram, a phosphodiesterase-4-specific inhibitor, augments bone morphogenetic protein-induced bone formation  

Microsoft Academic Search

Recombinant human bone morphogenetic protein (rhBMP) is a promising therapeutic cytokine for the induction of bone formation,\\u000a but a weak response in humans remains a major hurdle in its therapeutic application. We have previously reported an rhBMP-2-induced\\u000a increase in the bone mass of mice receiving systemic rolipram, a specific inhibitor of phosphodiesterase-4. To overcome the\\u000a side effects of systemic administration

Yoshio Tokuhara; Shigeyuki Wakitani; Yuuki Imai; Chizumi Nomura; Masatoshi Hoshino; Koichi Yano; Susumu Taguchi; Mitsunari Kim; Yoshinori Kadoya; Kunio Takaoka

2010-01-01

130

A prostanoid receptor EP4 agonist enhances ectopic bone formation induced by recombinant human bone morphogenetic protein-2  

Microsoft Academic Search

The anabolic effects of prostaglandin E2 on bone are effected through the activation of EP4, a G protein-coupled receptor. In the present study, we examined the effects of a prostanoid receptor-selective agonist (ONO-4819) in an experimental system of ectopic bone formation using recombinant human bone morphogenetic protein-2 (rhBMP-2). Collagen pellets containing rhBMP-2 were implanted onto the back muscles of mice

Ryuichi Sasaoka; Hidetomi Terai; Hiromitsu Toyoda; Yuuki Imai; Ryo Sugama; Kunio Takaoka

2004-01-01

131

MRI detection of early bone metastases in B16 mouse melanoma models  

PubMed Central

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

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

2009-01-01

132

An acute intake of phosphate increases parathyroid hormone secretion and inhibits bone formation in young women.  

PubMed

We studied the effects of a single oral phosphate (Pi) dose as well as those of three consecutive oral phosphate doses on calcium and bone metabolism. In the first part of the study (P1 study) 10 female volunteers were given orally 1500 mg of Pi in water, as a single dose, or plain water in randomized order at two different sessions. In the second part of the study (P3 study), 10 female volunteers were given orally 1500 mg of Pi, as three separate 500 mg doses in water, or plain water in randomized order. Calcium and bone metabolism was monitored for 24 h by measuring the concentrations of serum ionized calcium (S-iCa), urinary calcium, serum phosphate (S-P), urinary P, serum intact parathyroid hormone (PTH), serum carboxy-terminal propeptide of type I collagen (PICP), serum osteocalcin (BGP), serum carboxy-terminal telopeptide of type I collagen (ICTP), urine deoxypyridinoline (DPD) and bone-specific alkaline phosphatase activity (B-ALP). The S-P increased (p = 0.00005 and p = 0.0005, in the P1 and P3 studies, respectively), the S-iCa concentration declined significantly only in the P1 study (p = 0.0014), the urinary calcium excretion decreased (p = 0.02 and 0.013, in the P1 and P3 studies, respectively), and the PTH concentration rose (p = 0.0083 and p = 0.014, in the P1 and P3 studies, respectively) during the phosphate experiment as compared with the control session. Of the three markers of bone formation studied, PICP declined in the P1 study (p = 0.04), and B-ALP declined in both parts of the study (p = 0.027, p = 0.026, in the P1 and P3 studies, respectively) after phosphate administration, whereas there was no significant change in BGP in either of the studies. The markers of bone resorption, ICTP and DPD, were unaffected by the phosphate load in both studies. In conclusion, acute ingestion of phosphate leads to an increase in S-P, a decrease in S-iCa, and an increase in intact PTH secretion. Our results indicate that these events may lead to an acute inactivation of the early phases of bone formation. In this setting, there was no indication of enhanced bone resorption despite the increase in PTH secretion, which could be due to the combined effect of phosphate and PTH on bone resorption. PMID:8970892

Kärkkäinen, M; Lamberg-Allardt, C

1996-12-01

133

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

PubMed Central

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

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

2010-01-01

134

Effect of nickel–titanium shape memory metal alloy on bone formation  

Microsoft Academic Search

The aim of this study was to determine the biocompatibility of NiTi alloy on bone formation in vivo. For this purpose we used ectopic bone formation assay which goes through all the events of bone formation and calcification. Comparisons were made between Nitinol (NiTi), stainless steel (Stst) and titanium–aluminium (6%)–vanadium (4%) alloy (Ti–6Al–4V), which were implanted for 8 weeks under

Anita Kapanen; Jorma Ryhänen; Anatoli Danilov; Juha Tuukkanen

2001-01-01

135

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.

Rodriguez-Carballo, Edgardo; Gamez, Beatriz; Sedo-Cabezon, Lara; Sanchez-Feutrie, Manuela; Zorzano, Antonio; Manzanares-Cespedes, Cristina; Rosa, Jose Luis; Ventura, Francesc

2014-01-01

136

TSH Prevents Bone Resorption and with Calcitriol Synergistically Stimulates Bone Formation in Rats with Low Levels of Calciotropic Hormones.  

PubMed

Thyroid-stimulating hormone exerts both antiresorptive and anabolic effects on bone remodeling in aged ovariectomized rats and thyroid stimulating hormone-receptor null mice, supported by clinical results demonstrating that low thyroid-stimulating hormone level is associated with increased bone loss. To further explore the effect of thyroid-stimulating hormone on bone metabolism we introduced here a rat model with removed thyroid and parathyroid glands to obtain low serum concentrations of thyroid and parathyroid hormone, calcitonin and 1,25(OH)2D3. Surgery resulted in hypocalcemia, low parathyroid and thyroid hormone, 1,25(OH)2D3, C-telopeptide, and osteocalcin serum level. Intermittent administration of thyroid-stimulating hormone resulted in a further decrease of serum calcium and decreased level of serum C-telopeptide due to the suppression of bone resorption, while in the same animals osteocalcin in serum was higher indicating an increased bone formation rate. A combination of thyroid-stimulating hormone and 1,25(OH)2D3 significantly increased the serum Ca2+, C-telopeptide and serum osteocalcin values. MicroCT analyses of the distal femur and proximal tibia showed that rats treated with 1,25(OH)2D3 alone or in a combination with thyroid-stimulating hormone had an increased trabecular bone volume, and enhanced trabecular bone quality. Biomechanical testing of the trabecular bone showed an increased maximal load for 105% and 235%, respectively, in rats treated with 1,25(OH)2D3 alone, or in a combination with thyroid-stimulating hormone. We suggest that thyroid-stimulating hormone independently of calciotropic hormones suppressed bone resorption and stimulated bone formation, while in combination with 1,25(OH)2D3 acted synergistically on bone formation resulting in an increased bone volume. PMID:24446158

Dumic-Cule, I; Draca, N; Luetic, A T; Jezek, D; Rogic, D; Grgurevic, L; Vukicevic, S

2014-05-01

137

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.

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

2014-01-01

138

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

Microsoft Academic Search

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described

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

2003-01-01

139

In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer–bone morphogenetic protein matrices  

Microsoft Academic Search

Over 800,000 bone grafting procedures are performed in the United States annually, creating a demand for viable alternatives to autogenous bone, the grafting standard in osseous repair. The objective of this study was to examine the efficacy of a BMP-polymer matrix in inducing the expression of the osteoblastic phenotype and in vitro bone formation by muscle-derived cells. Specifically, we evaluated

Helen H. Lu; Michelle D. Kofron; Saadiq F. El-Amin; Mohammed A. Attawia; Cato T. Laurencinb

2003-01-01

140

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

NASA Astrophysics Data System (ADS)

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

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

2013-11-01

141

Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male  

Microsoft Academic Search

Summary Osteoporosis has been reported to complicate androgen deficiency in males. Accordingly, we have evaluated an osteoporotic hypogonadal male with bone histomorphometry before and after 6 months of testosterone replacement. Androgen therapy resulted in increases in relative osteoid volum, total osteoid surface, linear extent of bone formation, and bone mineralization. The dramatic histological response to hormonal replacement confirms the importance

Daniel T. Baran; Michele A. Bergfeld; Steven L. Teitelbaum; Louis V. Avioli

1978-01-01

142

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

PubMed

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

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

2008-11-28

143

Functionalized silk-based biomaterials for bone formation.  

PubMed

Silks are being reassessed as biomaterial scaffolds due to their unique mechanical properties, opportunities for genetic tailoring of structure and thus function, and recent studies clarifying biocompatibility. We report on the covalent decoration of silk films with integrin recognition sequences (RGD) as well as parathyroid hormone (PTH, 1-34 amino acids) and a modified PTH 1-34 (mPTH) involved in the induction of bone formation. Osteoblast-like cell (Saos-2) responses to the decorated silk films indicate that the proteins serve as suitable bone-inducing matrices. Osteoblast-like cell adhesion was significantly increased on RGD and PTH compared to plastic, mPTH, and the control peptide RAD. At 2 weeks of culture, message levels of alkaline phosphatase were similar on all substrates, but by 4 weeks, alkaline phosphatase mRNA was greatest on RGD. At 2 weeks of culture, alpha 1(I) procollagen mRNA was elevated on silk, RGD, RAD, and PTH, and hardly detectable on mPTH and plastic. However, by 4 weeks RGD demonstrated the highest level compared to the other substrates. Osteocalcin message levels detected by RT-PCR were greatest on RGD at both time points. Calcification was also significantly elevated on RGD compared to the other substrates with an increase in number and size of the mineralized nodules in culture. Thus, RGD covalently decorated silk appears to stimulate osteoblast-based mineralization in vitro. PMID:11077413

Sofia, S; McCarthy, M B; Gronowicz, G; Kaplan, D L

2001-01-01

144

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

Microsoft Academic Search

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

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

2007-01-01

145

INTERMITTENT PTH STIMULATES PERIOSTEAL BONE FORMATION BY ACTIONS ON POST-MITOTIC PREOSTEOBLASTS  

PubMed Central

Intermittent administration of parathyroid hormone (PTH) stimulates bone formation on the surface of cancellous and periosteal bone by increasing the number of osteoblasts. Previous studies of ours in mice demonstrated that intermittent PTH increases cancellous osteoblast number at least in part by attenuating osteoblast apoptosis, but the mechanism responsible for the anabolic effect of the hormone on periosteal bone is unknown. We report that daily injections of 100 ng/g of PTH(1–34) to 4–6 month old mice increased the number of osteoblasts on the periosteum of lumbar vertebrae by 2–3 fold as early as after 2 days. However, the prevalence of apoptotic periosteal osteoblasts was only 0.2% in vehicle treated animals, which is ~20-fold lower than is the case for cancellous osteoblasts. Moreover, PTH did not have a discernable effect on periosteal osteoblast apoptosis. Administration of BrdU for 4 days failed to label periosteal osteoblasts under either basal conditions or following administration of PTH. Cancellous osteoblasts, on the other hand, were labeled under basal conditions, but PTH did not increase the percentage of BrdU-positive cells. Thus, intermittent PTH does not increase cancellous or periosteal osteoblast number by stimulating the proliferation of osteoblast progenitors. Consistent with high turnover of cancellous osteoblasts as compared to that of periosteal osteoblasts, ganciclovir-induced ablation of replicating osteoblast progenitors in mice expressing thymidine kinase under the control of the 3.6kb rat Col1A1 promoter resulted in disappearance of osteoblasts from cancellous bone over a 7–14 day period, whereas periosteal osteoblasts were unaffected. However, 14 days of pre-treatment with ganciclovir prevented PTH anabolism on periosteal bone. We conclude that in cancellous bone, attenuation of osteoblast apoptosis by PTH increases osteoblast number because their rate of apoptosis is high, making this effect of the hormone profound. However, in periosteal bone where the rate of osteoblast apoptosis is low, PTH must exert pro-differentiating and/or pro-survival effects on post-mitotic pre-osteoblasts. Targeting the latter cells is an effective mechanism for increasing osteoblast number in periosteal bone where the production of osteoblasts from replicating progenitors is slow.

Jilka, Robert L.; O'Brien, Charles A.; Ali, A. Afshan; Roberson, Paula; Weinstein, Robert S.; Manolagas, Stavros C.

2009-01-01

146

Type XII collagen regulates osteoblast polarity and communication during bone formation  

PubMed Central

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

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

2011-01-01

147

Expression of PGK1 By Prostate Cancer Cells Induces Bone Formation  

PubMed Central

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

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

2009-01-01

148

Alginate hydrogels containing cell-interactive beads for bone formation.  

PubMed

Alginate hydrogels containing cell-instructive cues are the subject of intense interest for their use as cell carriers in bone tissue engineering. Peptides and proteins are chemically grafted onto these hydrophilic materials to facilitate adhesion and direct phenotype of entrapped cells. However, the presentation of a single or small number of peptides does not represent the complexity of the native extracellular matrix (ECM) of bony tissues. Mesenchymal stem cells (MSCs) secrete ECM that can be harvested and deposited on various substrata to promote osteogenic differentiation. In this study, we hypothesized that the presentation of engineered cell-secreted ECM on microbeads suspended in alginate hydrogels would promote cell adhesion and enhance osteogenic differentiation of undifferentiated MSCs without chemical incorporation of cell-adhesive peptides. Human MSCs entrapped in alginate hydrogels loaded with ECM-coated beads showed increased interaction with beads, when compared with cells suspended in hydrogels containing uncoated blank (BLK) beads. MSCs entrapped in ECM gels exhibited increased alkaline phosphatase (ALP) activity and expression of osteogenic genes in vitro compared with hydrogels modified with arginine-glycine-aspartic acid (RGD)-containing peptides. Transplantation of MSCs into an ectopic site resulted in significant increases in blood vessel density for ECM hydrogels when compared with the BLK or RGD gels. Furthermore, we observed comparable levels of bone formation at 6 wk with ECM and RGD hydrogels. These findings demonstrate that engineered ECM can be deployed in a minimally invasive manner to direct the formation of bony tissue. This strategy may provide an alternative to the engraftment of proteins or peptides onto the polymer backbone of hydrogels for directing cellular behavior. PMID:24005905

Bhat, Archana; Hoch, Allison I; Decaris, Martin L; Leach, J Kent

2013-12-01

149

Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs.  

PubMed

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible. PMID:11936403

Nagao, H; Tachikawa, N; Miki, T; Oda, M; Mori, M; Takahashi, K; Enomoto, S

2002-02-01

150

Massive star formation in early-type spirals  

Microsoft Academic Search

I present results from an Halpha imaging survey of 51 nearby early-type (Sa-Sab) spiral galaxies. Halpha emission line flux is one of the best tracers of high mass star formation. Prior to this imaging campaign early-type spirals were considered as a homogeneous group of galaxies with predominantly low rates massive star formation rates. One of the most surprising results from

Salman Arshad Hameed

2001-01-01

151

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

PubMed Central

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

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

2013-01-01

152

Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis.  

PubMed Central

Osteoporosis is a state of reduced skeletal mass characterized by various rates of bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in bone remodeling. The possible role(s) of these factors in the pathogenesis of osteoporosis is unknown. One such factor, interleukin 1 (IL-1), is of particular interest, as this protein is known to stimulate bone resorption and perhaps formation. Consequently, we have measured the spontaneous secretion of IL-1 activity by cultured peripheral blood monocytes obtained from 22 osteoporotic patients and 14 age-matched control subjects. Monocytes from osteoporotic patients produced more IL-1 than did monocytes from control subjects. When patients were grouped according to monocyte-produced IL-1 activity, dynamic parameters of bone formation, as judged by quantitative histomorphometric analysis of iliac crest bone biopsies and by circulating levels of bone 4-carboxyglutamic acid protein (BGP)--a marker of bone formation--were higher in subjects with elevated IL-1 activity; whereas, indices of bone resorption and static indices of bone formation were similar in subjects with either high or normal IL-1 activity. IL-1 activity released by peripheral blood monocytes appears to reflect bone formation rate in osteoporotic patients and may be of pathogenetic significance in a subset of individuals with osteoporosis.

Pacifici, R; Rifas, L; Teitelbaum, S; Slatopolsky, E; McCracken, R; Bergfeld, M; Lee, W; Avioli, L V; Peck, W A

1987-01-01

153

A comparison of Indomethacin and Diclofenac in the inhibition of experimental heterotopic new bone formation  

Microsoft Academic Search

The effect of the two nonsteroidal antiinflammatory drugs Diclofenac and Indomethacin on the formation of heterotropic and orthotopic bone in rats was compared. Experimental heterotopic bone formation was induced by implanting demineralized bone matrix into the abdominal wall of rats. Indomethacin (3 mg\\/kg), Diclofenac (3, 6 or 12 mg\\/kg), or saline were given as daily subcutaneous injections. 3H-proline and 45Ca

O. S. Nilsson; H. C. F. Bauer; O. Brosjö; H. Törnkvist

1987-01-01

154

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

PubMed

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

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

2013-05-01

155

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

PubMed Central

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

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

2013-01-01

156

Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF 164 and VEGF 188  

Microsoft Academic Search

Vascular endothelial growth factor (VEGF)-mediated angiogenesis is an important part of bone formation. To clarify the role of VEGF isoforms in endochondral bone formation, we examined long bone development in mice expressing exclusively the VEGF120 isoform (VEGF120\\/120 mice). Neonatal VEGF120\\/120 long bones showed a completely disturbed vascular pattern, concomitant with a 35% decrease in trabecular bone volume, reduced bone growth

Christa Maes; Peter Carmeliet; Karen Moermans; Ingrid Stockmans; Nico Smets; Désiré Collen; Roger Bouillon; Geert Carmeliet

2002-01-01

157

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

158

Aromatase inhibitors-induced bone loss in early breast cancer  

PubMed Central

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.

Body, Jean-Jacques

2012-01-01

159

In vivo micro-computed tomography allows direct three-dimensional quantification of both bone formation and bone resorption parameters using time-lapsed imaging  

Microsoft Academic Search

Bone is a living tissue able to adapt its structure to external influences such as altered mechanical loading. This adaptation process is governed by two distinct cell types: bone-forming cells called osteoblasts and bone-resorbing cells called osteoclasts. It is therefore of particular interest to have quantitative access to the outcomes of bone formation and resorption separately. This article presents a

Friederike A. Schulte; Floor M. Lambers; Gisela Kuhn; Ralph Müller

2011-01-01

160

Early models of DNA damage formation  

NASA Astrophysics Data System (ADS)

Quantification of DNA damage, induced by various types of incident radiation as well as chemical agents, has been the subject of many theoretical and experimental studies, supporting the development of modern cancer therapy. The primary observations showed that many factors can lead to damage of DNA molecules. It became clear that the development of experimental techniques for exploring this phenomenon is required. Another problem was simultaneously dealt with, anticipating on how the damage is distributed within the double helix of the DNA molecule and how the single strand break formation and accumulation can influence the lethal double strand break formation. In this work the most important probabilistic models for DNA strand breakage and damage propagation are summarized and compared.

?mia?ek, Ma?gorzata A.

2012-07-01

161

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

162

Early vascular changes in rabbit subchondral bone after repetitive impulsive loading.  

PubMed

The sequence of vascular and bony changes that precedes experimental osteoarthrosis was observed in rabbits. The subchondral bone underlying the weight-bearing portion of the medial tibial condyle and the talocalcaneal joint were examined after two, three, and six weeks of 50-ms and 500-ms repetitive loading at 1 Hz for 40 minutes each day. Vascular alterations were evident in the subchondral bone of the talocalcaneal joint after three weeks of a 50-ms load regime. A 10% increase in bone mass and a significant increase in the number of small diameter vessels were observed after six weeks. No changes were observed in the tibial subchondral bone, consistent with the measured attenuation of load distal to this joint. No changes were observed in either tibial or calcaneal subchondral bone in the 500-ms load group. Impulsive loading promotes early vascular changes in subchondral bone, which are developed in response to both the magnitude and the rate of loading. PMID:3581578

Farkas, T; Boyd, R D; Schaffler, M B; Radin, E L; Burr, D B

1987-06-01

163

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

PubMed

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

Crane, Janet L; Cao, Xu

2014-02-01

164

Insulin-like Growth Factor 2 (IGF-2) Potentiates BMP-9-Induced Osteogenic Differentiation and Bone Formation  

PubMed Central

Efficient osteogenic differentiation and bone formation from mesenchymal stem cells (MSCs) should have clinical applications in treating nonunion fracture healing. MSCs are adherent bone marrow stromal cells that can self-renew and differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. We have identified bone morphogenetic protein 9 (BMP-9) as one of the most osteogenic BMPs. Here we investigate the effect of insulin-like growth factor 2 (IGF-2) on BMP-9-induced bone formation. We have found that endogenous IGF-2 expression is low in MSCs. Expression of IGF-2 can potentiate BMP-9-induced early osteogenic marker alkaline phosphatase (ALP) activity and the expression of later markers. IGF-2 has been shown to augment BMP-9-induced ectopic bone formation in the stem cell implantation assay. In perinatal limb explant culture assay, IGF-2 enhances BMP-9-induced endochondral ossification, whereas IGF-2 itself can promote the expansion of the hypertropic chondrocyte zone of the cultured limb explants. Expression of the IGF antagonists IGFBP3 and IGFBP4 leads to inhibition of the IGF-2 effect on BMP-9-induced ALP activity and matrix mineralization. Mechanistically, IGF-2 is further shown to enhance the BMP-9-induced BMPR-Smad reporter activity and Smad1/5/8 nuclear translocation. PI3-kinase (PI3K) inhibitor LY294002 abolishes the IGF-2 potentiation effect on BMP-9-mediated osteogenic signaling and can directly inhibit BMP-9 activity. These results demonstrate that BMP-9 crosstalks with IGF-2 through PI3K/AKT signaling pathway during osteogenic differentiation of MSCs. Taken together, our findings suggest that a combination of BMP-9 and IGF-2 may be explored as an effective bone-regeneration agent to treat large segmental bony defects, nonunion fracture, and/or osteoporotic fracture. © 2010 American Society for Bone and Mineral Research.

Chen, Liang; Jiang, Wei; Huang, Jiayi; He, Bai-Cheng; Zuo, Guo-Wei; Zhang, Wenli; Luo, Qing; Shi, Qiong; Zhang, Bing-Qiang; Wagner, Eric R; Luo, Jinyong; Tang, Min; Wietholt, Christian; Luo, Xiaoji; Bi, Yang; Su, Yuxi; Liu, Bo; Kim, Stephanie H; He, Connie J; Hu, Yawen; Shen, Jikun; Rastegar, Farbod; Huang, Enyi; Gao, Yanhong; Gao, Jian-Li; Zhou, Jian-Zhong; Reid, Russell R; Luu, Hue H; Haydon, Rex C; He, Tong-Chuan; Deng, Zhong-Liang

2010-01-01

165

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.

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

2012-01-01

166

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

167

Early-type galaxy formation history from GALEX-SAURON  

NASA Astrophysics Data System (ADS)

One of long-standing debates in modern astrophysics is the formation mechanism of early-type galaxies. The classical model, proposed by Eggel et al. (1962), explains that early-type stellar populations form in an initial highly efficient burst and evolve without further star formation until present day. The high Mg and alpha abundances found in bright elliptical galaxies support such scenarios. Early-type galaxies, therefore, are traditionally believed that they are dynamically simple stellar systems with homogeneous stellar populations (e.g. Gott 1977). The popular Lambda Cold Dark Matter (LCDM) paradigm (e.g. Toomre and Toomre 1972), however, strongly suggested a hierarchical merger picture for massive elliptical galaxies. In this model, early-type galaxies form as a result of major mergers and are thought to have continued star formation. Evidence is growing that a substantial fraction of early-type galaxies has secondary star formation. Furthermore, SAURON survey has revealed a rich diversity in the kinematics, discovering numerous central disks and kinematically decoupled cores (e.g. Emsellem et al. 2004; Sarzi et al. 2006). Early-type galaxies are thus likely to have had complex and varied formation histories.

Jeong, Hyunjin; Yi, Sukyoung K.; Bureau, Martin; Kranovi?, Davor; Davies, Roger L.

2008-07-01

168

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

SciTech Connect

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

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

1991-08-01

169

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

PubMed Central

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

Wong, Ricky WK; Rabie, Bakr

2008-01-01

170

Enhanced Bone Morphogenetic Protein-2-Induced Ectopic and Orthotopic Bone Formation by Intermittent Parathyroid Hormone (1-34) Administration  

PubMed Central

Bone morphogenetic proteins (BMPs) play a central role in local bone regeneration strategies, whereas the anabolic features of parathyroid hormone (PTH) are particularly appealing for the systemic treatment of generalized bone loss. The aim of the current study was to investigate whether local BMP-2-induced bone regeneration could be enhanced by systemic administration of PTH (1–34). Empty or BMP-2-loaded poly(lactic-co glycolic acid)/poly(propylene fumarate)/gelatin composites were implanted subcutaneously and in femoral defects in rats (n?=?9). For the orthotopic site, empty defects were also tested. Each of the conditions was investigated in combination with daily administered subcutaneous PTH (1–34) injections in the neck. After 8 weeks of implantation, bone mineral density (BMD) and bone volume were analyzed using microcomputed tomography and histology. Ectopic bone formation and almost complete healing of the femoral defect were only seen in rats that received BMP-2-loaded composites. Additional treatment of the rats with PTH (1–34) resulted in significantly (p?bone volume in the BMP-2 composites at both implantation sites. Despite its effect on BMD in the humerus and vertebra, PTH (1–34) treatment had no significant effect on BMD and bone volume in the empty femoral defects and the ectopically or orthotopically implanted empty composites. Histological analysis showed that the newly formed bone had a normal woven and trabecular appearance. Overall, this study suggests that intermittent administration of a low PTH dose alone has limited potential to enhance local bone regeneration in a critical-sized defect in rats. However, when combined with local BMP-2-releasing scaffolds, PTH administration significantly enhanced osteogenesis in both ectopic and orthotopic sites.

Kempen, Diederik H.R.; Hefferan, Theresa E.; Creemers, Laura B.; Heijink, Andras; Maran, Avudaiappan; Dhert, Wouter J.A.; Yaszemski, Michael J.

2010-01-01

171

Discordance between MRI and bone scan findings in a child with acute complicated osteomyelitis: scintigraphic features that contribute to the early diagnosis.  

PubMed

Early diagnosis and prompt treatment of acute osteomyelitis are of paramount importance in children because they can prevent irreversible bone damage. Magnetic resonance imaging (MRI) with its superior spatial resolution and lack of ionizing radiation is routinely preferred over bone scan for this purpose. Increased blood flow, hyperemia and focally increased tracer uptake shown by "three phase" bone scan are the typical scintigraphic findings of acute osteomyelitis. In addition, diffuse uptake along the shaft of long bones and focal "cold" lesions are two special features that may be highly suggestive of infective periostitis, soft tissue sepsis and subperiosteal abscess formation, due to the loose attachment of periosteum to bone during childhood. We present a case of complicated osteomyelitis in a child with inconclusive MRI correctly diagnosed on the basis of these special scintigraphic findings resulting in treatment change from double i.v. Vancomycin--Ceftriaxone scheme to surgical intervention. PMID:23938190

Mpalaris, V; Arsos, G; Iakovou, I; Dalpa, E; Karatzas, N

2014-01-01

172

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

Microsoft Academic Search

BackgroundAppropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.Methodology and Principal FindingsIn this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or

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

2011-01-01

173

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

PubMed Central

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

McKenzie, Jennifer A.; Silva, Matthew J.

2010-01-01

174

Relation of early menarche to high bone mineral density  

Microsoft Academic Search

The study of background factors in individuals with high bone mineral density (BMD) may provide useful information in the prevention of osteoporosis. We investigated the relationship of reproductive factors to BMD. In 519 female volunteers (327 postmenopausal and 192 premenopausal women) ranging in age from 21 to 74 (mean 52.3 ±11.8) years, spinal BMD values were obtained using both quantitative

M. Ito; M. Yamada; K. Hayashi; M. Ohki; M. Uetani; T. Nakamura

1995-01-01

175

Reduced Limbic and Hypothalamic Volumes Correlate with Bone Density in Early Alzheimer's Disease  

PubMed Central

Accelerated bone loss is associated with Alzheimer’s disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

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

2010-01-01

176

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

PubMed Central

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

2013-01-01

177

Strontium-calcium coadministration stimulates bone matrix osteogenic factor expression and new bone formation in a large animal model.  

PubMed

Strontium (Sr) has become increasingly attractive for use in the prevention and treatment of osteoporosis by concomitantly inhibiting bone resorption and enhancing bone formation. Strontium shares similar chemical, physical, and biological characteristics with calcium (Ca), which has been widely used as a dietary supplement in osteoporosis. However, the effects of Sr-Ca coadministration on bone growth and remodeling are yet to be extensively reported. In this study, 18 ovariectomized goats were divided into four groups: three groups of five goats each treated with 100 mg/kg/day Ca, Ca plus 24 mg/kg/day Sr (Ca + 24Sr), or Ca plus 40 mg/kg/day Sr (Ca + 40Sr), and three untreated goats fed low calcium feed. Serum Sr levels increased 6- and 10-fold in the Ca + 24Sr and Ca + 40Sr groups, respectively. Similarly, Sr in the bone increased four- and sixfold in these two groups. Sr-Ca coadministration considerably increased bone mineral apposition rate (MAR). The expression of insulin-like growth factor (IGF)-1 and runt-related transcription factor 2 (Runx2) was significantly upregulated within the Ca + 40Sr treatment group; tumor necrosis factor (TNF)-agr; expression was significantly downregulated in the Ca and Ca + 40Sr groups. The results indicate that Sr-Ca coadministration increases osteogenic gene expression and stimulates new bone formation. PMID:19025756

Li, Zhaoyang; Lu, William W; Chiu, Peter K Y; Lam, Raymond W M; Xu, Bing; Cheung, Kenneth M C; Leong, John C Y; Luk, Keith D K

2009-06-01

178

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.

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

2013-01-01

179

The effect of three hemostatic agents on early bone healing in an animal model  

Microsoft Academic Search

BACKGROUND: Resorbable bone hemostasis materials, oxidized regenerated cellulose (ORC) and microfibrillar collagen (MFC), remain at the site of application for up to 8 weeks and may impair osteogenesis. Our experimental study compared the effect of a water-soluble alkylene oxide copolymer (AOC) to ORC and MFC versus no hemostatic material on early bone healing. METHODS: Two circular 2.7 mm non-critical defects

Jonathan K Armstrong; Bo Han; Kenrick Kuwahara; Zhi Yang; Clara E Magyar; Sarah M Dry; Elisa Atti; Sotirios Tetradis; Timothy C Fisher

2010-01-01

180

No evidence to indicate topographic dependency on bone formation around cp titanium implants under masticatory loading.  

PubMed

In vitro studies have proved the topographic dependency upon osteogenesis on titanium plate by investigating the cell-adhesion, -shape, -proliferation, -differentiation, ALP activity and osteocalcin production of osteogenic stem cells, MG36, MC3T3-E1 and wild strains of bone formative cells from animal and human. However, this in vivo study on bone growth around cp titanium dental implants under masticatory loading did not demonstrate significant difference among the different surface roughness in the range of Ra 0.4-1.9 microm, Rz 2.8-11.2 microm, Rmax 3.6-28.1 microm and Sm 2.9-41.0 microm, which was estimated by measuring the bone contacts, bone occupancies and bone bonding strengths at the implant/bone marrow interface. It is revealed that the topographic dependency on the osteogenetic activity is apt to be covered with wide variation in bone healing potential under the clinical condition with functional biting load. PMID:16897165

Kawahara, H; Aoki, H; Koike, H; Soeda, Y; Kawahara, D; Matsuda, S

2006-08-01

181

Cannabinoids Stimulate Fibroblastic Colony Formation by Bone Marrow Cells Indirectly via CB 2 Receptors  

Microsoft Academic Search

Recently, the cannabinoid receptors CB1 and CB2 were shown to modulate bone formation and resorption in vivo, although little is known of the mechanisms underlying this. The effects of cannabinoids on mesenchymal stem cell (MSC) recruitment\\u000a in whole bone marrow were investigated using either the fibroblastic colony-forming unit (CFU-f) assay or high-density cultures\\u000a of whole bone marrow. Levels of the

A. Scutt; E. M. Williamson

2007-01-01

182

Formation of biologically active bone-like apatite on metals and polymers by a biomimetic process  

Microsoft Academic Search

Some ceramics bond to living bone through a bone-like apatite layer which is formed on their surfaces in the living body. The formation of the apatite layer is induced by Si?OH or Ti?OH groups on their surfaces. These findings provide us with a biomimetic process with which to form a bone-like apatite layer on metals and organic polymers. Titanium metal

T. Kokubo

1996-01-01

183

Suppressive effects of Anoectochilus formosanus extract on osteoclast formation in vitro and bone resorption in vivo.  

PubMed

Anoectochilus formosanus, a plant native to Taiwan, is used as a folk medicine. It was found that oral administration of A. formosanus extract (AFE) (500 mg/kg) for 4 weeks suppressed bone weight loss and trabecular bone loss in ovariectomized mice, an experimental model of osteoporosis. Although AFE at 12.5 and 25 mug/ml inhibited osteoclast formation in co-culture of osteoblasts and bone marrow cells, AFE did not inhibit the formation of osteoclast progenitor cells and preosteoclast cells in bone marrow cells and RAW264 cells. However, AFE (at 12.5 and 25 microg/ml) decreased RANKL expression. These results suggested that AFE might suppress the bone loss caused by estrogen deficiency through suppression of RANKL expression required for osteoclast formation. PMID:18301967

Masuda, Kikuko; Ikeuchi, Mayumi; Koyama, Tomoyuki; Yamaguchi, Kohji; Woo, Je-Tae; Nishimura, Tomio; Yazawa, Kazunaga

2008-01-01

184

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

PubMed Central

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

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

2012-01-01

185

Epicardial GATA factors regulate early coronary vascular plexus formation.  

PubMed

During early development, GATA factors have been shown to be important for key events of coronary vasculogenesis, including formation of the epicardium. Myocardial GATA factors are required for coronary vascular (CV) formation; however, the role of epicardial localized GATAs in this process has not been addressed. The current study was conducted to investigate the molecular mechanisms by which the epicardium controls coronary vasculogenesis, focusing on the role of epicardial GATAs in establishing the endothelial plexus during early coronary vasculogenesis. To address the role of epicardial GATAs, we ablated GATA4 and GATA6 transcription factors specifically from the mouse epicardium and found that the number of endothelial cells in the sub-epicardium was drastically reduced, and concomitant coronary vascular plexus formation was significantly compromised. Here we present evidence for a novel role for epicardial GATA factors in controlling plexus formation by recruiting endothelial cells to the sub-epicardium. PMID:24380800

Kolander, Kurt D; Holtz, Mary L; Cossette, Stephanie M; Duncan, Stephen A; Misra, Ravi P

2014-02-01

186

The effect of semelil (angipars(R)) 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.

2012-01-01

187

Continuous Treatment with a Low-Dose ?-Agonist Reduces Bone Mass by Increasing Bone Resorption Without Suppressing Bone Formation  

Microsoft Academic Search

The sympathetic nervous system regulates bone remodeling through the ?-adrenergic receptor (?-AR). However, the systemic roles\\u000a of adrenergic actions on bone remodeling through the ?-AR are largely unknown. In this study, we examined the dose effect\\u000a of continuous treatment with isoprenaline, a nonspecific ?-AR agonist, on bone remodeling. Male C57BL\\/6J mice were intrasubcutaneously\\u000a administrated with four different doses (5, 25,

Hisataka Kondo; Akifumi Togari

2011-01-01

188

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

PubMed

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

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

2013-02-01

189

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

Microsoft Academic Search

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

Jane E. Aubin; Shulin Zhang; Soshi Uchida

190

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

Microsoft Academic Search

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

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

1992-01-01

191

Alteration of newly induced endochondral bone formation in adult mice without tumour necrosis factor receptor 1  

PubMed Central

Tumour necrosis factor (TNF)-?, a major proinflammatory cytokine, exerts its role on bone cells through two receptors (TNFR1 and TNFR2). TNFR1, but not TNFR2, is expressed by osteoblasts and its function in bone formation in vivo is not fully understood. We compared in vivo new bone formation in TNFR1-deficient (TNFR1–/–) mice and wild-type mice, using two models of bone formation: intramembranous ossification following tibial marrow ablation and endochondral ossification induced by bone morphogenetic protein (BMP)-2. Intramembranous osteogenesis in TNFR1–/– mice did not differ from the wild-type mice either in histomorphometric parameters or mRNA expression of bone-related markers and inflammatory cytokines. During endochondral osteogenesis, TNFR1–/– mice formed more cartilage (at post-implantation day 9), followed by more bone and bone marrow (at day 12). mRNAs for BMP-2, -4 and -7 were increased during the endochondral differentiation sequence in TNFR1–/– mice. The expression of receptor activator of NF-?B ligand (RANKL) and receptor activator of NF-?B (RANK), as assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR), was also increased significantly during endochondral ossification in TNFR1–/– mice. In conclusion, signalling through the TNFR1 seems to be a negative regulator of new tissue formation during endochondral but not intramembranous osteogenesis in an adult organism. BMPs and RANKL and its receptor RANK may be involved in the change of local environment in the absence of TNFR1 signalling.

Lukic, I K; Grcevic, D; Kovacic, N; Katavic, V; Ivcevic, S; Kalajzic, I; Marusic, A

2005-01-01

192

Drosophila Transforming Growth Factor beta Superfamily Proteins Induce Endochondral Bone Formation in Mammals  

Microsoft Academic Search

Both decapentaplegic (dpp) protein and 60A protein have been implicated in pattern formation during Drosophila melanogaster embryogenesis. Within the C-terminal domain, dpp and 60A are similar to human bone morphogenetic protein 2 (75% identity) and human osteogenic protein 1 (70% identity), respectively. Both recombinant human bone morphogenetic protein 2 and recombinant human osteogenic protein 1 have been shown to induce

T. K. Sampath; K. E. Rashka; J. S; R. F. Tucker; F. M. Hoffmann

1993-01-01

193

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

Microsoft Academic Search

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

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

1999-01-01

194

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

PubMed

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

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

2008-02-01

195

A tissue-like construct of human bone marrow MSCs composite scaffold support in vivo ectopic bone formation.  

PubMed

Biocompatible and osteoconductive cell-scaffold constructs comprise the first and most important step towards successful in vivo bone repair. This study reports on a new cell-scaffold construct composed of gelatin-based hydrogel and ceramic (CaCO(3)/beta-TCP) particles loaded with human MSCs producing a tissue-like construct applied as a transplant for in vivo bone formation. Bone marrow-derived human MSCs were cultured in osteogenic induction medium. 5 x 10(5) (P(2)) cells were loaded on a mixture of hydrogel microspheres and ceramic particles, cultured in a rotating dynamic culture for up to 3 weeks. Both hydrogel microspheres and ceramic particles coalesced together to form a tissue-like construct, shown by histology to contain elongated spindle-like cells forming the new tissue between the individual particles. Cell proliferation and cell viability were confirmed by Alamar blue assay and by staining with CFDA, respectively. FACS analysis conducted before loading the cells, and after formation of the construct, revealed that the profile of cell surface markers remained unchanged throughout the dynamic culture. The osteogenic potential of the cells composing the tissue-like construct was further validated by subcutaneous transplants in athymic nude mice. After 8 weeks a substantial amount of new bone formation was observed in the cell-construct transplants, whereas no bone formation was observed in transplants containing no cells. This new cell construct provides a system for in vivo bone transplants. It can be tailored for a specific size and shape as needed for various transplant sites and for all aspects of regenerative medicine and biomaterial science. PMID:19842114

Ben-David, D; Kizhner, T; Livne, E; Srouji, S

2010-01-01

196

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

PubMed Central

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

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

2009-01-01

197

The effect of short term treatment with alendronate on vertebral density and biochemical markers of bone remodeling in early postmenopausal women.  

PubMed

The effects of oral alendronate treatment on spinal bone mineral density and biochemical markers of bone turnover were assessed in women in the early postmenopausal period. Sixty-five women were treated with placebo or 5, 20, or 40 mg alendronate daily for 6 weeks in a double blind study. Treatment with alendronate decreased both urinary markers of bone resorption (pyridinolines, hydroxyproline, and calcium) and serum markers of bone formation (osteocalcin and alkaline phosphatase) in a dose-dependent fashion. This short term treatment with alendronate also produced a dose-dependent increase in lumbar bone mineral density measured 7.5 months after the completion of therapy. Median percent changes in integral spinal bone mineral density, as assessed by dual x-ray absorptiometry, were -2.3, -1.2, +0.7, and +1.2 after treatment with placebo and 5, 20, and 40 mg alendronate, respectively. Treatment with alendronate was well tolerated and produced no fever; gastrointestinal intolerance was no more common than with placebo treatment. Short term alendronate treatment in early postmenopausal women decreased bone turnover and increased vertebral density. PMID:8501142

Harris, S T; Gertz, B J; Genant, H K; Eyre, D R; Survill, T T; Ventura, J N; DeBrock, J; Ricerca, E; Chesnut, C H

1993-06-01

198

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

PubMed

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

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

2012-07-01

199

Massive star formation in early-type spirals  

NASA Astrophysics Data System (ADS)

I present results from an H? imaging survey of 51 nearby early-type (Sa-Sab) spiral galaxies. H? emission line flux is one of the best tracers of high mass star formation. Prior to this imaging campaign early-type spirals were considered as a homogeneous group of galaxies with predominantly low rates massive star formation rates. One of the most surprising results from my dissertation has been the discovery of a significant fraction of early-type spirals that host giant HII regions and exhibit massive star formation rates comparable to the high star forming Sc galaxies. A determination of the H? morphology and a measure of the H? luminosity suggest that early- type spirals can be divided into two categories based on the H? luminosity of the largest HII region in the disk. The first category includes galaxies for which the individual HII regions have H? luminosity LH? < 1039erg s-1. On the other hand, there is at least one HII in the disk of category 2 galaxies with LH? > 1039erg s-1. Category 1 galaxies exhibit diverse nuclear properties but appear undisturbed in the continuum image. Dust lanes and/or tidal tails are more frequent in Category 2 galaxies and have high H? and far-infrared luminosities. Approximately 37% of nearby early-type spirals belong to Category 2. Our observations reveal early-type spirals to be a heterogeneous class of galaxies that are evolving in the current epoch. HII region luminosity functions for a sub- sample of galaxies have also been obtained to understand the properties of individual star forming regions in early-type spirals. The results reveal a wide diversity in luminosity function shapes. In general, HII regions in Category 2 galaxies are more luminous than Category 1 early-type spirals. Thus, the difference in global H? luminosities between the two categories of early-type spirals is not attributable to just one anomalous HII region, but rather suggests intrinsic differences in the ensemble of HII regions found in the two categories of galaxies. The surprising presence of giant HII regions and high massive star formation rates in Sa-Sab galaxies may be related to interactions. HI maps of 9 high star forming early-type spirals have been analyzed and our HI maps reveal startling results. Eight out of nine high star forming Sa-Sab galaxies show either tidal tails or bridges in HI, suggesting that, perhaps, interactions play an important role in the evolution of early-type spirals.

Hameed, Salman Arshad

2001-12-01

200

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

PubMed

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

2014-06-10

201

Prediction of spatio-temporal bone formation in scaffold by diffusion equation.  

PubMed

Developing a successful bone tissue engineering strategy entails translation of experimental findings to clinical needs. A major leap forward toward this goal is developing a quantitative tool to predict spatial and temporal bone formation in scaffold. We hypothesized that bone formation in scaffold follows diffusion phenomenon. Subsequently, we developed an analytical formulation for bone formation, which had only three unknown parameters: C, the final bone volume fraction, ?, the so-called scaffold osteoconduction coefficient, and h, the so-called peri-scaffold osteoinduction coefficient. The three parameters were estimated by identifying the model within vivo data of polymeric scaffolds implanted in the femoral condyle of rats. In vivo data were obtained by longitudinal micro-CT scanning of the animals. Having identified the three parameters, we used the model to predict the course of bone formation in two previously published in vivo studies. We found the predicted values to be consistent with the experimental ones. Bone formation into a scaffold can then adequately be described through diffusion phenomenon. This model allowed us to spatially and temporally predict the outcome of tissue engineering scaffolds with only 3 physically relevant parameters. PMID:21700329

Roshan-Ghias, Alireza; Vogel, Arne; Rakotomanana, Lalaonirina; Pioletti, Dominique P

2011-10-01

202

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

MedlinePLUS

... ankylosing spondylitis (AS) is sometimes known as "fusing". Fusion of the spine and other joints, such as ... The authors of the study conclude that "Our data supports the hypothesis that new bone formation is ...

203

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

PubMed

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

2012-10-01

204

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

PubMed Central

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

Lipton, Allan

2011-01-01

205

Transdermal Nitroglycerin Therapy May Not Prevent Early Postmenopausal Bone Loss  

PubMed Central

Context: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. Objective: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. Design: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. Setting: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). Participants: Participants included 186 postmenopausal women aged 40–65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to ?2.5. Intervention: Women, stratified by lumbar T-score (5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. Measurements: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. Results: After 36 months of therapy, changes of ?2.1% in the active group (n = 88) and ?2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval ?1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different. Conclusions: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only ?16 mg/d); a sub-therapeutic dose.

Wimalawansa, Sunil J.; Grimes, Julia P.; Wilson, Alan C.; Hoover, Donald R.

2009-01-01

206

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

PubMed Central

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

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

2013-01-01

207

Timing of Childhood Events and Early-Adult Household Formation.  

ERIC Educational Resources Information Center

Identified a number of risk factors contributing to early household formation. Found that for girls, factors included mother's educational level and birth order; for boys, parental divorce at any stage of childhood. Risk factors common to boys and girls were age of mother at time of child's birth and race. (HTH)

Hill, Martha S.; And Others

1996-01-01

208

Enhanced prostacyclin formation and Wnt signaling in sclerostin deficient osteocytes and bone.  

PubMed

We show that prostacyclin production is increased in bone and osteocytes from sclerostin (Sost) knockout mice which have greatly increased bone mass. The addition of prostacyclin or a prostacyclin analog to bone forming osteoblasts enhances differentiation and matrix mineralization of osteoblasts. The increase in prostacyclin synthesis is linked to increases in ?-catenin concentrations and activity as shown by enhanced binding of lymphoid enhancer factor, Lef1, to promoter elements within the prostacyclin synthase promoter. Blockade of Wnt signaling reduces prostacyclin production in osteocytes. Increased prostacyclin production by osteocytes from sclerostin deficient mice could potentially contribute to the increased bone formation seen in this condition. PMID:24780398

Ryan, Zachary C; Craig, Theodore A; Salisbury, Jeffrey L; Carpio, Lomeli R; McGee-Lawrence, Meghan; Westendorf, Jennifer J; Kumar, Rajiv

2014-05-23

209

Bone formation and resorption biological markers in cosmonauts during and after a 180-day space flight (Euromir 95)  

Microsoft Academic Search

Long-term spaceflights induce bone loss as a result of profound modifications of bone remodeling, the modal- ities of which remain unknown in humans. We mea- sured intact parathyroid hormone (PTH) and serum calcium; for bone formation, serum concentrations of bone alkaline phosphatase (BAP), intact osteocalcin (iBGP), and type 1 procollagen propeptide (PICP); for resorption, urinary concentrations (normalized by creat- inine)

Anne Caillot-Augusseau; Marie-Helene Lafage-Proust; Claude Soler; Josiane Pernod; Francis Dubois; Christian Alexandre

210

Fibroblast growth factor-2 and vascular endothelial growth factor mediated augmentation of angiogenesis and bone formation in vascularized bone allotransplants.  

PubMed

We previously demonstrated recipient-derived neoangiogenesis to maintain viability of living bone allogeneic transplants without long-term immunosuppression. The effect of cytokine delivery to enhance this process is studied. Vascularized femur transplantation was performed from Dark Agouti to Piebald Virol Glaxo rats. Poly(d,l-lactide-co-glycolide) microspheres loaded with buffer (N?=?11), basic fibroblast growth factor (FGF2) (N?=?10), vascular endothelial growth factor (VEGF) (N?=?11), or both (N?=?11) were inserted intramedullarly alongside a recipient-derived arteriovenous bundle. FK-506 was administered for 2 weeks. At 18 weeks, bone blood flow, microangiography, histologic, histomorphometric, and alkaline phosphatase measurements were performed. Bone blood flow was greater in the combined group than control and VEGF groups (P?=?0.04). Capillary density was greater in the FGF2 group than in the VEGF and combined groups (P?Bone viability, growth, and alkaline phosphatase activity did not vary significantly between groups. Neoangiogenesis in vascularized bone allotransplants is enhanced by angiogenic cytokine delivery, with results using FGF2 that are comparable to isotransplant from previous studies. Further studies are needed to achieve bone formation similar to isotransplants. © 2014 Wiley Periodicals, Inc. Microsurgery 34:301-307, 2014. PMID:24395434

Larsen, Mikko; Willems, Wouter F; Pelzer, Michael; Friedrich, Patricia F; Dadsetan, Mahrokh; Bishop, Allen T

2014-05-01

211

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

PubMed

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

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

2014-03-01

212

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

213

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

PubMed Central

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

Shore, Eileen M.

2011-01-01

214

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.

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

2013-01-01

215

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

SciTech Connect

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

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

2012-10-23

216

Bone morphogenetic protein 2 in the early development of Xenopus laevis  

Microsoft Academic Search

The temporal and spatial transcription patterns of the Xenopus laevis Bone morphogenetic protein 2 (BMP-2) gene have been investigated. Unlike the closely related BMP-4 gene, the BMP-2 gene is strongly transcribed during oogenesis. Besides some enrichment within the animal half, maternal BMP-2 transcripts are ubiquitously distributed in the early cleavage stage embryos but rapidly decline during gastrulation. Zygotic transcription of

Joachim H. Clement; Petra Fettes; Sigrun Knöchel; Jutta Lef; Walter Knöchel

1995-01-01

217

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

218

Treatment of an early failing implant by guided bone regeneration using resorbable collagen membrane and bioactive glass  

PubMed Central

Implant failure can be divided into early (prior to prosthetic treatment) or late (after prosthetic rehabilitation). Early failure is generally due to interference in the healing process after implant placement. Implants undergoing early failure will show progressive bone loss on radiographs during the healing period (4 to 6 weeks). In the present case report, early progressive bone loss was seen at 6 weeks, after placement of a non-submerged single piece mini implant. Clinical examination revealed peri-implant bleeding on probing and pocket and grade-1 mobility. Treatment protocol included mechanical debridement (plastic curettes), chemical detoxification with supersaturated solution of citric acid, antibiotics and guided bone regeneration therapy using the collagen membrane as guided bone regeneration barrier in combination with bioactive glass as bone grafting material. The 6 month postoperative examination showed complete resolution of the osseous defect, thus suggesting that this technique may hold promise in the treatment of implants undergoing early failure.

Talreja, Prakash S.; Gayathri, G. V.; Mehta, D. S.

2013-01-01

219

Treatment of an early failing implant by guided bone regeneration using resorbable collagen membrane and bioactive glass.  

PubMed

Implant failure can be divided into early (prior to prosthetic treatment) or late (after prosthetic rehabilitation). Early failure is generally due to interference in the healing process after implant placement. Implants undergoing early failure will show progressive bone loss on radiographs during the healing period (4 to 6 weeks). In the present case report, early progressive bone loss was seen at 6 weeks, after placement of a non-submerged single piece mini implant. Clinical examination revealed peri-implant bleeding on probing and pocket and grade-1 mobility. Treatment protocol included mechanical debridement (plastic curettes), chemical detoxification with supersaturated solution of citric acid, antibiotics and guided bone regeneration therapy using the collagen membrane as guided bone regeneration barrier in combination with bioactive glass as bone grafting material. The 6 month postoperative examination showed complete resolution of the osseous defect, thus suggesting that this technique may hold promise in the treatment of implants undergoing early failure. PMID:23633789

Talreja, Prakash S; Gayathri, G V; Mehta, D S

2013-01-01

220

Bone formation following transplantation of genetically modified primary bone marrow stromal cells  

Microsoft Academic Search

Bone marrow stromal cells contain mesenchymal stem cells that can differentiate into a variety of mesenchymal tissues; in the presence of BMP-2, for example, they differentiate into osteoblasts. We constructed replication-deficient adenoviral vectors encoding human BMP-2 (BMP-2\\/Ad) or BMP-4 (BMP-4\\/Ad) and used them to transduce primary bone marrow stromal cells from the femurs of four-week-old female C3H mice, which then

Osamu Sugiyama; Hideo Orimo; Satoru Suzuki; Kazuo Yamashita; Hiromoto Ito; Takashi Shimada

2003-01-01

221

Ephrin B1 Regulates Bone Marrow Stromal Cell Differentiation and Bone Formation by Influencing TAZ Transactivation via Complex Formation with NHERF1?  

PubMed Central

Mutations of ephrin B1 in humans result in craniofrontonasal syndrome. Because little is known of the role and mechanism of action of ephrin B1 in bone, we examined the function of osteoblast-produced ephrin B1 in vivo and identified the molecular mechanism by which ephrin B1 reverse signaling regulates bone formation. Targeted deletion of the ephrin B1 gene in type 1?2 collagen-producing cells resulted in severe calvarial defects, decreased bone size, bone mineral density, and trabecular bone volume, caused by impairment in osterix expression and osteoblast differentiation. Coimmunoprecipitation of the TAZ complex with TAZ-specific antibody revealed a protein complex containing ephrin B1, PTPN13, NHERF1, and TAZ in bone marrow stromal (BMS) cells. Activation of ephrin B1 reverse signaling with soluble EphB2-Fc led to a time-dependent increase in TAZ dephosphorylation and shuttling from cytoplasm to nucleus. Treatment of BMS cells with exogenous EphB2-Fc resulted in a 4-fold increase in osterix expression as determined by Western blotting. Disruption of TAZ expression using specific lentivirus small hairpin RNA (shRNA) decreased TAZ mRNA by 80% and ephrin B1 reverse signaling-mediated increases in osterix mRNA by 75%. Knockdown of NHERF1 expression reduced basal levels of osterix expression by 90% and abolished ephrin B1-mediated induction of osterix expression. We conclude that locally produced ephrin B1 mediates its effects on osteoblast differentiation by a novel molecular mechanism in which activation of reverse signaling leads to dephosphorylation of TAZ and subsequent release of TAZ from the ephrin B1/NHERF1/TAZ complex to translocate to the nucleus to induce expression of the osterix gene and perhaps other osteoblast differentiation genes. Our findings provide strong evidence that ephrin B1 reverse signaling in osteoblasts is critical for BMS cell differentiation and bone formation.

Xing, Weirong; Kim, Jonghyun; Wergedal, Jon; Chen, Shin-Tai; Mohan, Subburaman

2010-01-01

222

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

223

Role of scaffold internal structure on in vivo bone formation in macroporous calcium phosphate bioceramics.  

PubMed

Purpose of this study was the analysis of the role of density and pore interconnection pathway in scaffolds to be used as bone substitutes. We have considered 2 hydroxyapatite bioceramics with identical microstructure and different macro-porosity, pore size distribution and pore interconnection pathway. The scaffolds were obtained with two different procedures: (a) sponge matrix embedding (scaffold A), and (b) foaming (scaffold B). Bone ingrowth within the two bioceramics was obtained using an established model of in vivo bone formation by exogenously added osteoprogenitor cells. The histological analysis of specimens at different time after in vivo implantation revealed in both materials a significant extent of bone matrix deposition. Interestingly enough, scaffold B allowed a faster occurrence of bone tissue, reaching a steady state as soon as 4 weeks. Scaffold A on the other hand reached a comparable level of bone formation only after 8 weeks of in vivo implantation. Both scaffolds were well vascularised, but larger blood vessels were observed in scaffold A. Here we show that porosity and pore interconnection of osteoconductive scaffolds can influence the overall amount of bone deposition, the pattern of blood vessels invasion and finally the kinetics of the bone neoformation process. PMID:16488007

Mastrogiacomo, Maddalena; Scaglione, Silvia; Martinetti, Roberta; Dolcini, Laura; Beltrame, Francesco; Cancedda, Ranieri; Quarto, Rodolfo

2006-06-01

224

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

PubMed

Estrogens are well known steroid hormones necessary to maintain bone health. In addition, mechanical loading, in which estrogen signaling may intersect with the Wnt/?-catenin pathway, is essential for bone maintenance. As osteocytes are known as the major mechanosensory cells embedded in mineralized bone matrix, osteocyte ER? deletion mice (ER?(?Ocy/?Ocy)) were generated by mating ER? floxed mice with Dmp1-Cre mice to determine the role of ER? in osteocytes. Trabecular bone mineral density of female, but not male ER?(?Ocy/?Ocy) mice was significantly decreased. Bone formation parameters in ER?(?Ocy/?Ocy) were significantly decreased while osteoclast parameters were unchanged. This suggests that ER? in osteocytes exerts osteoprotective function by positively controlling bone formation. To identify potential targets of ER?, gene array analysis of Dmp1-GFP osteocytes sorted by FACS from ER?(?Ocy/?Ocy) and control mice was performed. Gene expression microarray followed by gene ontology analyses revealed that osteocytes from ER?(?Ocy/?Ocy) highly expressed genes categorized in 'Secreted' when compared to control osteocytes. Among them, expression of Mdk and Sostdc1, both of which are Wnt inhibitors, was significantly increased without alteration of expression of the mature osteocyte markers such as Sost and ?-catenin. Moreover, hindlimb suspension experiments showed that trabecular bone loss due to unloading was greater in ER?(?Ocy/?Ocy) mice without cortical bone loss. These data suggest that ER? in osteocytes has osteoprotective functions in trabecular bone formation through regulating expression of Wnt antagonists, but conversely plays a negative role in cortical bone loss due to unloading. PMID:24333171

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

2014-03-01

225

Short-Term Lower-Body Plyometric Training Improves Whole Body BMC, Bone Metabolic Markers, and Physical Fitness in Early Pubertal Male Basketball Players.  

PubMed

The effects of a 9-week lower-body plyometric training program on bone mass, bone markers and physical fitness was examined in 51 early pubertal male basketball players divided randomly into a plyometric group (PG: 25 participants) and a control group (CG: 26 participants). Areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) in the whole body, L2-L4 vertebrae, and in total hip, serum levels of osteocalcin (Oc) and C-terminal telopeptide fragment of Type I collagen (CTx), jump, sprint and power abilities were assessed at baseline and 9 weeks. Group comparisons were done by independent student's t-test between means and analyses of (ANOVA) and covariance (ANCOVA), adjusting for baseline values. PG experienced a significant increase in Oc (p < .01) and all physical fitness except for the 5-jump test. However, there was no improvement in aBMD, BMC and BA in any measured site, except in whole body BMC of the PG. A positive correlation was observed between percentage increase (?%) of physical fitness and those of (Oc) for the PG. In summary, biweekly sessions of lower body plyometric training program were successful for improving whole body BMC, bone formation marker (Oc) and physical fitness in early pubertal male basketball players. PMID:24018349

Zribi, Anis; Zouch, Mohamed; Chaari, Hamada; Bouajina, Elyes; Ben Nasr, Hela; Zaouali, Monia; Tabka, Zouhair

2014-02-01

226

Short-Term Lower-Body Plyometric Training Improves Whole-Body BMC, Bone Metabolic Markers, and Physical Fitness in Early Pubertal Male Basketball Players.  

PubMed

The effects of a 9-week lower-body plyometric training program on bone mass, bone markers and physical fitness was examined in 51 early pubertal male basketball players divided randomly into a plyometric group (PG: 25 participants) and a control group (CG: 26 participants). Areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) in the whole body, L2-L4 vertebrae, and in total hip, serum levels of osteocalcin (Oc) and C-terminal telopeptide fragment of Type I collagen (CTx), jump, sprint and power abilities were assessed at baseline and 9 weeks. Group comparisons were done by independent student's t-test between means and analyses of (ANOVA) and covariance (ANCOVA), adjusting for baseline values. PG experienced a significant increase in Oc (p < .01) and all physical fitness except for the 5-jump test. However, there was no improvement in aBMD, BMC and BA in any measured site, except in whole body BMC of the PG. A positive correlation was observed between percentage increase (?%) of physical fitness and those of (Oc) for the PG. In summary, biweekly sessions of lower body plyometric training program were successful for improving whole body BMC, bone formation marker (Oc) and physical fitness in early pubertal male basketball players. PMID:24662116

Zribi, Anis; Zouch, Mohamed; Chaari, Hamada; Bouajina, Elyes; Ben Nasr, Hela; Zaouali, Monia; Tabka, Zouhair

2014-02-01

227

Palm Tocotrienol Supplementation Enhanced Bone Formation in Oestrogen-Deficient Rats  

PubMed Central

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

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

2012-01-01

228

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

PubMed Central

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

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

1997-01-01

229

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

NASA Technical Reports Server (NTRS)

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

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

1992-01-01

230

Pure siliceous ooze, a diagenetic environment for early chert formation  

NASA Astrophysics Data System (ADS)

The formation of marine opal-CT nodules or layers as early diagenetic deposits has been documented only in Antarctic deep-sea sediments. In contrast, porcellanites and cherts in land sections and Deep Sea Drilling Project and Ocean Drilling Program drill sites are usually found in sediment sections of Miocene age and older. During R.V. Polarstem cruises ANT-IX/3 and 4, young porcellanites were recovered for the first time in contact with their host sediment in two cores from the Atlantic sector of the southern ocean. Chemical and mineralogical studies of these deposits and their surrounding sediments have increased knowledge about very early chert formation. In both cores the porcellanites are embedded in sediments rich in opal-A with extremely low levels of detrital minerals, an environment that seems conducive to a rapid transformation of biogenic silica into porcellanites.

Bohrmann, Gerhard; Abelmann, Andrea; Gersonde, Rainer; Hubberten, Hans; Kuhn, Gerhard

1994-03-01

231

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

232

Engineering bone formation from human dental pulp- and periodontal ligament-derived cells.  

PubMed

A robust method for inducing bone formation from cultured dental mesenchymal cells has not been established. In this study, a method for generating bone tissue in vivo from cultured human dental pulp- and periodontal ligament-derived cells (DPCs and PDLCs, respectively) was designed using exogenous bone morphogenetic protein 2 (BMP2). DPCs and PDLCs showed enhanced alkaline phosphatase (ALP) activity and calcified nodule formation in medium containing dexamethasone, ?-glycerophosphate, and ascorbic acid (osteogenic medium). However, the addition of recombinant human bone morphogenetic protein 2 (rhBMP2) to osteogenic medium remarkably increased ALP activity and in vitro calcification above the increases observed with osteogenic medium alone. rhBMP2 also significantly upregulated the expression of osteocalcin, osteopontin, and dentin matrix protein 1 mRNA in both cell types cultured in osteogenic medium. Finally, we detected prominent bone-like tissue formation in vivo when cells had been exposed to rhBMP2 in osteogenic medium. In contrast, treatments with osteogenic medium or rhBMP2 alone could not induce abundant mineralized tissue formation. We propose here that treatment with rhBMP2 in osteogenic medium can make dental mesenchymal tissues a highly useful source of cells for bone tissue engineering. In addition, both DPCs and PDLCs showed similar and remarkable osteo-inducibility. PMID:20614244

Ikeda, Hideyoshi; Sumita, Yoshinori; Ikeda, Mihoko; Ikeda, Hisazumi; Okumura, Teruhito; Sakai, Eiko; Nishimura, Masahiro; Asahina, Izumi

2011-01-01

233

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

SciTech Connect

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

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

2006-01-01

234

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

USGS Publications Warehouse

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

Modreski, P. J.

2001-01-01

235

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

PubMed Central

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

Tatl?, Ali Murat; Goksu, Sema Sezgin; Arslan, Deniz; Bassorgun, Cumhur Ibrahim; Coskun, Hasan Senol

2013-01-01

236

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

237

CO2-SO2 clathrate hydrate formation on early Mars  

NASA Astrophysics Data System (ADS)

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

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

2013-04-01

238

Alteration of newly induced endochondral bone formation in adult mice without tumour necrosis factor receptor 1.  

PubMed

Tumour necrosis factor (TNF)-alpha, a major proinflammatory cytokine, exerts its role on bone cells through two receptors (TNFR1 and TNFR2). TNFR1, but not TNFR2, is expressed by osteoblasts and its function in bone formation in vivo is not fully understood. We compared in vivo new bone formation in TNFR1-deficient (TNFR1(-/-)) mice and wild-type mice, using two models of bone formation: intramembranous ossification following tibial marrow ablation and endochondral ossification induced by bone morphogenetic protein (BMP)-2. Intramembranous osteogenesis in TNFR1(-/-) mice did not differ from the wild-type mice either in histomorphometric parameters or mRNA expression of bone-related markers and inflammatory cytokines. During endochondral osteogenesis, TNFR1(-/-) mice formed more cartilage (at post-implantation day 9), followed by more bone and bone marrow (at day 12). mRNAs for BMP-2, -4 and -7 were increased during the endochondral differentiation sequence in TNFR1(-/-) mice. The expression of receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-kappa B (RANK), as assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR), was also increased significantly during endochondral ossification in TNFR1(-/-) mice. In conclusion, signalling through the TNFR1 seems to be a negative regulator of new tissue formation during endochondral but not intramembranous osteogenesis in an adult organism. BMPs and RANKL and its receptor RANK may be involved in the change of local environment in the absence of TNFR1 signalling. PMID:15654822

Luki?, I K; Grcevi?, D; Kovaci?, N; Katavi?, V; Ivcevi?, S; Kalajzi?, I; Marusi?, A

2005-02-01

239

Suppressive effects of Anoectochilus formosanus extract on osteoclast formation in vitro and bone resorption in vivo  

Microsoft Academic Search

Anoectochilus formosanus, a plant native to Taiwan, is used as a folk medicine. It was found that oral administration of A. formosanus extract (AFE) (500 mg\\/kg) for 4 weeks suppressed bone weight loss and trabecular bone loss in ovariectomized mice, an experimental\\u000a model of osteoporosis. Although AFE at 12.5 and 25 ?g\\/ml inhibited osteoclast formation in co-culture of osteoblasts and

Kikuko Masuda; Mayumi Ikeuchi; Tomoyuki Koyama; Kohji Yamaguchi; Je-Tae Woo; Tomio Nishimura; Kazunaga Yazawa

2008-01-01

240

The role of vitamin D in the medullary bone formation in egg-laying Japanese quail and in immature male chicks treated with sex hormones.  

PubMed

The effect of vitamin D3 on medullary bone formation was investigated in egg-laying Japanese quail and in immature male chicks treated with sex hormones. When laying quail were fed a vitamin D-deficient diet for 16 days, their eggshell weights and egg production rate were markedly reduced in a time-dependent manner with a significant decrease in plasma calcium and 25-hydroxyvitamin D3 levels. The calcium content of the medullary bone of femurs decreased markedly with the progress of vitamin D deficiency, whereas that of the cortical bone remained unchanged. Quantitative histological examination also showed that the area of the mineralized portion of medullary bone in quail that were fed the vitamin D-deficient diet markedly decreased compared with that in the control laying quail, whereas the total area of the mineralized and unmineralized portions of medullary bone in the bone marrow cavity increased moderately. Daily administration of vitamin D3 (0.75 microgram/day) to the vitamin D-deficient quail increased the mineralization of medullary bone as early as day 4. Daily administration of both estradiol (0.3 mg/day) and testosterone (0.9 mg/day) for 3 weeks to immature male chicks induced an apparent hypercalcemia and matrix formation of medullary bone, regardless of the vitamin D status of the chicks. Mineralization of medullary bone was observed only when vitamin D3 was administered together with the sex hormones. These results suggest that vitamin D3 is directly involved in the mineralization of medullary bone in birds. PMID:6311373

Takahashi, N; Shinki, T; Abe, E; Horiuchi, N; Yamaguchi, A; Yoshiki, S; Suda, T

1983-07-01

241

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

242

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.

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

2014-01-01

243

Rapid and robust response of biochemical markers of bone formation to teriparatide therapy.  

PubMed

Teriparatide, a parathyroid hormone analogue, is a potent anabolic treatment for postmenopausal osteoporosis. Studies have shown that teriparatide induces large increases in biochemical markers of bone formation after 1 month of therapy followed by a delayed increase in bone resorption markers. The aims of this study were to (1) describe changes in bone turnover markers during 28 days of treatment with teriparatide; (2) identify the earliest time point by which most subjects showed a biochemical response to teriparatide; (3) identify potential biomarkers of positive bone response; (4) describe changes in bone turnover markers 4 weeks after stopping teriparatide. We recruited 15 osteopenic postmenopausal women, ages 55-69 (mean 62) years. All received 20 microg teriparatide subcutaneously for 28 days. Serum levels of the bone formation markers type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), osteocalcin (OC), bone alkaline phosphatase (bone ALP), and the bone resorption markers crosslinked C-telopeptide of type I collagen (Sbeta-CTX), crosslinked N-telopeptide of type I collagen (S-NTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were measured on 11 occasions: three times before dosing (baseline) and on days 3, 7, 10, 14, 19, 24 and 28 and at day 56 (i.e., 28 days after stopping teriparatide ). During the first 2 days of teriparatide treatment, PINP levels increased rapidly, by 8.2% (90% confidence interval (CI) 6.9%, 9.5%) and continued to increase until the end of treatment to 110.8%. PICP and OC showed a similar, but less pronounced, pattern. All three markers increased by at least 75% at day 28. A small, transient decrease in bone resorption markers occurred over the same period. Following cessation of treatment, concentrations of bone formation markers decreased to within 20% of baseline values by day 56. In conclusion, the bone formation markers PINP, PICP and OC show a rapid and robust increase in response to teriparatide, which is noticeable during the first week of therapy. PINP is the most responsive marker. These findings have important implications for monitoring patients treated with teriparatide and may also inform the design of studies of new anabolic agents for osteoporosis. PMID:19679211

Glover, Sarah J; Eastell, Richard; McCloskey, Eugene V; Rogers, Angela; Garnero, Patrick; Lowery, Jonathan; Belleli, Rossella; Wright, Timothy M; John, Markus R

2009-12-01

244

Cellular effect of low-level laser therapy on the rate and quality of bone formation in mandibular distraction osteogenesis.  

PubMed

Abstract Objective: Therapeutic lasers have been shown to influence bone physiology and repair. The aim of the present investigation was to evaluate the use of a GaAlAs (?:810?nm) laser in distraction osteogenesis. Background data: To reduce problems associated with distraction osteogenesis and shorten the time required for treatment, it is desirable to accelerate the process of bone formation. Materials and methods: Eighteen male rabbits underwent corticotomy of mandibular body, and customized distraction devices were inserted. After a 5-day latency period, the mandibles were lengthened by 0.5?mm/day for 10 days. The rabbits were divided into two groups. A GaAlAs (?: 810?nm) laser beam with the parameters power (P), 200 mW; energy density (ED), 3?J/cm(2); time (T), 7.5 sec; power density (PD) 400 mW/cm(2); energy (E) 1.5?J and spot diameter, 0.8?mm was directed medially and laterally in the study group; the control group received no laser treatment. The exposure continued with six more doses every other day. Three rabbits from each of the two groups were euthanized on the 10th, 20th, and 40th days post-distraction (consolidation) period. Results: Both light microscopy and scanning electron microscopic (SEM) analysis showed significant improvement in new bone formation in the study group at the 10th and 20th days compared with the control group, but the difference was more prominent on the 10th day. By the 40th day, there were no significant differences between the two groups. Conclusions: This study shows that a low-level GaAlAs (?:810 nm; P, 200?mW) laser hastens new bone formation only in the early stages of the consolidation period in distraction osteogenesis, and has no significant effect in later stages. PMID:24905927

Fazilat, Farzad; Ghoreishian, Mahdi; Fekrazad, Reza; Kalhori, Katayoun A M; Khalili, Sara Dehghan; Pinheiro, Antonio Luiz Barbosa

2014-06-01

245

Systemic prostaglandin E2 increases cancellous bone formation and mass in aging rats and stimulates their bone marrow osteogenic capacity in vivo and in vitro.  

PubMed

Prostaglandin E(2) (PGE(2)) has been shown to exert a bone anabolic effect in young and adult rats. In this study we tested whether it possesses a similar effect on bone formation and bone mass in aging rats. Fifteen-month-old rats were injected daily with either PGE(2) at 5 mg/kg or vehicle for 14 days. PGE(2) treatment stimulated the rate of cancellous bone formation (a approximately 5.5-fold increase in bone formation rate), measured by the incorporation of calcein into bone-forming surfaces at the tibial proximal metaphysis. This effect resulted in increased cancellous bone area (+54%) at the same site. Since PGE(2) treatment resulted in a much higher proportion of bone surface undergoing bone formation and thus lined with osteoblasts, we tested the hypothesis that PGE(2) stimulates osteoblast differentiation from bone marrow precursor cells both in vivo and in vitro. We found that ex vivo cultures of bone marrow stromal cells from rats injected for 2 weeks with PGE(2) at 5 mg/kg per day yielded more ( approximately 4-fold) mineralized nodules and exhibited a greater (by 30-40%) alkaline phosphatase activity compared with cultures from vehicle-injected rats, attesting to a stimulation of osteoblastic differentiation by PGE(2). We also compared the osteogenic capacity of bone marrow from aging (15-month-old) versus young (5-week-old) rats and its regulation by PGE(2) in vitro. Bone marrow stromal cell cultures from aging rats exhibited a greatly diminished osteogenic capacity, reflected in reduced nodule formation ( approximately 6% of young animals) and lower alkaline phosphatase activity ( approximately 60% of young animals). However, these parameters could be stimulated in both groups of animals by incubation with 10-100 nM PGE(2). The magnitude of this stimulation was greater in cultures from aging rats (+550% vs +70% in nodule formation of aging compared with young rats). In conclusion, we demonstrate here that PGE(2) exerts a bone anabolic effect in aging rats, similar to the effect we and others have reported in young, growing rats. The PGE(2)-stimulated bone formation, which augments bone mass, most likely results from recruitment of osteoblasts from their bone marrow stromal precursors. PMID:11139777

Keila, S; Kelner, A; Weinreb, M

2001-01-01

246

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

PubMed

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

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

2010-09-20

247

Bone Turnover and Metabolism in Patients with Early Multiple Sclerosis and Prevalent Bone Mass Deficit: A Population-Based Case-Control Study  

PubMed Central

Background Low bone mass is prevalent in ambulatory multiple sclerosis (MS) patients even shortly after clinical onset. The mechanism is not known, but could involve shared etiological risk factors between MS and low bone mass such as hypovitaminosis D operating before disease onset, or increased bone loss after disease onset. The aim of this study was to explore the mechanism of the low bone mass in early-stage MS patients. Methodology/Principal Findings We performed a population-based case-control study comparing bone turnover (cross-linked N-terminal telopeptide of type 1 collagen; NTX, bone alkaline phosphatase; bALP), metabolism (25-hydroxy- and 1, 25-dihydroxyvitamin D, calcium, phosphate, and parathyroid hormone), and relevant lifestyle factors in 99 patients newly diagnosed with clinically isolated syndrome (CIS) or MS, and in 159 age, sex, and ethnicity matched controls. After adjustment for possible confounders, there were no significant differences in NTX (mean 3.3; 95% CI ?6.9, 13.5; p?=?0.519), bALP (mean 1.6; 95% CI ?0.2, 3.5; p?=?0.081), or in any of the parameters related to bone metabolism in patients compared to controls. The markers of bone turnover and metabolism were not significantly correlated with bone mass density, or associated with the presence of osteoporosis or osteopenia within or between the patient and control groups. Intake of vitamin D and calcium, reported UV exposure, and physical activity did not differ significantly. Conclusions/Significance Bone turnover and metabolism did not differ significantly in CIS and MS patients with prevalent low bone mass compared to controls. These findings indicate that the bone deficit in patients newly diagnosed with MS and CIS is not caused by recent acceleration of bone loss, and are compatible with shared etiological factors between MS and low bone mass.

Moen, Stine Marit; Celius, Elisabeth Gulowsen; Sandvik, Leiv; Brustad, Magritt; Nordsletten, Lars; Eriksen, Erik Fink; Holm?y, Trygve

2012-01-01

248

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.

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

2013-01-01

249

Acceleration of new bone formation by an electrically polarized hydroxyapatite microgranule/platelet-rich plasma composite.  

PubMed

We have developed a technology for the electrical polarization and electrical characterization of hydroxyapatite (HA) microgranules. In order to improve handling of ceramic powders to fulfill complex geometrical demands, platelet-rich plasma (PRP) containing many growth factors was chosen as a carrier of HA microgranules. In this study, the effects of this electrically polarized HA microgranule/PRP composite on new bone formation were examined. To compare osteoconductivity, HA microgranules with or without electrical polarization/PRP composite gel, HA microgranules alone with or without electrical polarization, or PRP gel were implanted into holes in the medial femoral condyles of rabbits. As a control, some of the bone holes were left empty (n=6 in each group). Histological examination was performed 3 and 6 weeks after the surgical operation. It was suggested that PRP alone could not induce new bone formation until 6 weeks after implantation. HA microgranules with or without electrical polarization/PRP composite, especially the former, activated osteogenic cells, resulting in enhanced bone formation. It was confirmed that electrical polarization treatment of HA microgranules can accelerate new bone formation, and that this effect is enhanced by forming a complex within the PRP. PMID:22510403

Ohba, Seiko; Wang, Wei; Itoh, Soichiro; Takagi, Yuzo; Nagai, Akiko; Yamashita, Kimihiro

2012-07-01

250

Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation  

PubMed Central

Perlecan (Hspg2) is a heparan sulfate proteoglycan expressed in basement membranes and cartilage. Perlecan deficiency (Hspg2?/?) in mice and humans causes lethal chondrodysplasia, which indicates that perlecan is essential for cartilage development. However, the function of perlecan in endochondral ossification is not clear. Here, we report the critical role of perlecan in VEGF signaling and angiogenesis in growth plate formation. The Hspg2?/? growth plate was significantly wider but shorter due to severely impaired endochondral bone formation. Hypertrophic chondrocytes were differentiated in Hspg2?/? growth plates; however, removal of the hypertrophic matrix and calcified cartilage was inhibited. Although the expression of MMP-13, CTGF, and VEGFA was significantly upregulated in Hspg2?/? growth plates, vascular invasion into the hypertrophic zone was impaired, which resulted in an almost complete lack of bone marrow and trabecular bone. We demonstrated that cartilage perlecan promoted activation of VEGF/VEGFR by binding to the VEGFR of endothelial cells. Expression of the perlecan transgene specific to the cartilage of Hspg2?/? mice rescued their perinatal lethality and growth plate abnormalities, and vascularization into the growth plate was restored, indicating that perlecan in the growth plate, not in endothelial cells, is critical in this process. These results suggest that perlecan in cartilage is required for activating VEGFR signaling of endothelial cells for vascular invasion and for osteoblast migration into the growth plate. Thus, perlecan in cartilage plays a critical role in endochondral bone formation by promoting angiogenesis essential for cartilage matrix remodeling and subsequent endochondral bone formation.

Ishijima, Muneaki; Suzuki, Nobuharu; Hozumi, Kentaro; Matsunobu, Tomoya; Kosaki, Keisuke; Kaneko, Haruka; Hassell, John R.; Arikawa-Hirasawa, Eri; Yamada, Yoshihiko

2012-01-01

251

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

SciTech Connect

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

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

1986-08-01

252

Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo.  

PubMed

Disuse osteoporosis is a major cause to increase the risk of fractures in bed-ridden patients whose numbers are increasing in our modern society. However, the mechanisms underlying the sensing of mechanical stress in bone are largely unknown. CIZ localizes at cell adhesion plaque and transfers into nuclear compartments and activates promoters of the genes encoding enzymes, which degrade matrix proteins to link signals from the cell adhesion site to nuclear events. We examined whether this nucleocytoplasmic shuttling protein would be involved in mediation of mechanical stress signaling. Unloading based on tail suspension reduced bone volume in wild-type mice. In contrast, CIZ-deficient mice revealed suppression in such reduction of bone mass due to unloading. Histomorphometric analysis revealed that unloading suppressed the levels of osteoblastic bone formation parameters, and such suppression of bone formation parameters was blocked by CIZ-deficiency. Osteoclastic bone resorption parameters were similar regardless of CIZ-deficiency after 2-week unloading. Mineralized nodule formation in the cultures of bone marrow cells obtained from the bone of mice subjected to unloading was suppressed in wild-type mice. CIZ deficiency blocked such reduction in nodule formation induced by unloading. These data indicated that nucleocytoplasmic shuttling protein, CIZ, plays a pivotal role in the response of bone mass in unloading condition. PMID:17301008

Hino, K; Nakamoto, T; Nifuji, A; Morinobu, M; Yamamoto, H; Ezura, Y; Noda, M

2007-04-01

253

Postnatally induced inactivation of Osterix in osteoblasts results in the reduction of bone formation and maintenance  

PubMed Central

Osterix (Osx) is a zinc-finger-containing transcription factor that is highly specific to osteoblasts in vivo. Because Osx homozygous null mutants die in the immediate perinatal period showing a complete absence of bone formation, it is impossible determine the role that Osx plays in bones that have already formed after birth. To determine whether Osx is essential for bone maintenance and homeostasis, we conditionally inactivated the Osx gene in adult bone using the Cre/loxP recombination system. In previous reports, 2.3-kb Col1a1-CreERT2 mice that expressed a Cre recombinase that is transiently inducible by 4-hydroxytamoxifen (4-OHT) were intercrossed with Rosa26R (R26R) reporter mice, which resulted in the production of Cre-expressing osteoblasts that were detected upon X-gal staining. In the present study, inducible Col1a1-CreERT2 transgenic mice and conditional Osx mice (Osxflox/+) were used to generate Osxflox/?; Col1a1-CreERT2 mice. The Osx gene in Osxflox/?; Col1a1-CreERT2 mice was inactivated in the osteoblasts of already formed bones by active Cre recombinase after the administration of 4-OHT. The bones from 4-OHT-treated Osxflox/?; Col1a1-CreERT2 mice and oil-treated control mice were analyzed by radiography, histology, and histomorphometry. Even though no significant difference was observed in the radiographic images of the whole mouse skeletons, the mineralized trabecular bone volume and number in lumbar vertebrae were remarkably reduced in 4-OHT-treated Osxflox/?; Col1a1-CreERT2 mice. In addition, the rate of bone formation and area of mineralized surface were also reduced in 4-OHT-treated Osxflox/?; Col1a1-CreERT2 mice. Osx inactivation in already formed bones during the postnatal period caused a functional defect in osteoblasts that was followed by a reduction of bone formation, even though there were no apparent differences in osteoblast proliferation and osteoclast formation. Taken together, these results indicate that Osx is required to maintain osteoblast function following adult bone maintenance.

Baek, Wook-Young; de Crombrugghe, Benoit; Kim, Jung-Eun

2014-01-01

254

Pediatric cranial vault defects: early experience with beta-tricalcium phosphate bone graft substitute.  

PubMed

Pediatric calvarial defects may result from numerous causes. Availability of bone is often limited because of the child's age, and bone substitutes may be needed to reconstruct the defects. A bone substitute composed of ultraporous beta-tricalcium phosphate (Orthovita, Malvern, PA) is an osteoconductive product successfully used in orthopedic surgery. However, its application in cranial vault reconstruction is largely unstudied. The purpose of this investigation was to determine the healing rate of bone defects with the use of this product.A retrospective review was performed of patients in whom beta-tricalcium phosphate was used. Patient population consisted of 23 patients. Mean surgical age was 35 months. Reconstructions consisted of 20 craniosynostosis corrections and 3 posttraumatic repairs. The average defect size was 37 cm (range, 4.6-210 cm). Average follow-up was 12.7 months.At 2 months, 19 (79%) of 23 patients achieved healing of their defect, defined as the absence of persistent bone gaps. Persistent areas of bone weakness occurred in 3 patients at 4 months and 2 patients at 6 months. By 9 months, only 1 patient had not healed. This patient had the largest original defect of 210 cm. Defects taking longer than 2 months to heal measured 83 cm, whereas healed defects were 32 cm. No patients required treatment for graft-related problems such as infection or exposure.Early experience with beta-tricalcium phosphate bone substitute shows good healing of pediatric calvarial vault defects by 2 months, with no graft-associated complications. It seems most effective in the repair of smaller defects less than 40 cm. PMID:20186087

Biskup, Nataliya I; Singh, Davinder J; Beals, Stephen; Joganic, Edward F; Manwaring, Kim

2010-03-01

255

Early dynamic bone-imaging as an indicator of osseous blood flow and factors affecting the uptake of /sup 99m/Tc hydroxymethylene diphosphonate in healing bone  

SciTech Connect

The authors determined the uptake of /sup 99m/Tc-labeled hydroxymethylene diphosphonate in a surgically created defect in the canine tibia with early dynamic and delayed static bone scans. The defect consisted of a cortical bone window, ten by five millimeters, centered over the middle of the tibia. The dynamic bone scans consisted of sixty one-second images of the tibia, recorded immediately after the injections of /sup 99m/Tc, and the static scans were single forty-five-minute uptake images of the tibia. These were performed and the dogs were killed at seven, fourteen, and twenty-eight days postoperatively. The dynamic scans detected the postoperative increase in tibial blood flow because the values calculated from these scans demonstrated a significant linear relationship to tibial blood flow determined with radioactive microspheres (r = 0.76, p less than 0.001). The increased uptake of 99mTc in the cortical defect that was detected with static scans was attributable not only to the increased blood flow but also to uptake by immature bone. Early dynamic bone-imaging increases the versatility of bone scintigraphy. The significant correlation between the dynamic scans and bone blood flow suggests that this non-invasive technique can provide a quantitative comparison of changes in regional blood flow in bone.

Nutton, R.W.; Fitzgerald, R.H. Jr.; Kelly, P.J.

1985-06-01

256

Alisitos Formation calcareous facies - Early Cretaceous episode of tectonic calm  

SciTech Connect

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

Suarez-Vidal, F.

1986-04-01

257

Cell swarming leads to vortex flow in early embryo formation  

NASA Astrophysics Data System (ADS)

A forming embryo can be though of as a confined region of incompressible medium. Vortex flow is observed in early embryo formation from drosophila fruit flies to mammals. The Navier-Stokes equation for fluid flow in a cavity is known to have stable vortex solutions. A model for cell motion in which cells move independently of their neighbors corresponds to high Reynolds number (Re) incompressible flow. An alternative cell-swarming model in which cells do influence their neighbors motion (through a mechanism known as contact following) corresponds to a flow model that is similar to low Re incompressible flow. Both models can potentially lead to stable vortex formation in a confined cavity. We investigate the applicability of both models to real biological systems

Balter, Ariel; Glazier, James A.

2008-03-01

258

Research on the early planet formation stages with IPE  

NASA Astrophysics Data System (ADS)

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

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

259

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

PubMed

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

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

2013-02-01

260

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

PubMed Central

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

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

2013-01-01

261

Immunological Reaction in TNF-?-Mediated Osteoclast Formation and Bone Resorption In Vitro and In Vivo  

PubMed Central

Tumor necrosis factor-? (TNF-?) is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF-? may play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF-?B ligand (RANKL) to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF-? on bone metabolism may enable the identification of therapeutic targets that can efficiently suppress bone destruction in inflammatory bone diseases. TNF-? is considered to act by directly increasing RANK expression in macrophages and by increasing RANKL in stromal cells. Inflammatory cytokines such as interleukin- (IL-) 12, IL-18, and interferon-? (IFN-?) strongly inhibit osteoclast formation. IL-12, IL-18, and IFN-? induce apoptosis in bone marrow cells treated with TNF-???in vitro, and osteoclastogenesis is inhibited by the interactions of TNF-?-induced Fas and Fas ligand induced by IL-12, IL-18, and IFN-?. This review describes and discusses the role of cells concerned with osteoclast formation and immunological reactions in TNF-?-mediated osteoclastogenesis in vitro and in vivo.

Kitaura, Hideki; Kimura, Keisuke; Ishida, Masahiko; Kohara, Haruka; Yoshimatsu, Masako; Takano-Yamamoto, Teruko

2013-01-01

262

Bone metabolism and formation of mice bred in a 2G environment  

NASA Astrophysics Data System (ADS)

The purpose of this study is to reveal the effect of chronic hypergravity exposure on the bone formation and the bone metabolism when mammals produce offspring in a 2G environment. We measured the length and width of the thighbone, the length of the pelvis, the width of the pelvic cavity and the width of the fourth cervical vertebra on the second (F2) and the third (F3) generation mice bred in a 2G environment every ten days from 20 days old to 60 days old in an experiment on bone formation. In an experiment on bone metabolism, we measured calcium and phosphorus in the bones of the F3 in the 2G group.Ratios of the thighbone length, pelvis length, pelvic cavity width, and fourth cervical vertebra width versus the body length were calculated.These ratios were higher in the 2G group than the control group during all measuring periods.Calcium and phosphorus concentrations in the thighbone and the lumbar vertebra were lower in the 2G group than in the control group. However, the calcium and phosphorus concentrations in the cervical vertebrae of the 2G group were higher. These results suggest that the influence of gravity load may vary in the bones.

Kita, S.; Iwasaki, K.; Onishi, R.; Fujisawa, M.; Kim, H.; Shibata, S.; Ito, M.

2003-10-01

263

Ectopic bone formation in mice associated with a lactic acid\\/dioxanone\\/ethylene glycol copolymer–tricalcium phosphate composite with added recombinant human bone morphogenetic protein-2  

Microsoft Academic Search

A new putty-like material with bone-inducing capacity was made by combining a block copolymer of poly d,l-lactic acid with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) and beta-tricalcium phosphate (?-TCP) powder with added recombinant human bone morphogenetic protein-2 (rhBMP-2). To optimize the material's efficacy for bone formation, we formulated the optimal composition ratio of the respective constituent that gives the

Minori Kato; Takashi Namikawa; Hidetomi Terai; Masatoshi Hoshino; Shimpei Miyamoto; Kunio Takaoka

2006-01-01

264

Low dose fibroblast growth factor-2 (FGF2) enhances bone morphogenetic protein-2 (BMP2)-induced ectopic bone formation in mice  

Microsoft Academic Search

To examine how fibroblast growth factor-2 (FGF-2) affects the BMP signaling pathway during bone morphogenetic protein-2 (BMP-2)-induced ectopic bone formation, we implanted type I collagen disks containing constant amounts of BMP-2 (5 ?g) and varying amounts of FGF-2 onto the back muscles of adult male mice. We then performed histological analyses and histomorphometry, and measured bone mineral density and radiopaque

Yukio Nakamura; Keiji Tensho; Hiroyuki Nakaya; Masashi Nawata; Takahiro Okabe; Shigeyuki Wakitani

2005-01-01

265

Ethnic Variation in Bone Turnover in Pre and Early Perimenopausal Women: Effects of Anthropometric and Lifestyle Factors  

Microsoft Academic Search

Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Little is known, however, about ethnic variation in bone turnover. We measured serum osteocalcin (OC) and urinary N-telopeptide of type I collagen (NTX) levels in 2313 pre- or early perimenopausal women who were Caucasian (n 1140), African-American (n 651), Chi- nese (n 247), or Japanese (n 275)

JOEL S. FINKELSTEIN; MARYFRAN SOWERS; GAIL A. GREENDALE; MEI-LING T. LEE; ROBERT M. NEER; JANE A. CAULEY; BRUCE ETTINGER

266

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

267

Demonstration of the capacity of nacre to induce bone formation by human osteoblasts maintained in vitro.  

PubMed

Nacre implanted in vivo in bone is osteogenic suggesting that it may possess factor(s) which stimulate bone formation. The present study was undertaken to test the hypothesis that nacre can induce mineralization by human osteoblasts in vitro. Nacre chips were placed on a layer of first passage human osteoblasts. None of the chemical inducers generally required to obtain bone formation in vitro was added to the cultures. Osteoblasts proliferated and were clearly attracted by nacre chips to which they attached. Induction of mineralization appeared preferentially in bundles of osteoblasts surrounding the nacre chips. Three-dimensional nodules were formed by a dense osteoid matrix with cuboidal osteoblasts at the periphery and osteocytic-like cells in the center. These nodules contained foci with features of mineralized structures and bone-like structures, both radiodense to X-ray. Active osteoblasts (e.m.) with abundant rough endoplasmic reticulum, extrusion of collagen fibrils and budding of vesicles were observed. Matrix vesicles induced mineral deposition. Extracellular collagen fibrils appeared cross-banded and electrodense indicating mineralization. These results demonstrate that a complete sequence of bone formation is reproduced when human osteoblasts are cultured in the presence of nacre. This model provides a new approach to study the steps of osteoblastic differentiation and the mechanisms of induction of mineralization. PMID:1440586

Lopez, E; Vidal, B; Berland, S; Camprasse, S; Camprasse, G; Silve, C

1992-01-01

268

Non-invasive monitoring of BMP-2 retention and bone formation in composites for bone tissue engineering using SPECT/CT and scintillation probes.  

PubMed

Non-invasive imaging can provide essential information for the optimization of new drug delivery-based bone regeneration strategies to repair damaged or impaired bone tissue. This study investigates the applicability of nuclear medicine and radiological techniques to monitor growth factor retention profiles and subsequent effects on bone formation. Recombinant human bone morphogenetic protein-2 (BMP-2, 6.5 microg/scaffold) was incorporated into a sustained release vehicle consisting of poly(lactic-co-glycolic acid) microspheres embedded in a poly(propylene fumarate) scaffold surrounded by a gelatin hydrogel and implanted subcutaneously and in 5-mm segmental femoral defects in 9 rats for a period of 56 days. To determine the pharmacokinetic profile, BMP-2 was radiolabeled with (125)I and the local retention of (125)I-BMP-2 was measured by single photon emission computed tomography (SPECT), scintillation probes and ex vivo scintillation analysis. Bone formation was monitored by micro-computed tomography (microCT). The scaffolds released BMP-2 in a sustained fashion over the 56-day implantation period. A good correlation between the SPECT and scintillation probe measurements was found and there were no significant differences between the non-invasive and ex-vivo counting method after 8 weeks of follow up. SPECT analysis of the total body and thyroid counts showed a limited accumulation of (125)I within the body. Ectopic bone formation was induced in the scaffolds and the femur defects healed completely. In vivo microCT imaging detected the first signs of bone formation at days 14 and 28 for the orthotopic and ectopic implants, respectively, and provided a detailed profile of the bone formation rate. Overall, this study clearly demonstrates the benefit of applying non-invasive techniques in drug delivery-based bone regeneration strategies by providing detailed and reliable profiles of the growth factor retention and bone formation at different implantation sites in a limited number of animals. PMID:19105972

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

2009-03-19

269

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

NASA Technical Reports Server (NTRS)

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

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

1985-01-01

270

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

PubMed Central

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

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

2007-01-01

271

Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.  

PubMed

Members of the TGF-beta superfamily appear to modulate mesenchymal differentiation, including the processes of cartilage and bone formation. Nothing is yet known about the function of the TGF-beta-related factor vgr-1, also called bone morphogenetic protein-6 (BMP-6), and only limited studies have been conducted on the most closely related factors BMP-5, osteogenic protein-1 (OP-1) or BMP-7, and OP-2. Because vgr-1 mRNA has been localized in hypertrophic cartilage, this factor may play a vital role in endochondral bone formation. We developed antibodies to vgr-1, and documented that vgr-1 protein was expressed in hypertrophic cartilage of mice. To further characterize the role of this protein in bone differentiation, we generated CHO cells that overexpressed recombinant murine vgr-1 protein. Western blot analysis documented that recombinant vgr-1 protein was secreted into the media and was proteolytically processed to yield the mature vgr-1 molecule. To assess the biological activity of recombinant vgr-1 in vivo, we introduced the vgr-1-expressing CHO cells directly into the subcutaneous tissue of athymic nude mice. CHO-vgr-1 cells produced localized tumors, and the continuous secretion of vgr-1 resulted in tumors with a strikingly different gross and histological appearance as compared to the parental CHO cells. The tumors of control CHO cells were hemorrhagic, necrotic, and friable, whereas the CHO-vgr-1 tumors were dense, firm, and fibrotic. In contrast with control CHO tumors, the nests of CHO-vgr-1 tumor cells were surrounded by extensive connective tissue, which contained large regions of cartilage and bone. Further analysis indicated that secretion of vgr-1 from the transfected CHO tumor cells induced the surrounding host mesenchymal cells to develop along the endochondral bone pathway. These findings suggest that endochondral bone formation. PMID:8089189

Gitelman, S E; Kobrin, M S; Ye, J Q; Lopez, A R; Lee, A; Derynck, R

1994-09-01

272

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

PubMed Central

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

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

2013-01-01

273

Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo  

PubMed Central

Members of the TGF-beta superfamily appear to modulate mesenchymal differentiation, including the processes of cartilage and bone formation. Nothing is yet known about the function of the TGF-beta- related factor vgr-1, also called bone morphogenetic protein-6 (BMP-6), and only limited studies have been conducted on the most closely related factors BMP-5, osteogenic protein-1 (OP-1) or BMP-7, and OP-2. Because vgr-1 mRNA has been localized in hypertrophic cartilage, this factor may play a vital role in endochondral bone formation. We developed antibodies to vgr-1, and documented that vgr-1 protein was expressed in hypertrophic cartilage of mice. To further characterize the role of this protein in bone differentiation, we generated CHO cells that overexpressed recombinant murine vgr-1 protein. Western blot analysis documented that recombinant vgr-1 protein was secreted into the media and was proteolytically processed to yield the mature vgr-1 molecule. To assess the biological activity of recombinant vgr-1 in vivo, we introduced the vgr-1-expressing CHO cells directly into the subcutaneous tissue of athymic nude mice. CHO-vgr-1 cells produced localized tumors, and the continuous secretion of vgr-1 resulted in tumors with a strikingly different gross and histological appearance as compared to the parental CHO cells. The tumors of control CHO cells were hemorrhagic, necrotic, and friable, whereas the CHO-vgr-1 tumors were dense, firm, and fibrotic. In contrast with control CHO tumors, the nests of CHO-vgr-1 tumor cells were surrounded by extensive connective tissue, which contained large regions of cartilage and bone. Further analysis indicated that secretion of vgr-1 from the transfected CHO tumor cells induced the surrounding host mesenchymal cells to develop along the endochondral bone pathway. These findings suggest that endochondral bone formation.

1994-01-01

274

Biomolecule formation by oceanic impacts on early Earth  

NASA Astrophysics Data System (ADS)

Intense impacts of extraterrestrial objects melted the embryonic Earth, forming an inorganic body with a carbon-dioxide- and nitrogen-rich atmosphere. Certain simple organic molecules have been shown to form under conditions resembling meteorite impacts, although the link between these events and the development of more complex molecules remains unclear. Ordinary chondrites, the most common type of meteorite, contain solid carbon, iron and nickel-elements essential to the formation of organic chemicals. Here we use shock experiments to recreate the conditions surrounding the impact of chondritic meteorites into an early ocean. We used a propellant gun to create a high-velocity impact into a mixture of solid carbon, iron, nickel, water and nitrogen. After the impact, we recovered numerous organic molecules, including fatty acids, amines and an amino acid. We suggest that organic molecules on the early Earth may have arisen from such impact syntheses. As the natural impacts that were frequent on the early Earth are more sustained and reach higher pressures than our experiments, they may have resulted in the synthesis of a greater abundance, variety and complexity of organic compounds.

Furukawa, Yoshihiro; Sekine, Toshimori; Oba, Masahiro; Kakegawa, Takeshi; Nakazawa, Hiromoto

2009-01-01

275

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

PubMed Central

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

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

1999-01-01

276

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

PubMed

The molecular mechanisms controlling bone extracellular matrix (ECM) deposition by differentiated osteoblasts in postnatal life, called hereafter bone formation, are unknown. This contrasts with the growing knowledge about the genetic control of osteoblast differentiation during embryonic development. Cbfa1, a transcriptional activator of osteoblast differentiation during embryonic development, is also expressed in differentiated osteoblasts postnatally. The perinatal lethality occurring in Cbfa1-deficient mice has prevented so far the study of its function after birth. To determine if Cbfa1 plays a role during bone formation we generated transgenic mice overexpressing Cbfa1 DNA-binding domain (DeltaCbfa1) in differentiated osteoblasts only postnatally. DeltaCbfa1 has a higher affinity for DNA than Cbfa1 itself, has no transcriptional activity on its own, and can act in a dominant-negative manner in DNA cotransfection assays. DeltaCbfa1-expressing mice have a normal skeleton at birth but develop an osteopenic phenotype thereafter. Dynamic histomorphometric studies show that this phenotype is caused by a major decrease in the bone formation rate in the face of a normal number of osteoblasts thus indicating that once osteoblasts are differentiated Cbfa1 regulates their function. Molecular analyses reveal that the expression of the genes expressed in osteoblasts and encoding bone ECM proteins is nearly abolished in transgenic mice, and ex vivo assays demonstrated that DeltaCbfa1-expressing osteoblasts were less active than wild-type osteoblasts. We also show that Cbfa1 regulates positively the activity of its own promoter, which has the highest affinity Cbfa1-binding sites characterized. This study demonstrates that beyond its differentiation function Cbfa1 is the first transcriptional activator of bone formation identified to date and illustrates that developmentally important genes control physiological processes postnatally. PMID:10215629

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

1999-04-15

277

The primary function of gp130 signaling in osteoblasts is to maintain bone formation and strength, rather than promote osteoclast formation.  

PubMed

Interleukin-6 (IL-6) family cytokines act via gp130 in the osteoblast lineage to stimulate the formation of osteoclasts (bone resorbing cells) and the activity of osteoblasts (bone forming cells), and to inhibit expression of the osteocyte protein, sclerostin. We report here that a profound reduction in trabecular bone mass occurs both when gp130 is deleted in the entire osteoblast lineage (Osx1Cre gp130 f/f) and when this deletion is restricted to osteocytes (DMP1Cre gp130 f/f). This was caused not by an alteration in osteoclastogenesis, but by a low level of bone formation specific to the trabecular compartment. In contrast, cortical diameter increased to maintain ultimate bone strength, despite a reduction in collagen type 1 production. We conclude that osteocytic gp130 signaling is required for normal trabecular bone mass and proper cortical bone composition. PMID:24339143

Johnson, Rachelle W; Brennan, Holly J; Vrahnas, Christina; Poulton, Ingrid J; McGregor, Narelle E; Standal, Therese; Walker, Emma C; Koh, Thuan-Tzen; Nguyen, Huynh; Walsh, Nicole C; Forwood, Mark R; Martin, T John; Sims, Natalie A

2014-06-01

278

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

PubMed

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

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

2012-01-01

279

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

Microsoft Academic Search

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

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

280

The in vivo bone formation by mesenchymal stem cells in zein scaffolds  

Microsoft Academic Search

In our previous study, a three-dimensional zein porous scaffold was prepared. This scaffold showed proper mechanical properties, good biocompatibility, and controllable biodegradation. In addition, it allowed blood vessels to form inside in vivo. In the current study, we prepared the complexes of zein scaffolds and rabbit MSCs, and investigated ectopic bone formation in nude mice. Furthermore, we implanted them into

Jinwen Tu; Huajie Wang; Huiwu Li; Kerong Dai; Jinye Wang; Xiaoling Zhang

2009-01-01

281

Marrow development and its relationship to bone formation in vivo: A histological study using an implantable titanium device in rabbits  

Microsoft Academic Search

During embryogenesis, the creation of marrow sinusoids is intimately related to the coupled processes of osteogenesis and osteoclastic resorption. We set out to further define the relationship between bone formation and marrow development by implanting an intraosseous titanium device into the tibiae of rabbits which permits the examination of bone formation under standardized and reproducible conditions as well as allowing

H. Zhou; P. F. M. Choong; S. Henderson; S. T. Chou; P. Aspenberg; T. J. Martin; K. W. Ng

1995-01-01

282

New bone formation in a bone defect associated to dental implant using absorbable or non-absorbable membrane in a dog model  

PubMed Central

The aim of this research was to determine the bone formation capacity in fenestration defects associated with dental implants using absorbable and non-absorbable membranes. Six dogs were used in the study. In both tibias of each animal 3 implants were installed, and around these 5 mm circular defects were created. The defects were covered with absorbable membranes (experimental group 1), non-absorbable membranes (experimental group 2), and the third defect was not covered (control group). At 3 and 8 weeks post-surgery, the animals were euthanized and the membranes with the bone tissue around the implants were processed for histological analysis. The statistical analysis was conducted with Tukey’s test, considering statistical significance when p<0.1. Adequate bone repair was observed in the membrane-covered defects. At 3 weeks, organization of the tissue, bone formation from the periphery of the defect and the absence of inflammatory infiltrate were observed in both experimental groups, but the defect covered with absorbable membrane presented statistically greater bone formation. At 8 weeks, both membrane-covered defects showed adequate bone formation without significant differences, although they did in fact present differences with the control defect in both periods (p>0.1). In the defects without membrane, continuous connective tissue invasions and bone repair deficiency were observed. There were no significant differences in the characteristics and volume of the neoformed bone in the defects around the implants covered by the different membranes, whereas the control defects produced significantly less bone. The use of biological membranes contributes to bone formation in three-wall defects.

Lopez, Maria de Almeida; Olate, Sergio; Lanata-Flores, Antonio; Pozzer, Leandro; Cavalieri-Pereira, Lucas; Cantin, Mario; Vasquez, Belgica; de Albergaria-Barbosa, Jose

2013-01-01

283

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

PubMed

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

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

2013-11-01

284

Impact of Early Colonizers on In Vitro Subgingival Biofilm Formation  

PubMed Central

The aim of this study was to investigate the impact of early colonizing species on the structure and the composition of the bacterial community developing in a subgingival 10-species biofilm model system. The model included Streptococcus oralis, Streptococcus anginosus, Actinomycesoris, Fusobacterium nucleatum subsp. nucleatum, Veillonella dispar, Campylobacter rectus, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Based on literature, we considered Streptococcus oralis, Streptococcus anginosus, and Actinomyces oris as early colonizers and examined their role in the biofilms by either a delayed addition to the consortium, or by not inoculating at all the biofilms with these species. We quantitatively evaluated the resulting biofilms by real-time quantitative PCR and further compared the structures using confocal laser scanning microscopy following fluorescence in situ hybridisation. The absence of the early colonizers did not hinder biofilm formation. The biofilms reached the same total counts and developed to normal thickness. However, quantitative shifts in the abundances of individual species were observed. In the absence of streptococci, the overall biofilm structure appeared looser and more dispersed. Moreover, besides a significant increase of P. intermedia and a decrease of P. gingivalis , P. intermedia appeared to form filamented long chains that resembled streptococci. A. oris, although growing to significantly higher abundance in absence of streptococci, did not have a visible impact on the biofilms. Hence, in the absence of the early colonizers, there is a pronounced effect on P. intermedia and P. gingivalis that may cause distinct shifts in the structure of the biofilm. Streptococci possibly facilitate the establishment of P. gingivalis into subgingival biofilms, while in their absence P. intermedia became more dominant and forms elongated chains.

Ammann, Thomas W.; Belibasakis, Georgios N.; Thurnheer, Thomas

2013-01-01

285

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

PubMed Central

To test if ephrin B1 overexpression enhances bone mass, we generated transgenic mice overexpressing ephrin B1 under the control of a 3.6 kb rat collagen 1A1 promoter (Col3.6-Tgefnb1). Col3.6-Tgefnb1 mice express 6-, 12- and 14-fold greater levels of full-length ephrin B1 protein in bone marrow stromal cells, calvarial osteoblasts, and osteoclasts, respectively. The long bones of both genders of Col3.6-Tgefnb1 mice have increased trabecular bone volume, trabecular number, and trabecular thickness and decreased trabecular separation. Enhanced bone formation and decreased bone resorption contributed to this increase in trabecular bone mass in Col3.6-Tgefnb1 mice. Consistent with these findings, our in vitro studies showed that overexpression of ephrin B1 increased osteoblast differentiation and mineralization, osterix and collagen 1A1 expression in bone marrow stromal cells. Interaction of ephrin B1 with soluble clustered EphB2-Fc decreased osteoclast precursor differentiation into multinucleated cells. Furthermore, we demonstrated that the mechanical loading-induced increase in EphB2 expression and newly formed bone were significantly greater in the Col3.6-Tgefnb1 mice than in WT littermate controls. Our findings that overexpression of ephrin B1 in bone cells enhances bone mass and promotes a skeletal anabolic response to mechanical loading suggest that manipulation of ephrin B1 actions in bone may provide a means to sensitize the skeleton to mechanical strain to stimulate new bone formation.

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

2013-01-01

286

Prenatal and early postnatal stress exposure influences long bone length in adult rat offspring  

PubMed Central

Stress during the prenatal and early postnatal periods (perinatal stress, PS) is known to impact offspring cognitive, behavioral, and physical development, but effects on skeletal growth are not clear. Our objective was to analyze effects of variable, mild, daily PS exposure on adult offspring long bone length. Twelve pregnant rat dams were randomly assigned to receive variable stress from gestational days 14-21 (Prenatal group), postpartum days 2-9 (Postnatal), both periods (Pre-Post), or no stress (Control). Differences in adult offspring tibia and femur length were analyzed among treatment groups. Mean tibia length differed among groups for males (p=0.016) and females (p=0.009), and differences for femur length approached significance for males (p=0.051). Long bone length was shorter among PS-exposed offspring, especially those exposed to postnatal stress (Postnatal and Pre-Post groups). Results persisted when controlling for nose-tail length. These differences might reflect early stunting that is maintained in adulthood, or delayed growth among PS-exposed offspring. This study suggests that PS results in shorter long bones in adulthood, independently of effects on overall body size. Stunting and growth retardation are major global health burdens. Our study adds to a growing body of evidence suggesting that PS is a risk factor for poor linear growth.

Dancause, Kelsey Needham; Cao, Xiu Jing; Veru, Franz; Xu, Susan; Long, Hong; Yu, Chunbo; Laplante, David P.; Walker, Claire Dominique; King, Suzanne

2012-01-01

287

Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice.  

PubMed

Effective osteoporosis therapy requires agents that increase the amount and/or quality of bone. Any modification of osteoclast-mediated bone resorption by disease or drug treatment, however, elicits a parallel change in osteoblast-mediated bone formation because the processes are tightly coupled. Anabolic approaches now focus on uncoupling osteoblast action from osteoclast formation, for example, by inhibiting sclerostin, an inhibitor of bone formation that does not influence osteoclast differentiation. Here, we report that oncostatin M (OSM) is produced by osteoblasts and osteocytes in mouse bone and that it has distinct effects when acting through 2 different receptors, OSM receptor (OSMR) and leukemia inhibitory factor receptor (LIFR). Specifically, mouse OSM (mOSM) inhibited sclerostin production in a stromal cell line and in primary murine osteoblast cultures by acting through LIFR. In contrast, when acting through OSMR, mOSM stimulated RANKL production and osteoclast formation. A key role for OSMR in bone turnover was confirmed by the osteopetrotic phenotype of mice lacking OSMR. Furthermore, in contrast to the accepted model, in which mOSM acts only through OSMR, mOSM inhibited sclerostin expression in Osmr-/- osteoblasts and enhanced bone formation in vivo. These data reveal what we believe to be a novel pathway by which bone formation can be stimulated independently of bone resorption and provide new insights into OSMR and LIFR signaling that are relevant to other medical conditions, including cardiovascular and neurodegenerative diseases and cancer. PMID:20051625

Walker, Emma C; McGregor, Narelle E; Poulton, Ingrid J; Solano, Melissa; Pompolo, Sueli; Fernandes, Tania J; Constable, Matthew J; Nicholson, Geoff C; Zhang, Jian-Guo; Nicola, Nicos A; Gillespie, Matthew T; Martin, T John; Sims, Natalie A

2010-02-01

288

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

PubMed Central

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

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

2012-01-01

289

The effect of heparan sulfate application on bone formation during distraction osteogenesis.  

PubMed

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

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

2013-01-01

290

Detection of gentamicin emission from bone cement in the early postoperative period following total hip arthroplasty.  

PubMed

This article describes the characteristics of gentamicin emission from the bone cement-antibiotic complex in the early postoperative period following total hip arthroplasty. Gentamicin levels of the drain fluid taken at 6, 24, and 48 hours postoperatively were measured with a fluorescent polarization immunoassay method. Mean gentamicin concentrations were 2.6, 1.2, and 0.6 mcg/mL, respectively. Age, sex, and body mass index had no significant influence on the outcome. Results showed that the amount of gentamicin in the wound fluid is inversely proportional to the total amount excreted. Twenty-four hours postoperatively, the average gentamicin concentrations in the drain fluid taken from around the endoprosthesis implanted with Palacos-R bone cement (Zimmer Warsaw, Ind), diminished, yet remained above the minimal inhibitory concentration level. PMID:16729744

Bálint, Lehel; Koós, Zoltán; Horváth, Gábor; Szabó, György

2006-05-01

291

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

PubMed Central

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

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

2013-01-01

292

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation  

PubMed Central

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

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

2012-01-01

293

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

294

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

SciTech Connect

A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs. 33 refs., 6 figs., 1 tab.

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

1995-03-24

295

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.

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

2013-01-01

296

Bone formation in polymeric scaffolds evaluated by proton magnetic resonance microscopy and X-ray microtomography.  

PubMed

Magnetic resonance microscopy (MRM) and X-ray microtomography (XMT) were used to investigate de novo bone formation in porous poly(ethyl methacrylate) (PEMA) scaffolds, prepared by a novel co-extrusion process. PEMA scaffolds were seeded with primary chick calvarial osteoblasts and cultured under static conditions for up to 8 weeks. Bone formation within porous PEMA scaffolds was confirmed by the application of histologic stains to intact PEMA disks. Disks were treated with Alizarin red to visualize calcium deposits and with Sirius red to visualize regions of collagen deposition. DNA analysis confirmed that cells reached confluence on the scaffolds after 7 weeks in static culture. The formation of bone in PEMA scaffolds was investigated with water proton MRM. Quantitative MRM maps of the magnetization transfer ratio (MTR) yielded maps of protein deposition, and magnetic resonance (MR) relaxation times (T1 and T2) yielded maps of mineral deposition. The location of newly formed bone and local mineral concentrations were confirmed by XMT. By comparing MRM and XMT data from selected regions-of-interest in one sample, the inverse relationship between the MR relaxation times and mineral concentration was validated, and calibration curves for estimating the mineral content of cell-seeded PEMA scaffolds from quantitative MRM images were developed. PMID:15162416

Washburn, Newell R; Weir, Michael; Anderson, Paul; Potter, Kimberlee

2004-06-15

297

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

SciTech Connect

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

Marie, P.J.; Hott, M.; Perheentupa, J. (Institut National de la Sante et de la Recherche Medicale, Paris (France))

1990-02-01

298

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

299

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

300

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

SciTech Connect

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

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

1987-12-01

301

STAR FORMATION SIGNATURES IN OPTICALLY QUIESCENT EARLY-TYPE GALAXIES  

SciTech Connect

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

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

2010-05-10

302

Star Formation Signatures in Optically Quiescent Early-type Galaxies  

NASA Astrophysics Data System (ADS)

In recent years, an argument has been made that a high fraction of early-type galaxies (ETGs) in the local universe experience low levels (lsim1 M sun yr-1) of star formation (SF) that causes strong excess in UV flux, yet leaves the optical colors red. Many of these studies were based on Galaxy Evolution Explorer imaging of Sloan Digital Sky Survey (SDSS) galaxies (z ~ 0.1), and were thus limited by its 5'' FWHM. Poor UV resolution left other possibilities for UV excess open, such as the old populations or an active galactic nucleus (AGN). Here, we study high-resolution far-ultraviolet HST/ACS images of optically quiescent early-type galaxies with strong UV excess. The new images show that three-quarters of these moderately massive (~5 × 1010 M sun) ETGs shows clear evidence of extended SF, usually in form of wide or concentric UV rings, and in some cases, striking spiral arms. SDSS spectra probably miss these features due to small fiber size. UV-excess ETGs have on average less dust and larger UV sizes (D > 40 kpc) than other green-valley galaxies, which argues for an external origin for the gas that is driving the SF. Thus, most of these galaxies appear "rejuvenated" (e.g., through minor gas-rich mergers or intergalactic medium accretion). For a smaller subset of the sample, the declining SF (from the original internal gas) cannot be ruled out. SF is rare in very massive early-types (M * > 1011 M sun), a possible consequence of AGN feedback. In addition to extended UV emission, many galaxies show a compact central source, which may be a weak, optically inconspicuous AGN.

Salim, Samir; Rich, R. Michael

2010-05-01

303

Magnetic fields during the early phase of massive star formation  

NASA Astrophysics Data System (ADS)

The goal of this work is to improve our current understanding of the formation process of massive stars in the presence of magnetic fields by means of numerical simulations. In particular, I focus on protostellar accretion rates, the evolution and the properties of protostellar discs and their associated outflows, and the interplay of turbulence and magnetic fields and its impact on protostellar disc formation. In a systematic parameter study I show that the accretion rates are remarkably constant over a wide range of initial conditions. Furthermore, I show that in the absence of turbulence for strong initial magnetic fields only sub-Keplerian discs can form which is attributed to the strong magnetic braking effect. This result seems to be in contrast to observational results. The morphology of the outflows, which shows a strong dependence on the initial conditions, can ultimately be linked to the structure of the underlying disc. Well-collimated outflows with high outflows velocities only develop if a Keplerian protostellar disc is present, otherwise slowly expanding, sphere-like outflows develop. Furthermore, I analyse the driving mechanism of outflows with an analytical criterion derived in the course of this work. When including supersonic, turbulent motions in the simulations, Keplerian protostellar discs form in contrast to the non-turbulent simulations. This result is in agreement with observations of early-type protostellar objects.

Seifried, Daniel Jürgen

2013-01-01

304

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

NASA Astrophysics Data System (ADS)

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

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

2013-11-01

305

The Dose of Growth Factors Influences the Synergistic Effect of Vascular Endothelial Growth Factor on Bone Morphogenetic Protein 4-Induced Ectopic Bone Formation  

PubMed Central

Although vascular endothelial growth factor (VEGF) has been shown to act synergistically with bone morphogenetic protein (BMP)2 and BMP4 to promote ectopic endochondral bone formation via cell-based BMP gene therapy, the optimal ratio of VEGF to either of the BMPs required to obtain this beneficial effect remains unclear. In the current study, two cell types (C2C12, NIH/3T3) were retrovirally transduced to express BMP4 only or both BMP4 and VEGF. The resulting groups of cells were tested for their cellular proliferation, in vitro mineralization capacity, survival potential, and ability to undergo ectopic bone formation when implanted into a gluteofemoral muscle pocket created in severe combined immunodeficient mice. Results showed that VEGF inhibited the in vitro calcification of C2C12 and NIH/3T3 cells transduced to express BMP4. In vivo, C2C12 and NIH/3T3 cells expressing BMP4 and VEGF displayed significantly less bone formation than the same cells expressing only BMP4. In vivo, our results indicated that, when the ratio of VEGF to BMP4 is high, a detrimental effect on ectopic bone formation is observed; however, when the ratio is kept low and constant over time, the detrimental effect that VEGF has on ectopic bone formation is lost. Our studies revealed that VEGF's synergistic role in BMP4 induced ectopic bone formation is dose and cell-type dependent, which is an important consideration for cell-based gene therapy and tissue engineering for bone healing.

Li, Guangheng; Corsi-Payne, Karin; Zheng, Bo; Usas, Arvydas; Peng, Hairong

2009-01-01

306

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

307

Immobilization hypercalcaemia due to low bone formation and responding to intravenous sodium sulphate.  

PubMed Central

A young man developed acute renal failure and hypercalcaemia following severe burns. The hypercalcaemia was initially controlled by haemodialysis, but it persisted after return of renal function. Plasma PTH was inappropriately elevated, but the nephrogenous cyclic adenosine monophosphate level was low; thus the PTH was probably not biologically active, and may have been artefactually elevated by the moderate renal impairment. Bone histology, showed a normal resorbing surface, but a zero forming surface, implying that the bone dissolution leading to hypercalcaemia resulted from a failure of bone formation. Because of widespread infection and impaired renal function, the hypercalcaemia could not be treated by corticosteroid drugs, mithramycin or phosphate, and there was no response to salmon calcitonin. He was therefore treated with intravenous sodium sulphate, which increased urinary calcium excretion and reduced the plasma calcium. Sodium sulphate still has a role in the treatment of patients with hypercalcaemia. Images Figure 3

Evans, R. A.; Lawrence, P. J.; Thanakrishnan, G.; Hills, E.; Wong, S. Y.; Dunstan, C. R.

1986-01-01

308

Human bone tissue formation in diffusion chamber culture in vivo by bone-derived cells and marrow stromal fibroblastic cells.  

PubMed

Direct grafts of human cells into immunocompromised or cortisone-treated animals, either alone or within carrier materials, have been used with some success to assess the developmental capability of the grafted cells. However, identification of the donor or host origins of the generated tissue in such direct grafts is essential. In an alternative and extensively used experimental system, cells are cultured within the isolated environments of diffusion chambers, which are surgically implanted in appropriate hosts. This system allows the direct study of the cellular potentials for differentiation as host tissues are excluded. In the present study, human osteoprogenitor cell populations derived from trabecular bone explants or marrow suspensions of 3 patients (2 females aged 14 years and 1 male aged 27 years) were cultured in the absence or the continuous presence of dexamethasone (10 nmol/L). Cells were impregnated into porous hydroxyapatite ceramics before subcutaneous implantation, or placed within diffusion chambers before intraperitoneal implantation, in athymic mice. All subcutaneous implants of cells in ceramic showed morphological evidence for the formation of bone tissue. In the diffusion chambers it was found that both marrow- and bone-derived fibroblastic cells cultured in the absence of dexamethasone generally produced fibrous tissue only. When cultured in the continuous presence of dexamethasone (10 nmol/L), these cell populations produced similar osteogenic tissues with active osteoblasts, wide osteoid seams, and mineralized tissue, with cartilage toward the interior of the chamber. These results validate the diffusion chamber as an experimental system to study human osteogenesis using appropriately primed cell populations. PMID:7669435

Gundle, R; Joyner, C J; Triffitt, J T

1995-06-01

309

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

PubMed

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

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

2010-05-01

310

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.

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

2013-01-01

311

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.

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

2014-01-01

312

Erythropoietin Mediated Bone Formation Is Regulated by mTOR Signaling  

PubMed Central

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

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

2011-01-01

313

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

314

Bone metastasis from early gastric cancer following non-curative endoscopic submucosal dissection.  

PubMed

A 67-year-old male underwent endoscopic submucosal dissection (ESD) to treat early gastric cancer (EGC) in 2001. The lesion (50 mm × 25 mm diameter) was histologically diagnosed as poorly differentiated adenocarcinoma, with an ulcer finding. Although the tumor was confined to the mucosa with no evidence of lymphovascular involvement, the ESD was regarded as a non-curative resection due to the histological type, tumor size, and existence of an ulcer finding (as indicated by the 2010 Japanese gastric cancer treatment guidelines, ver. 3). Despite strong recommendation for subsequent gastrectomy, the patient refused surgery. An alternative follow-up routine was designed, which included five years of biannual clinical examinations to detect and measure serum tumor markers and perform visual assessment of recurrence by endoscopy and computed tomography scan after which the examinations were performed annually. The patient's condition remained stable for eight years, until a complaint of back pain in 2010 prompted further clinical investigation. Bone scintigraphy indicated increased uptake. Histological examination of biopsy specimens taken from the lumbar spine revealed adenocarcinoma resembling the carcinoma cells from the EGC that had been treated previously by ESD, and which was consistent with immunohistochemical findings of gastrointestinal tract cancer. Thus, the diagnosis of bone metastasis from EGC was made. The reported rates of EGC recurrence in surgically resected cases range 1.4%-3.4%, but among these bone metastasis is very rare. To our knowledge, this is the first reported case of bone metastasis from EGC following a non-curative ESD and occurring after an eight-year disease-free interval. PMID:23946610

Kawabata, Hiroyuki; Oda, Ichiro; Suzuki, Haruhisa; Nonaka, Satoru; Yoshinaga, Shigetaka; Katai, Hitoshi; Taniguchi, Hirokazu; Kushima, Ryoji; Saito, Yutaka

2013-08-14

315

Bone-like apatite layer formation on hydroxyapatite prepared by spark plasma sintering (SPS)  

Microsoft Academic Search

Hydroxyapatite (HA) compacts with high density and superior mechanical properties were fabricated by spark plasma sintering (SPS) using spray-dried HA powders as feedstock. The formation of bone-like apatite layer on SPS consolidated HA compacts were investigated by soaking the HA compacts in simulated body fluid (SBF) for various periods (maximum of 28 days). The structural changes in HA post-SBF were

Y. W. Gu; K. A. Khor; P. Cheang

2004-01-01

316

Effect of icariin on bone formation during distraction osteogenesis in the rabbit mandible  

Microsoft Academic Search

The aim of this study was to evaluate the effect of icariin on bone formation during mandibular distraction. 40 Rabbits were randomly divided into experimental and control groups. Mandibular distraction was performed 5 days after unilateral mandibular osteotomy using a custom-made external distractor at a rate of 0.5mm\\/12h for 10 days. From the first day of distraction, icariin (2.5mg\\/kg·day) was

H. Wei; L. Zili; C. Yuanlu; Y. Biao; L. Cheng; W. Xiaoxia; L. Yang; W. Xing

2011-01-01

317

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

PubMed

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

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

2013-09-01

318

Microstructural investigation of the early external callus after diaphyseal fractures of human long bone.  

PubMed

Microstructures of the early external callus after diaphyseal fractures of human long bone were investigated by using scanning electron microscopy, X-ray diffraction, and transmission electron microscopy. It was found that the main structural framework of the human early callus consists of disordered, mineralized collagen fibrils with a small fraction of regions of ordered collagen fibrils. X-ray diffraction analyses show that hydroxyapatite containing some carbonate impurity has been the dominant crystalline phase in the human early callus. In addition, a small amount of brushite phase was detected. Selected area diffraction analyses indicated that hydroxyapatite microcrystals were embedded in microfibrils with a diameter of 4.5 nm and well-banded fibrils, whereas brushite particles of 15-20 nm in an irregular shape were located in the noncollagenous organic matter around the nonmineralized, ordered collagen fibrils. The spatial distribution of the brushite particles in the human early callus was for the first time determined. The brushite particles probably serve as the reservoir of calcium and phosphate ions for subsequent mineralized periods rather than the precursor of hydroxyapatite. PMID:7612396

Wen, H B; Cui, F Z; Feng, Q L; Li, H D; Zhu, X D

1995-01-01

319

Effect of aging on bone formation induced by recombinant human bone morphogenetic protein-2 combined with fibrous collagen membranes at subperiosteal sites.  

PubMed

This study was designed to examine the effect of aging on bone formation induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a fibrous collagen membrane (FCM). Implantation was done subperiosteally in bilateral palatal grooves in 34 male Wistar rats divided into three age groups: a 10-week-old group (10w group), a 30-week-old group (30w group) and a 70-week-old group (70w group). RhBMP-2-combined FCMs were implanted on the left palatal grooves as BMP-implanted sites (BMP site), while rhBMP-2 was not implanted on the right palatal grooves as control sites. The rats were sacrificed 6 weeks after implantation, and histometric evaluations were performed. New bone formation was observed in every site of each age group and the new bone was almost completely continuous with the original bone. The new bone volume (NBV) of the BMP site was significantly higher than that of the control site in each age group. The NBV of both the control and BMP sites were highest in the 10w group and lowest in the 70w group. The disparity of NBV between the control and BMP sites, which indicated the response to implanted BMP excluding the effect of skeletal growth and surgical stimulation, did not significantly differ among the age groups. These results indicate that rhBMP-2-combined FCM has the ability to induce new bone formation continuous with original bone even in senescent rats. Furthermore, it appeared that, in the case of palatal subperiosteal implantation, the responsiveness to implanted BMP was independent of age, although the total volume of newly formed bone declined with aging. PMID:11453116

Matsumoto, A; Yamaji, K; Kawanami, M; Kato, H

2001-06-01

320

Osterix is required for cranial neural crest-derived craniofacial bone formation  

PubMed Central

Osx plays essential roles in regulating osteoblast and chondrocyte differentiation, and bone formation during mouse skeletal development. However, many questions remain regarding the requirement for Osx in different cell lineages. In this study, we asked whether Osx is required for craniofacial bone formation derived from cranial neural crest (CNC) cells. The Osx gene was conditionally inactivated in CNC-derived cells using a Wnt1-Cre recombination system. Neural crest-specific inactivation of Osx resulted in the complete absence of intramembranous skeletal elements derived from the CNC, and CNC-derived endochondral skeletal elements were also affected by Osx inactivation. Interestingly, Osx inactivated CNC-derived cells, which were recapitulated by lacZ expression, occupied the same regions of craniofacial skeletal elements as observed for controls. However, cells lost their osteogenic ability to differentiate into functional osteoblasts by Osx inactivation. These results suggest that Osx is important for craniofacial bone formation by CNC-derived cells. This finding provides novel insights of the regulation of craniofacial development by the gene network and transcription factors, and the understanding of human diseases caused by neural crest developmental abnormalities.

Baek, Wook-Young; Kim, Young-Ji; de Crombrugghe, Benoit; Kim, Jung-Eun

2014-01-01

321

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

PubMed Central

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

2012-01-01

322

Ectopic bone formation using an injectable biphasic calcium phosphate\\/Si-HPMC hydrogel composite loaded with undifferentiated bone marrow stromal cells  

Microsoft Academic Search

We have used a new synthetic injectable composite constituted of hydroxyapatite\\/tricalcium phosphate (HA\\/TCP) particles in suspension in a self-hardening Si–hydroxypropylmethylcellulose (HPMC) hydrogel. The aim of this study was to evaluate in vivo the biocompatibility and the new bone formation efficacy of this scaffold loaded with undifferentiated bone marrow stromal cells (BMSCs). This biomaterial was mixed extemporaneously with BMSCs prepared from

Christophe Trojani; Florian Boukhechba; Jean-Claude Scimeca; Fanny Vandenbos; Jean-François Michiels; Guy Daculsi; Pascal Boileau; Pierre Weiss; Georges F. Carle; Nathalie Rochet

2006-01-01

323

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

Microsoft Academic Search

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

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

2004-01-01

324

Serum Bone Alkaline Phosphatase Isoenzyme Levels in Normal Children and Children with Growth Hormone (GH) Deficiency: A Potential Marker for Bone Formation and Response to GH Therapy  

Microsoft Academic Search

Serum bone alkaline phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immuno- radiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal chil- dren (207 males and 156 females, age 0 -18 yr) and in 20 GH-deficient children (age 5-13 yr)

HITOSHI TOBIUME; SUSUMU KANZAKI; SHIGEKI HIDA; TAEKO ONO; TADASHI MORIWAKE; SHIGEKI YAMAUCHI; HIROYUKI TANAKA; YOSHIKI SEINO

325

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

PubMed Central

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

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

2013-01-01

326

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

327

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.

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

2014-01-01

328

Adiponectin receptor 1 regulates bone formation and osteoblast differentiation by GSK-3?/?-Catenin signaling in mice.  

PubMed

Adiponectin and its receptors are expressed in bone marrow-derived osteoblasts. Previous studies in vivo and in vitro have produced controversial results. The purpose of this study was to use porcine adiponectin receptor 1 transgenic mice (pAdipoR1) as a model to evaluate the role of AdipoR1 on bone physiology at different ages. pAdipoR1 transgenic mice had higher bone mineral density than wild-type mice in both genders at 56weeks of age. The bone volume and trabecular number, measured by micro-computed tomography (?CT) was significantly greater in transgenic than in wild-type female mice at both 8 and 56weeks of age. ELISA analysis revealed that both serum osteocalcin and osteoprotegerin (OPG) were significantly increased in 8-week old pAdipoR1 transgenic mice of both genders. Furthermore, serum OPG was elevated at 32 and 56weeks of age in female and male pAdipoR1 transgenic mice. Serum TRAP5b concentration was reduced in 8 and 56weeks old male pAdipoR1 mice compared with wild-type male mice. Knock-down of AdipoR1 significantly decreased gene expression of osteocalcin, OPG, alkaline phosphatase and msh homeobox 2 and the mineralization in MC3T3-E1 cells and mesenchymal stem cells. In addition, pathscan analysis and real-time PCR analysis suggest AdipoR1 regulates osteoblast differentiation through GSK-3 ? and ?-Catenin signaling. Consequently, the lack of AdipoR1 impaired osteoblast differentiation and bone formation. We conclude that AdipoR1 is a critical factor for the osteoblast differentiation and bone homeostasis. PMID:24713193

Lin, Yuan Yu; Chen, Ching Yi; Chuang, Tai Yuan; Lin, Yun; Liu, Hui Yu; Mersmann, Harry John; Wu, Shinn Chih; Ding, Shih Torng

2014-07-01

329

E3 ubiquitin ligase-mediated regulation of bone formation and tumorigenesis  

PubMed Central

The ubiquitination–proteasome and degradation system is an essential process that regulates protein homeostasis. This system is involved in the regulation of cell proliferation, differentiation and survival, and dysregulations in this system lead to pathologies including cancers. The ubiquitination system is an enzymatic cascade that mediates the marking of target proteins by an ubiquitin label and thereby directs their degradation through the proteasome pathway. The ubiquitination of proteins occurs through a three-step process involving ubiquitin activation by the E1 enzyme, allowing for the transfer to a ubiquitin-conjugated enzyme E2 and to the targeted protein via ubiquitin-protein ligases (E3), the most abundant group of enzymes involved in ubiquitination. Significant advances have been made in our understanding of the role of E3 ubiquitin ligases in the control of bone turnover and tumorigenesis. These ligases are implicated in the regulation of bone cells through the degradation of receptor tyrosine kinases, signaling molecules and transcription factors. Initial studies showed that the E3 ubiquitin ligase c-Cbl, a multi-domain scaffold protein, regulates bone resorption by interacting with several molecules in osteoclasts. Further studies showed that c-Cbl controls the ubiquitination of signaling molecules in osteoblasts and in turn regulates osteoblast proliferation, differentiation and survival. Recent data indicate that c-Cbl expression is decreased in primary bone tumors, resulting in excessive receptor tyrosine kinase signaling. Consistently, c-Cbl ectopic expression reduces bone tumorigenesis by promoting tyrosine kinase receptor degradation. Here, we review the mechanisms of action of E3 ubiquitin ligases in the regulation of normal and pathologic bone formation, and we discuss how targeting the interactions of c-Cbl with some substrates may be a potential therapeutic strategy to promote osteogenesis and to reduce tumorigenesis.

Severe, N; Dieudonne, F-X; Marie, P J

2013-01-01

330

Core formation, wet early mantle, and H2O degassing on early Mars  

NASA Technical Reports Server (NTRS)

Geophysical and geochemical observations strongly suggest a 'hot origin of Mars,' i.e., the early formation of both the core and the crust-mantle system either during or just after planetary accretion. To consider the behavior of H2O in the planetary interior it is specifically important to determine by what mechanism the planet is heated enough to cause melting. For Mars, the main heat source is probably accretional heating. Because Mars is small, the accretion energy needs to be effectively retained in its interior. Therefore, the three candidates of heat retention mechanism are discussed first: (1) the blanketing effect of the primordial H2-He atmosphere; (2) the blanketing effect of the impact-induced H2O-CO2 atmosphere; and (3) the higher deposition efficiency of impact energy due to larger impacts. It was concluded that (3) the is the most plausible mechanism for Mars. Then, its possible consequence on how wet the early martian mantle was is discussed.

Kuramoto, K.; Matsui, T.

1993-01-01

331

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

PubMed

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

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

2014-01-01

332

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.

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

333

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

PubMed

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

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

2013-06-01

334

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

PubMed Central

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

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

2013-01-01

335

Formation and processing of organics in the early solar system.  

PubMed

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

Kerridge, J F

1999-01-01

336

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.

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

2008-01-01

337

Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production  

PubMed Central

The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2–deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2–overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1?2 (col1?2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os’s) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans.

Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Schinke, Thorsten; Amling, Michael

2010-01-01

338

Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production.  

PubMed

The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2-deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2-overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1?2 (col1?2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os's) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans. PMID:20837772

Bozec, Aline; Bakiri, Latifa; Jimenez, Maria; Schinke, Thorsten; Amling, Michael; Wagner, Erwin F

2010-09-20

339

Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells  

Microsoft Academic Search

Supraphysiological concentrations of exogenous growth factors are typically required to obtain bone regeneration, and it is unclear why lower levels are not effective. We hypothesized that delivery of bone progenitor cells along with appropriate combinations of growth factors and scaffold characteristics would allow physiological doses of proteins to be used for therapeutic bone regeneration. We tested this hypothesis by measuring

Craig A. Simmons; Eben Alsberg; Susan Hsiong; Woo J. Kim; David J. Mooneya

2004-01-01

340

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

PubMed Central

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 analyzed 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 10-8M and ascorbic acid phosphate (AscP) at 10-4M. Our data demonstrate that for 22 out of 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 of 14 donors, BMSC strains cultured with and without Dex/AscP formed hematopoietic 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-Fibroblast. 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.

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

2011-01-01

341

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

342

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.

343

Star Formation in Early-type galaxies (Longhetti+ 1998)  

NASA Astrophysics Data System (ADS)

The paper is the first of a series (Longhetti et al., 1998A&AS..130..267L, 1998b (Paper III) in press) dedicated to the study of the star formation history in early-type galaxies which show fine structures and/or interaction signatures. It presents nuclear line-strength indices for a sample composed of 21 shell galaxies, from the Malin & Carter (1983ApJ...274..534M) southern survey, and 30 members of isolated interacting pairs, from the Reduzzi & Rampazzo (1995ApL....30....1R) catalogue, located in low density environments. The spectral range covers 3700Å4200Å) indices defined by the Lick Group. Measures have been transformed into the Lick-IDS ``standard'' system. The procedure has been tested on a set of 5 elliptical galaxies selected from the Gonzalez (1993, Ph.D. thesis) sample. We derive also three blue (?<4200) indices, namely {DELTA}(4000Å) defined by Hamilton (1985ApJ...297..371H), H+K(CaII) and Hdelta/FeI defined by Rose (1984AJ.....89.1238R, 1985AJ.....90.1927R). Blue indices are correlated to the age of the last starburst occurred in a galaxy (Leonardi & Rose, 1996AJ....111..182L). The indices determination, the estimate of the measurement errors and the correction for the galaxies velocity dispersions are discussed in detail. In the Appendix A we present the indices for a set of hot stars (T>10000K) which may be used for extending, toward high temperatures, Worthey (1992, Ph.D. Thesis) fitting functions. (12 data files).

Longhetti, M.; Rampazzo, R.; Bressan, A.; Chiosi, C.

1998-03-01

344

?-Catenin and BMP-2 Synergize to Promote Osteoblast Differentiation and New Bone Formation  

PubMed Central

Mutations of critical components of the Wnt pathway profoundly affect skeletal development and maintenance, probably via modulation of ?-catenin signaling. We tested the hypothesis that ?-catenin is involved in mesenchymal lineage allocation to osteogenic cells using a ?-catenin mutant with constitutive transcriptional activity (?N151). Although this stable ?-catenin had no effects by itself on osteogenic differentiation of multipotent embryonic cell lines, it synergized with bone morphogenetic protein-2 (BMP-2) resulting in dramatic stimulation of alkaline phosphatase activity, osteocalcin gene expression, and matrix mineralization. Likewise, ?N151 and BMP-2 synergistically stimulated new bone formation after subperiosteal injection in mouse calvaria in vivo. Conversely, ?N151 prevented adipogenic differentiation from pre-adipocytic or uncommitted mesenchymal cells in vitro. Intriguingly, the synergism with BMP-2 on gene transcription occurred without altering expression of Cbfa1/Runx2, suggesting actions independent or downstream of this osteoblast-specific transcription factor. Thus, ?-catenin directs osteogenic lineage allocation by enhancing mesenchymal cell responsiveness to osteogenic factors, such as BMP-2, in part via Tcf/Lef dependent mechanisms. In vivo, this synergism leads to increased new bone formation.

Mbalaviele, Gabriel; Sheikh, Sharmin; Stains, Joseph P.; Salazar, Valerie S.; Cheng, Su-Li; Chen, Di; Civitelli, Roberto

2009-01-01

345

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.

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

2013-01-01

346

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

PubMed Central

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

2013-01-01

347

Early Alteration in Bone Metabolism in Epileptic Children Receiving Carbamazepine Monotherapy Owing to the Induction of Hepatic Drug-Metabolizing Enzymes  

Microsoft Academic Search

The purpose of this study was to investigate, by a prospective, self-controlled method, whether early treatment with carbamazepine monotherapy can alter bone metabolism in ambulatory epileptic children with adequate sun exposure, based on the determination of total serum alkaline phosphatase and its bone isoenzyme activities. Serum total alkaline phosphatase and its bone, liver, and intestinal isoenzyme activities were evaluated in

Konstantinos A. Voudris; Achilleas Attilakos; Eustathia Katsarou; Anastasia Garoufi; Stamatia Dimou; Angeliki Skardoutsou; Sotiria Mastroyianni

2005-01-01

348

Role of flow cytometry of peripheral blood and bone marrow aspirates in early myeloma.  

PubMed

Flow cytometric immunophenotyping (FCM) of multiple myeloma (MM) is commonly accepted in academic centers as providing clinically significant information and is becoming increasingly utilized in the private setting. FCM has established clinical relevance in the following: (1) differential diagnosis of MM from other plasma cell dyscrasias; (2) differentiating MM from lymphoplasmacytic lymphoma (LPL) and other non-Hodgkin lymphomas; (3) diagnosis of unusual cases of myeloma (eg, to confirm the diagnosis of rare cases of IgM MM); (4) determining the risk of progression of monoclonal gammopathy of uncertain significance (MGUS) and smoldering MM; (5) prognostication in MM; and (6) minimal residual disease detection (MRD) post therapy. FCM may have an emerging role in the enumeration of abnormal plasma cells in diagnosis of MM, but further studies are needed. We review the clinical value of FCM in evaluation of peripheral blood and bone marrow in early myeloma. PMID:21232656

Yuan, Constance M; Stetler-Stevenson, Maryalice

2011-01-01

349

Early and late bone-marrow changes after irradiation: MR evaluation  

SciTech Connect

Knowledge of the chronologic evolution of bone-marrow changes during and after radiation therapy is essential in differentiating normal postradiation changes from other marrow abnormalities. The appearance of the lumbar vertebral bone marrow was studied on 55 serial spin-echo and short-T1 inversion-recovery (STIR) MR images obtained in 14 patients receiving radiation therapy for Hodgkin disease, seminoma, or prostate carcinoma. Images were obtained before, at weekly intervals during, and at various monthly intervals up to 14 months after a 3- to 6-week course of fractionated paravertebral lymph-node irradiation of 1500-5000 rad (15-50 Gy). During the first 2 weeks of therapy, there was no definite change in the appearance of the marrow on spin-echo images; however, there was an increase in signal intensity on the STIR images, apparently reflecting early marrow edema and necrosis. Between weeks 3 and 6, the marrow showed an increasingly heterogenous signal and prominence of the signal from central marrow fat, shown best on T1-weighted images. Late marrow patterns (6 weeks to 14 months after therapy) varied and consisted of either homogenous fatty replacement or a band pattern of peripheral intermediate signal intensity, possibly representing hematopoietic marrow surrounding the central marrow fat. No focal marrow lesions or soft-tissue edema were identified during the course of radiation therapy; their presence should raise the possibility of the presence of a pathologic process other than radiation change. These data suggest that MR can detect radiation-induced marrow changes as early as 2 weeks after starting therapy, and that there are at least two distinct types of late marrow MR patterns.

Stevens, S.K.; Moore, S.G.; Kaplan, I.D. (Stanford Univ. Medical Center, CA (USA))

1990-04-01

350

Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity  

PubMed Central

Background: Perspectives of immunotherapy to cancer mediated by bone marrow transplantation (BMT) in conjunction with dendritic cell (DC)-mediated immune sensitisation have yielded modest success so far. In this study, we assessed the impact of DC on graft vs tumour (GvT) reactions triggered by allogeneic BMT. Methods: H2Ka mice implanted with congenic subcutaneous Neuro-2a neuroblastoma (NB, H2Ka) tumours were irradiated and grafted with allogeneic H2Kb bone marrow cells (BMC) followed by immunisation with tumour-inexperienced or tumour-pulsed DC. Results: Immunisation with tumour-pulsed donor DC after allogeneic BMT suppressed tumour growth through induction of T cell-mediated NB cell lysis. Early post-transplant administration of DC was more effective than delayed immunisation, with similar efficacy of DC inoculated into the tumour and intravenously. In addition, tumour inexperienced DC were equally effective as tumour-pulsed DC in suppression of tumour growth. Immunisation of DC did not impact quantitative immune reconstitution, however, it enhanced T-cell maturation as evident from interferon-? (IFN-?) secretion, proliferation in response to mitogenic stimulation and tumour cell lysis in vitro. Dendritic cells potentiate GvT reactivity both through activation of T cells and specific sensitisation against tumour antigens. We found that during pulsing with tumour lysate DC also elaborate a factor that selectively inhibits lymphocyte proliferation, which is however abolished by humoral and DC-mediated lymphocyte activation. Conclusion: These data reveal complex involvement of antigen-presenting cells in GvT reactions, suggesting that the limited success in clinical application is not a result of limited efficacy but suboptimal implementation. Although DC can amplify soluble signals from NB lysates that inhibit lymphocyte proliferation, early administration of DC is a dominant factor in suppression of tumour growth.

Gigi, V; Stein, J; Askenasy, N; Yaniv, I; Ash, S

2013-01-01

351

Bone tissue formation under ideal conditions in a scaffold generated by a reaction-diffusion system.  

PubMed

The design of porous scaffolds for tissue engineering requires methods to generate geometries in order to control the stiffness and the permeability of the implant among others characteristics. This article studied the potential of the reaction-diffusion systems to design porous scaffolds for bone regeneration. We simulate the degradation of the scaffold material and the formation of new bone tissue over canal-like, spherical and ellipsoid structures obtained by this approach. The simulations show that the degradation and growth rates are affected by the form of porous structures. The results have indicated that the proposed method has potential as a tool to generate scaffolds with internal porosities and is comparable with other methodologies to obtain this type of structures. PMID:24015480

Velasco, A Marco; Garzón-Alvarado, Diego A

2013-06-01

352

Ectopic bone formation after medial femoral condyle graft to scaphoid nonunion.  

PubMed

Free vascularized bone graft from the medial femoral condyle has been described as a superior method for treatment of recalcitrant scaphoid nonunion with proximal pole avascularity and humpback deformity. Few complications and high union rates have been reported. In a series of three patients we describe an undesired volar ossification as a potential complication of the method. The risk of developing the ectopic bone formation can be minimized if the surgeon is aware of the strong osteogenic capacity of the periosteum. Meticulous dissection of the vascular bundle to the graft is mandatory to avoid the complication. Caution is warranted so as not to leave a periosteal sleeve under the vessels at the margin of the graft. PMID:24533246

Vedung, Torbjörn; Vinnars, Bertil

2014-02-01

353

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

PubMed Central

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

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

2010-01-01

354

[Effect of osteogenically and adipogenically differentiated bone mesenchymal stem cells from mouse on osteoclast formation].  

PubMed

This study was purposed to investigate the regulatory effects of differentiating mesenchymal stem cells (MSC) on osteoclast formation. The MSC from mouse compact bones were cultured and induced into osteoblasts and adipocytes for one week. To test their regulatory effect on osteoclastogenesis, osteogenically differentiated and adipogenically differentiated MSC were co-cultured with CD11b(+) monocytes and osteoclasts were identified with in situ tartrate-resistant acid phosphatase (TRAP) staining. The results showed that differentiated MSC supported osteoclastogenesis but the osteoclast supporting capacity of osteogenically differentiated MSC decreased as compared with undifferentiated MSC. More interestingly, the adipogenically differentiated MSC significantly promoted osteoclasts formation when co-cultured with monocytes. It is concluded that the regulatory effect of MSC on osteoclast formation has changed while they have differentiated into different types of cells. The findings indicate that MSC may exert alternative effect on osteoclastogenesis by differentiation to descendant cells. PMID:23114145

Zhu, Heng; Liu, Yuan-Lin; Chen, Ji-De; Li, Hong; Liu, Yu-Xiao; Xu, Fen-Fen; Jiang, Xiao-Xia; Zhang, Yi; Mao, Ning

2012-10-01

355

Osteoclasts on bone and dentin in vitro: mechanism of trail formation and comparison of resorption behavior.  

PubMed

The main function of osteoclasts in vivo is the resorption of bone matrix, leaving behind typical resorption traces consisting of pits and trails. The mechanism of pit formation is well described, but less is known about trail formation. Pit-forming osteoclasts possess round actin rings. In this study we show that trail-forming osteoclasts have crescent-shaped actin rings and provide a model that describes the detailed mechanism. To generate a trail, the actin ring of the resorption organelle attaches with one side outside the existing trail margin. The other side of the ring attaches to the wall inside the trail, thus sealing that narrow part to be resorbed next (3–21 lm). This 3D configuration allows vertical resorption layer-by-layer from the surface to a depth in combination with horizontal cell movement. Thus, trails are not just traces of a horizontal translation of osteoclasts during resorption. Additionally, we compared osteoclastic resorption on bone and dentin since the latter is the most frequently used in vitro model and data are extrapolated to bone. Histomorphometric analyses revealed a material-dependent effect reflected by an 11-fold higher resorption area and a sevenfold higher number of pits per square centimeter on dentin compared to bone. An important material-independent aspect was reflected by comparable mean pit area (?m²) and podosome patterns. Hence, dentin promotes the generation of resorbing osteoclasts, but once resorption has started, it proceeds independently of material properties. Thus, dentin is a suitable model substrate for data acquisition as long as osteoclast generation is not part of the analyses. PMID:24022329

Rumpler, M; Würger, T; Roschger, P; Zwettler, E; Sturmlechner, I; Altmann, P; Fratzl, P; Rogers, M J; Klaushofer, K

2013-12-01

356

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

357

Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation.  

PubMed

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

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

2014-02-01

358

Human bone-derived cells support formation of human osteoclasts from arthroplasty-derived cells in vitro.  

PubMed

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH)2 vitamin D3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human