Home About us Contact
|
Home About us Contact | ||
|
|
||
Increased Bone Formation (increased + bone_formation)
Selected AbstractsTargeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2008Xiaodong Li Abstract Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone. Materials and Methods: Gene targeting was used to inactivate SOST and generate a line of SOST KO mice. Radiography, densitometry, ,CT, histomorphometry, and mechanical testing were used to characterize the impact of sclerostin deficiency on bone in male and female mice. Comparisons were made between same sex KO and wildtype (WT) mice. Results: The results for male and female SOST KO mice were similar, with differences only in the magnitude of some effects. SOST KO mice had increased radiodensity throughout the skeleton, with general skeletal morphology being normal in appearance. DXA analysis of lumbar vertebrae and whole leg showed that there was a significant increase in BMD (>50%) at both sites. ,CT analysis of femur showed that bone volume was significantly increased in both the trabecular and cortical compartments. Histomorphometry of trabecular bone revealed a significant increase in osteoblast surface and no significant change in osteoclast surface in SOST KO mice. The bone formation rate in SOST KO mice was significantly increased for trabecular bone (>9-fold) at the distal femur, as well as for the endocortical and periosteal surfaces of the femur midshaft. Mechanical testing of lumbar vertebrae and femur showed that bone strength was significantly increased at both sites in SOST KO mice. Conclusions:SOST KO mice have a high bone mass phenotype characterized by marked increases in BMD, bone volume, bone formation, and bone strength. These results show that sclerostin is a key negative regulator of a powerful, evolutionarily conserved bone formation pathway that acts on both trabecular and cortical bone. [source] Increased Bone Formation in Mice Lacking Plasminogen Activators,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2003E Daci Abstract Plasminogen activators tPA and uPA are involved in tissue remodeling, but their role in bone growth is undefined. Mice lacking tPA and uPA show increased bone formation and bone mass. The noncollagenous components of bone matrix are also increased, probably from defective degradation. This study underlines the importance of controlled bone matrix remodeling for normal endochondral ossification. Introduction: Proteolytic pathways are suggested to play a role in endochondral ossification. To elucidate the involvement of the plasminogen activators tPA and uPA in this process, we characterized the long bone phenotype in mice deficient in both tPA and uPA (tPA,/,:uPA,/,). Materials and Methods: Bones of 2- to 7-day-old tPA,/,:uPA,/, and wild-type (WT) mice were studied using bone histomorphometry, electron microscopy analysis, and biochemical assessment of bone matrix components. Cell-mediated degradation of metabolically labeled bone matrix, osteoblast proliferation, and osteoblast differentiation, both at the gene and protein level, were studied in vitro using cells derived from both genotypes. Results: Deficiency of the plasminogen activators led to elongation of the bones and to increased bone mass (25% more trabecular bone in the proximal tibial metaphysis), without altering the morphology of the growth plate. In addition, the composition of bone matrix was modified in plasminogen activator deficient mice, because an increased amount of proteoglycans (2×), osteocalcin (+45%), and fibronectin (+36%) was detected. Matrix degradation assays showed that plasminogen activators, by generating plasmin, participate in osteoblast-mediated degradation of the noncollagenous components of bone matrix. In addition, proliferation of primary osteoblasts derived from plasminogen activator-deficient mice was increased by 35%. Finally, osteoblast differentiation and formation of a mineralized bone matrix were enhanced in osteoblast cultures derived from tPA,/,:uPA,/, mice. Conclusions: The data presented indicate the importance of the plasminogen system in degradation of the noncollagenous components of bone matrix and suggest that the accumulation of these proteins in bone matrix,as occurs during plasminogen activator deficiency,may in turn stimulate osteoblast function, resulting in increased bone formation. [source] In vivo bioluminescence imaging study to monitor ectopic bone formation by luciferase gene marked mesenchymal stem cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2008Cristina Olivo Abstract Mesenchymal stem cells (MSCs) represent a powerful tool for applications in regenerative medicine. In this study, we used in vivo bioluminescence imaging to noninvasively investigate the fate and the contribution to bone formation of adult MSCs in tissue engineered constructs. Goat MSCs expressing GFP-luciferase were seeded on ceramic scaffolds and implanted subcutaneously in immune-deficient mice. The constructs were monitored weekly with bioluminescence imaging and were retrieved after 7 weeks to quantify bone formation by histomorphometry. With increasing amounts of seeded MSCs (from 0 to 1,×,106 MSC/scaffold), a cell-dose related increase in bioluminescence was observed at all time points, correlating with increased bone formation at 7 weeks. To investigate the relevance of MSC proliferation to bone deposition, cell-seeded scaffolds were irradiated. The irradiated cells were functional with respect to oxygen consumption but no increase in bioluminescence was observed in vivo, and only minimal bone was produced. Proliferating MSCs are likely required for initiation of bone formation in tissue engineered constructs in vivo. Bioluminescence is a useful tool to monitor cellular responses and predict bone formation in vivo. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:901,909, 2008 [source] Biodegradable polylactide membranes for bone defect coverage: biocompatibility testing, radiological and histological evaluation in a sheep modelCLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2006Gerhard Schmidmaier Abstract: Large bony defects often show a delayed healing and have an increasing risk of infection. Several materials are used for the coverage of large defects. These materials must be biocompatible, easy to use, and must have an appropriate stability to present a mechanical hindrance. Aim of this study was to investigate two different biodegradable membranes for defect coverage in a sheep model. Round cranial defects (1.5 cm diameter) were created in sheep. Six different treatments were investigated: defects without membrane, defects covered with a poly(d,l -lactide) or with a 70/30 poly(l/d,l -lactide) membrane and all defects with or without spongiosa filling. The sheep were sacrificed 12 or 24 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on CT radiographs. Histomorphometry and host-tissue response were evaluated by light microscopy. The biocompatibility was investigated by analyzing the amount of osteoclasts and foreign body cells. Both membranes served as a mechanical hindrance to prevent the prolapse of soft tissue into the defect. The biocompatibility test revealed no differences in the amount and distribution of osteoclasts at the two investigated time points and between the investigated groups. No negative effect on the tissue regeneration was detectable between the investigated groups related to the type of membrane, but a foreign body reaction around the two membrane types was observed. In the membrane-covered defects, the spongiosa showed a progressing remodeling to the native bony structure of the cranium. The groups without spongiosa partly revealed new bone formation, without complete bridging in any group or at any time point. Comparing the 12 and 24 weeks groups, an increased bone formation was detectable at the later time point. In conclusion, the results of the present in vivo study reveal a good biocompatibility and prevention of soft tissue prolapse of the two used membranes without differences between the membranes. An enhanced remodeling of the spongiosa into native bony structures under the membranes was detectable, but no osteopromoting effect was observed due to the membranes. [source] | ||||||||||