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Endosteal Bone Formation (endosteal + bone_formation)
Selected AbstractsRestoration of Bone Mass and Strength in Glucocorticoid-Treated Mice by Systemic Transplantation of CXCR4 and Cbfa-1 Co-Expressing Mesenchymal Stem Cells,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2009Chun-Yang Lien Abstract Transplantation of gene-modified mesenchymal stem cells (MSCs) in animals for bone regeneration therapy has been evaluated extensively in recent years. However, increased endosteal bone formation by intravenous injection of MSCs ectopically expressing a foreign gene has not yet been shown. Aside from the clearance by lung and other tissues, the surface compositions of MSCs may not favor their bone marrow (BM) migration and engraftment. To overcome these hurdles, a gene encoding the chemokine receptor largely responsible for stromal-derived factor-1 (SDF-1)-mediated BM homing and engraftment of hematopoietic stem cells (HSCs), CXCR4, was transduced into mouse C3H10T1/2 cells by adenovirus infection. A dose-dependent increase of CXCR4 surface expression with a parallel enhanced chemotaxis toward SDF-1 in these cells after virus infection was clearly observed. Higher BM retention and homing of CXCR4-expressing MSCs were also found after they were transplanted by intramedullary and tail vein injections, respectively, into immunocompetent C3H/HeN mice. Interestingly, a full recovery of bone mass and a partial restoration of bone formation in glucocorticoid-induced osteoporotic mice were observed 4 wk after a single intravenous infusion of one million CXCR4-expressing C3H10T1/2 cells. In the meantime, complete recovery of bone stiffness and strength in these animals was consistently detected only after a systemic transplantation of CXCR4 and Cbfa-1 co-transduced MSCs. To our knowledge, this is the first report to show unequivocally the feasibility of ameliorating glucocorticoid-induced osteoporosis by systemic transplantation of genetically manipulated MSCs. [source] IGF-I Receptor Is Required for the Anabolic Actions of Parathyroid Hormone on Bone,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2007Yongmei Wang Abstract We showed that the IGF-IR,null mutation in mature osteoblasts leads to less bone and decreased periosteal bone formation and impaired the stimulatory effects of PTH on osteoprogenitor cell proliferation and differentiation. Introduction: This study was carried out to examine the role of IGF-I signaling in mediating the actions of PTH on bone. Materials and Methods: Three-month-old mice with an osteoblast-specific IGF-I receptor null mutation (IGF-IR OBKO) and their normal littermates were treated with vehicle or PTH (80 ,g/kg body weight/d for 2 wk). Structural measurements of the proximal and midshaft of the tibia were made by ,CT. Trabecular and cortical bone formation was measured by bone histomorphometry. Bone marrow stromal cells (BMSCs) were obtained to assess the effects of PTH on osteoprogenitor number and differentiation. Results: The fat-free weight of bone normalized to body weight (FFW/BW), bone volume (BV/TV), and cortical thickness (C.Th) in both proximal tibia and shaft were all less in the IGF-IR OBKO mice compared with controls. PTH decreased FFW/BW of the proximal tibia more substantially in controls than in IGF-IR OBKO mice. The increase in C.Th after PTH in the proximal tibia was comparable in both control and IGF-IR OBKO mice. Although trabecular and periosteal bone formation was markedly lower in the IGF-IR OBKO mice than in the control mice, endosteal bone formation was comparable in control and IGF-IR OBKO mice. PTH stimulated endosteal bone formation only in the control animals. Compared with BMSCs from control mice, BMSCs from IGF-IR OBKO mice showed equal alkaline phosphatase (ALP)+ colonies on day 14, but fewer mineralized nodules on day 28. Administration of PTH increased the number of ALP+ colonies and mineralized nodules on days 14 and 28 in BMSCs from control mice, but not in BMSCs from IGF-IR OBKO mice. Conclusions: Our results indicate that the IGF-IR null mutation in mature osteoblasts leads to less bone and decreased bone formation, in part because of the requirement for the IGF-IR in mature osteoblasts to enable PTH to stimulate osteoprogenitor cell proliferation and differentiation. [source] The effect of aging on distraction osteogenesis in the ratJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2001J. Aronson The effect of age on bone formation in the limb lengthening model of distraction osteogenesis (DO) was investigated in two studies using Sprague,Dawley (SD) rats from two colonies at various ages (CAMM: 9 vs 24 months, Harlan: 4 vs 24 months). External fixators were placed on the right tibiae of 30 male SD rats (20 CAMM, 10 Harlan) and mid-diaphyseal osteotomies were performed. Distraction was performed at 0.2 mm bid for 20 days (CAMM) or 14 days (Harlan). The experimental (DO) and control (contra-lateral) tibiae were removed for high-resolution radiography and decalcified histology. Videomicroscopy was used to quantitate radiodensity, histology (matrix type) and relative areas of cell proliferation, which was identified by proliferating cell nuclear antigen (PCNA) immunochemistry. Both studies demonstrated an age-related decrease in the percent mineralized bone (radiodensity) in the distraction gap (CAMM 9 vs 24 months: 68% vs 51%, P < 0.003; Harlan 4 vs 24 months: 95% vs 36%, P < 0.001) and no significant colony or distraction time-specific difference was seen between the two colonies of 24-month-old rats. Histology was performed on the Harlan rats. The DO gaps in the 24-month-old rats demonstrated less endosteal new bone compared to the 4-month-old rats (P < 0.01), but equivalent periosteal new bone. In 4-month-old rats, PCNA-immunostained cells were organized along the primary matrix front (where the first deposition of osteoid occurs) extending across both periosteal and endosteal surfaces. In 24-month-old rats, PCNA + cells were organized in zones along the periosteal new bone fronts only and irregularly scattered throughout the endosteal gap within a fibrovascular non-ossifying matrix. These results indicate that 24-month-old rats have a relative deficit in endosteal bone formation which may not be related to cell proliferation but rather to cell organization. This model reflects the clinical situation where radiographic findings in older patients demonstrate significant delays in mineralization during DO. We believe this model of DO in aged rats presents unique in vivo opportunities to test hypotheses concerning (1) the effects of aging on bone repair, (2) the effects of pharmacological agents on bone repair in a geriatric setting, and (3) to study the mechanisms underlying DO. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Local ex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in miceTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Xiao S. Zhang Abstract Background Bone loss in osteoporosis is caused by an imbalance between resorption and formation on endosteal surfaces of trabecular and cortical bone. We investigated the feasibility of increasing endosteal bone formation in mice by ex vivo gene therapy with bone marrow stromal cells (MSCs) transduced with a MLV-based retroviral vector to express human bone morphogenetic protein 4 (BMP4). Methods We assessed two approaches for administering transduced MSCs. ,-Galactosidase (,-Gal) transduced C57BL/6J mouse MSCs were injected intravenously via tail vein or directly injected into the femoral bone marrow cavity of non-marrow-ablated syngenic recipient mice and bone marrow cavity engraftment was assessed. BMP4- or ,-Gal-transduced cells were injected into the femoral bone marrow cavity and effects on bone were evaluated by X-ray, peripheral quantitative computed tomography (pQCT), and histology. Results After tail-vein injection less than 20% of recipient mice contained ,-Gal-positive donor cells in femur, humerus or vertebra marrow cavities combined, and in these mice only 0.02,0.29% of injected cells were present in the bone marrow. In contrast, direct intramedullary injection was always successful and an average of 2% of injected cells were present in the injected femur marrow cavity 24 hours after injection. Numbers of donor cells decreased over the next 14 days. Intramedullary injection of BMP4-transduced MSCs induced bone formation. Trabecular bone mineral density (BMD) determined by pQCT increased 20.5% at 14 days and total BMD increased 6.5% at 14 days and 10.4% at 56 days. Conclusions The present findings support the feasibility of using ex vivo MSC-based retroviral gene therapy to induce relatively sustained new bone formation, with normal histological appearance, at endosteal bone sites. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||