| Summary: | 碩士 === 國防醫學院 === 生物及解剖學研究所 === 96 === Aging is associated with bone loss resulting from decreased connection of bone trabeculae, leading to decrease bone resistance and increase risk of fracture(osteoporosis). A better knowledge and identification of key signals for lineage-specific differentiation of bone marrow mesenchymal stem cells (MSCs) will help us to develop therapeutic strategies for age-related osteopenia by promoting the
differentiation of these cells towards the osteoblast lineage .Transforming growth factor-β (TGF-β) is secreted and stored in bone matrix, which is decreased with age. In addition, TGF-β has been shown to stimulate osteoblastic differentiation but inhibit PPAR-γ expression and differentiation of late stage adipocyte as compound to bone morphogenic protein (BMP-2). The above information lead us to assume that TGF-β may play a role in regulating the marrow stem cells toward osteoblast differentiation during aging. The purposes of this study were to investigate 1) changes in osteogenic differentiation of marrow MSC-enriched cells using 4-and 20-month male ICR mice and 2) possible effects and mechanism of TGF-β2 (0.1,1,5ng/ml) and TGF-β2(1ng/ml)+ BMP (bone morphogenic protein)-2 (10ng/ml) on modulating MSC toward osteoblast differentiation, using density gradient separation method, osteoblast differentiation assay (Cbfa-1, osteocalcin expression), phase contrast microscopy, RT-PCR and Western blotting. Different dose of TGF-β2 significantly enhance osteogenic differentiation of MSC by increase in Cbfa1, osteocalcin and bone colony formation. In addition , TGF-β2 (5ng/ml) showed the best osteogenic potential as compared to the other groups.
The results of this study indicated that TGF-β2 may act as osteogenic modulator of marrow MSC-enriched cells in both adult and old mice.
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