Research on the Molecular Mechanism of Osteoporosis

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This research established molecular mechanisms playing a role in bone metabolism with special emphasis on the molecular detail of osteoblastic and osteoclastic differentiation as well as regulation of its function. We identified that TGFbeta-type III receptor expression is regulated by calcitropic hormones and found that osteoblastic cells express helix-loop-helix (HLH) type transcription (TF) factors whose expression is under the control of vitamin D and bone morphogenetic protein (BMP). We also found that a osteoblast-specific protein, osteocalcin, is expressed under the control of HLH-TF via the E-box region in the promoter region. Furthermore, we found that other types of HLF-TF such as ADD1 and HES1 are also expressed in osteoblasts and are regulated by retinoic acid and vitamin D respectively. This research focused especially on skeletal cell related HLH-TF,scleraxis, which is expressed in sclerotome. We found that scleraxis is expressed in osteoblasts and is regulated by TGFbeta. Furthermore, TGFbeta regulated as scleraxis in osteoblasts. Research on osteoclastogenesis was also established in this project by establishing clonal cell line which efficiently supports osteoclast formation. These accomplishments on molecular and cellular detail in bone metabolism brought new sinsignts into osteoporosis pathogenesis and contribute to establish treatment for osteoporosis.