1996 Fiscal Year Final Research Report Summary
Development of a new therapeutic approach for senile osteoporosis using bone matrix deoorin
| Project/Area Number |
06557055
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
内分泌・代謝学
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| Research Institution | University of Tokyo School |
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Principal Investigator |
MATSUMOTO Toshio University of Tokyo, 4th Dept of Internal Med, Lecturer, 医学部・附属病院(分), 講師 (20157374)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kazuhiro Mitsubishi Chemical, Applied Biology Res Lab, Researcher, 応用生物研究所, 研究員
TAKEUCHI Yasuhiro University of Tokyo, 4th Dept of Internal Med, Assistant Professor, 医学部・附属病院(分), 助手 (50202164)
FUKUMOTO Seiji University of Tokyo, 4th Dept of Internal Med, Assistant Professor, 医学部・附属病院(分), 助手 (30202287)
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| Project Period (FY) |
1994 – 1996
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| Keywords | decorin / osteoblast / bone matrix / bone formation / aging / senile osteoporosis / TGF-beta |
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| Research Abstract |
Bone matrix decorin binds transforming growth factor (TGF)-beta with high affinity, and the binding of TGF-beta with decorin increases its binding to TGF-beta receptors (Takeuchi et al. J Biol Chem 269 : 32634,1994). These results suggested that decorin may serve as a binding protein of TGF-beta in bone matrix, and may modilate the actions of TGF-beta during bone formation process. It has been postulated that a reduction in the actions of growth factors including TGF-beta plays an important role in the development of senile osteoporosis. The present studies are undertaken to clarify the role of decorin in the deposition of TGF-beta into bone matrix as well as the regulation of TGF-beta actions in bone. Furthermore, recombinant decorin was prepared in order to develop a new therapeutic approach to senile osteoporosis by a targeted application of recombinant decorin to bone.
Osteoblasts posess specific binding sites for decorin on the plasma membrane, and the binding of decorin to its binding sites causes an internalization and degradation of decorin. Binding of TGF-beta-bound decorin to its binding sites facilitates the binding of TGF-beta to TGF-beta receptors, which appears to be the mechanism whereby the binding of TGF-beta to decorin enhances its actions. The present studies also demonstrated that binding sites for decorin is upregulated by active vitamin D metabolites. Although age-related changes in the content of decroin in bovine bone matrix was examined, no obvious changes could be detected. Finally, recombinant human decorin was prepared by transfecting human decorine c DNA into CHO cells. However, enough materials could not be obtained to allow investigations into the in vivo effect of recombinant decorin in the prevention of age-related bone loss.
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