2004 Fiscal Year Final Research Report Summary
Establishment of Bone Metabolism Research through Regulation of Osteoclast Differentiation and Functions
| Project/Area Number |
15591947
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
SASAKI Takahisa Showa University, School of Dentistry, Professor, 歯学部, 教授 (50129839)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Naoyuki Matsumoto Dental University, Institute for Dental Science, Professor, 総合歯科医学研究所, 教授 (90119222)
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| Project Period (FY) |
2003 – 2004
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| Keywords | in vitro / in vivo / RANKL / OPG / H-ATPase / cathepsin K / osteoclast / osteoporosis |
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| Research Abstract |
We conducted in vitro and in vivo experiments to clarify the biological effects of receptor activator of NFkB ligand (RANKL) and osteoprotegerin (OPG). We also examined the effects of potent and specific inhibitors for H-ATPase and cathepsin K in osteoclasts. The main methods we conducted were (1) cultures of osteoclast precursors and mature osteoclasts, (2) quantitative morphometry of resorption lacunae formed on co-cultured dentine slices, (3) ultrastructural observations of osteoclasts, (4) immunohistochemistry of H-ATPase and cathepsin K in osteoclasts, (5) scanning electron microscopic observations of resorption lacunae and associated osteoclasts. In this project, we examined specific biological effects of these cytokines and inhibitors for differentiation of osteoclast precursors. We also examined specific biological effects of these cytokines and inhibitors for cell structure, survival time, resorptive functions of mature osteoclasts. In addition, we cultured osteoclast precursors on the slices of calcified bone, decalcified bone, or uncalcified cartilage and found that osteoclast differetiation and functions were different depend on these substrata. In our in vivo experiments, we conducted morphometric and immunocytochemical examinations to clarify the effects of bisphosphonate or OPG on osteoclast differentiation and functional structures to inhibit acute bone loss in estrogen-deficient osteoporosis animal models. All the results obtained suggest that regulation of osteoclast differentiation is effective biological tool to normalize bone metabolism in various metabolic bone diseases.
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