1999 Fiscal Year Final Research Report Summary
Regulation of Osteoclast function by H-ATPase Inhibitor
| Project/Area Number |
10671712
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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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| Project Period (FY) |
1998 – 1999
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| Keywords | Osteoclast / Ruffled border / HィイD1+ィエD1-ATPase inhibitor / Bafilomycin A1 / Bisphosphonate / Bone resorption / Bone remodelling / Electron microscopy |
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| Research Abstract |
Vacuolar-type HィイD1+ィエD1-ATPase in multinucleated osteoclastic cells is the most important enzyme for demineralization of apatite crystals in bone and teeth. We localized the expression of vacuolar-type HィイD1+ィエD1-ATPase in osteoclasts and odontoclasts during bone and root resorption. Most of these multinucleated osteo/odontoclasts exhibited well-developed ruffled borders and clear zones, and HィイD1+ィエD1-ATPase was localized along the limiting membranes of pale vacuoles and along the ruffled border membranes. We further clarified the effects of administering bafilomycin A1 on the bone resorbing activity of osteoclasts during experimental movement of rat molars. To generate orthodontic force, an elastic band was inserted between the upper first and second molars of rats for 7 days. After elastic band application, bafilomycin A1 solution was administered daily intraperitoneally, and the structural changes and the expression of HィイD1+ィエD1-ATPase in osteo/ odontoclasts were examined. In bafilomycin A1-administered rats, most osteo/ odontoclasts had lost their intact ruffled borders and associated cytoplasmic vacuoles and showed decreased expression of HィイD1+ィエD1-ATPase. These results suggest that bafilomycin A1 administration is an effective biological means to inhibit osteoclastic bone resorption and odontoclastic root resorption via a mechanism involving impairment of the structure and function of the ruffled borders in osteo/oodontoclasts.
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