2014 Fiscal Year Final Research Report
A novel regulation of farnesyl diphosphate synthase (FDPS) on the activity of Cl- extrusion in osteoclasts
| Project/Area Number |
24592823
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Fujio 福岡歯科大学, 口腔歯学部, 講師 (60153938)
OKABE Koji 福岡歯科大学, 口腔歯学部, 教授 (80224026)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 骨代謝 / 破骨細胞 / 酸分泌輸送体 / ビスホスホネート製剤 |
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| Outline of Final Research Achievements |
Farnesyl diphosphate synthase (FDPS) have well known to be inhibited by nitrogen-containing bisphosphonates, leading to suppression of bone resorption in mature osteoclasts. However, little is known whether FDPS regulate directly the extrusion activity of ClC-7 Cl- transporters (ClC7) in mature osteoclasts. FDPS was associated and colocalized with ClC7 in mouse osteoclasts and HEK cells coexpressing FDPS and ClC7. Extracellular acidification induced outwardly rectifying Cl- currents (acid-induced Cl- currents) and decreased intracellular Cl- concentration ([Cl-]i) associated with ClC7 in osteoclasts. Zoledronic acid, FDPS inhibitors suppressed the acid-induced Cl- currents and [Cl-]i reduction. In transgenic mice overexpressing with FDPS (FDPS Tg-mice), bone mineral density significantly decreased with elevation of the bone resorption parameters. The results suggest that FDPS may contribute to regulate the bone resorption activity, especially the ClC7 activity in mature osteoclasts.
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| Free Research Field |
歯学・機能系基礎歯学
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