2013 Fiscal Year Final Research Report

Identification and characterization of osteoclast-derived coupling factor

Research Project

Project/Area Number	24790371
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Human pathology
Research Institution	National Center for Geriatrics and Gerontology
Principal Investigator	MATSUOKA Kazuhiko 独立行政法人国立長寿医療研究センター, 運動器疾患研究部, 流動研究員 (00581365)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	骨芽細胞 / 破骨細胞 / カップリング / 骨リモデリング / 細胞分解
Research Abstract	Bone remodeling is regulated by a coupling of resorption to subsequent formation, however, the "coupling factor" and underlying mechanism are not fully understood. I purified osteoblast-stimulating activity, as determined by ALP activity, from osteoclast CM through successive chromatography by monitoring the ALP activity, and identified complement component 3 (C3). The activity present in osteoclast CM was inhibited by a specific C3a receptor antagonist, SB290157. C3 gene expression in bone was increased in the high bone turnover states of ovariectomy (OVX) or a RANKL injection, and blocking the action of C3a with the daily administration of SB290157 resulted in the attenuation of bone formation elevated by OVX, and the exacerbation of bone loss. These results suggest that osteoclast-derived C3a functions in the relay from bone resorption to formation and may be a candidate for a coupling factor.

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