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Investigation of the mechanism of osteoclastic bone resorption by c-Src

Research Project

Project/Area Number 25670870
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthodontics/Pediatric dentistry
Research InstitutionTohoku University

Principal Investigator

MATSUBARA Takuma  東北大学, 大学病院, 助教 (00423137)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords骨吸収 / 破骨細胞
Outline of Final Research Achievements

A tyrosine kinase c-Src is necessary for ruffled border formation, the important structure in osteoclastic bone resorption. The ruffled border is actin accumulated structure and needed for adhesion to bone matrix. The mechanism of actin organization in osteoclasts(OCLs) by c-Src is still unclear. c-Src deficient mice have phenotypes only in bone tissue, although c-Src is ubiquitously expressed. This suggests the importance of c-Src in osteoclasts and compensate by other Src family kinases (SFKs) in other tissues. Thus I compared the role of c-Src with other SFKs in OCLs. c-Src was not only highly expressed but also had unique role in OCLs. In addition, the unique role of c-Src originated from SH3 domain and kinase domain.
I also looked for the novel protein that worked as actin regulation protein downstream of c-Src and found a candidate, “PPP1r18”. PPP1r18 was localized in actin ring in OCLs and the unique actin dot structure, podsomes formed by activated c-Src in fibroblasts.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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