Mechanosensor protein p130Cas in osteocytes is important for bone metabolism

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592290
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: MIYAZAKI TSUYOSHI 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50376480)
• Co-Investigator(Kenkyū-buntansha): MIYAMOTO Yoshinaro 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (10345217)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: メカニカルストレス / 骨細胞

Outline of Final Research Achievements

The adaptor molecule p130Cas, which is phosphorylated at focal adhesions upon extracellular matrix engagement, is involved in various cellular processes including migration, survival, transformation, and invasion.
To investigate the role of Cas in bone metabolism, we generated osteocyte-specific Cas conditional knockout (cKO) mice by mating Casflox/flox mice with Dmp1-Cre transgenic mice, in which the Cre recombinase gene was specifically expressed in osteocytes. The resulting Cas cKO mice exhibited a remarkable decrease in bone volume. Histomorphometric analysis of Cas cKO mice revealed a significant increase in the eroded surface/bone surface ratio, osteoclast surface, and osteoclast number. However, the bone formation parameters were equivalent to those in normal Casflox/flox littermates. Collectively, these findings suggest that the bone loss in Cas cKO mice was caused by increased bone-resorbing activity, rather than by decreased bone formation.

Free Research Field

外科系臨床医学・整形外科学