Mitochondrial transcription factor A in oseocytes is involved in bone metabolism by regulating osteoclastic bone resorption

2015 Fiscal Year Final Research Report

• Project/Area Number: 25462393
• 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: Tokimura Fumiaki 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 (80242147)
• Co-Investigator(Kenkyū-buntansha): 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ミトコンドリア / 骨細胞 / 破骨細胞 / 骨吸収

Outline of Final Research Achievements

Mitochondrial transcription factor A (Tfam) is necessary for mtDNA maintenance in mammals and regulates mtDNA copy number by directly binding and coating mtDNA. In addition, Tfam is absolutely required for transcription initiation at mtDNA promoters.
To investigate the role of Tfam in bone metabolism, we generated osteocyte-specific Tfam conditional knockout (cKO) mice by mating Tfamflox/flox mice with Dmp1-Cre transgenic mice, in which the Cre recombinase gene was specifically expressed in osteocytes. Tfam cKO mice exhibited a remarkable decrease in bone volume. Histomorphometric analysis of Tfam 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 Tfamflox/flox littermates. Collectively, these findings suggest that the bone loss in Tfam cKO mice was caused by increased bone-resorbing activity, rather than by decreased bone formation.

Free Research Field

整形外科学