Elucidation of the role of Sirt6 in the chondrocyte metabolism

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592257
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ASOU Yoshinori 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (50345279)
• Co-Investigator(Kenkyū-buntansha): 辻 邦和 東京医科歯科大学, 大学院医歯(薬)学総合研究科, 准教授 (20323694)
• Co-Investigator(Renkei-kenkyūsha): 荻島 創一 東北大学, 東北メディカルメガバンク機構, 講師 (40447496)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: サーチュイン / 軟骨代謝 / 老化

Outline of Final Research Achievements

The aim of this study was to investigate the Sirt6 signal pathway in cartilage metabolism.Sirt6 was expressed in primary chondrocytes and the chondrocyte-like cell line ATDC5. At birth, the length of the tibia and femur was shorter in Sirt6-/-. In the growth plate (GP), PCNA expression was reduced in Sirt6-/- mice. The number of TUNEL positive cells was comparable between Sirt6-/- and littermates. Two weeks after birth, growth retardation was apparent in Sirt6-/-, with reduced proliferating zone and hypertrophic zone in the growth plate, delayed ossification of secondary ossification center and decreased primary spongiosa. mRNA and protein expression of Col2a1, Col10a1 and Ihh in the growth plate was reduced in Sirt6-/- primary chondrocytes. Functional analysis revealed Sirt6 positively regulates chondrocyte differentiation via the Atf4 -Ihh axis.

Free Research Field

分子生物学