The rola of Sirt6 in bone and cartilage metabolism

2017 Fiscal Year Final Research Report

• Project/Area Number: 26293332
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OKAWA Atsushi 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30251507)
• Co-Investigator(Kenkyū-buntansha): 麻生 義則 東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (50345279)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: Sirt6 / senescence / 骨代謝 / 軟骨代謝

Outline of Final Research Achievements

Ageing is a pivotal risk factor for osteoporosis and osteoarthritis. The stress-response and chromatin-silencing factor Sir2, a yeast sirtuin, is a NAD+-dependent histone deacetylase and is involved in controlling ageing. Herein we sought to investigate the involvement of Sirt6 in the etiology of osteoporosis and osteoarthritis. Sirt6 haploinsufficiency in mice promoted the expression of inflammatory cytokines in the IPFP. Mesenchyme-specific Sirt6-deficient mice revealed both attenuated chondrocyte hypertrophy and proteoglycan synthesis, although chondrocyte senescence was enhanced as shown in the aged WT mice. Thus Sirt6 has key roles in the relationship among ageing, metabolic syndrome, and OA.

Free Research Field

整形外科

Academic Significance and Societal Importance of the Research Achievements

サーチュイン遺伝子を軸とする、骨や軟骨の加齢変化の分子メカニズムを解明することにより、予防法、あるいは医療薬開発のもととなる知見を得ることができた。