Molecular mechanisms of locomotor degenerative changes due to crosstalk of aging control factors

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02920
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ASOU YOSHINORI 東京医科歯科大学, 大学院医歯学総合研究科, ジョイントリサーチ講座教授 (50345279)
• Co-Investigator(Kenkyū-buntansha): 辻 邦和 東京医科歯科大学, 大学院医歯学総合研究科, ジョイントリサーチ講座教授 (20323694)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: SIRT6 / PAI-1 / osteoporosis / ageing / FGF23 / SOST

Outline of Final Research Achievements

This year, we crossed Dmp1cre::Sirt6f/f mice (Sirt6cKO) with PAI-1KO mice to generate Dmp1cre::Sirt6f/f;;PAI-1-/- mice (dKO mice) to verify the signal cross-talk between Sirt6 and PAI-1. dKO mice showed reduced FGF 23, and SOST expression was reduced to levels comparable to controls. Aged PAI-1KO mice had more bone mass and higher blood phosphorus levels than wild-type mice of the same week of age. These results indicate that FGF 23 and SOST expression is regulated by SIRT6 and that the mechanism is at least partly mediated by PAI-1 regulation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

我々の成果は、サーチュインアゴニストのニコチンアミドモノヌクレオチドや、経口PAI-1阻害剤などの、加齢に伴う骨代謝の障害に対する治療への応用の可能性を示唆する。