Elucidation of a novel regulatory mechanism of bone metabolism by cellular senescence regulators and its therapeutic application

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09034
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Saga University
• Principal Investigator: Kukita Akiko 佐賀大学, 医学部, 准教授 (30153266)
• Co-Investigator(Kenkyū-buntansha): 馬渡 正明 佐賀大学, 医学部, 教授 (80202357) ; 久木田 敏夫 九州大学, 歯学研究院, 教授 (70150464)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨代謝 / 骨芽細胞 / 骨細胞 / 老化 / 骨粗鬆症 / 転写因子

Outline of Final Research Achievements

We analyzed the role of basic HLH-type transcription factors involved in cellular senescence in bone metabolism and bone aging. bHLH-1 knockout (KO) mice showed increased bone mass and bone formation in femurs, and osteoblasts showed increased proliferation and differentiation of progenitor cells, and increased number of osteocytes. On the other hand, autophagy in osteoblasts was increased whereas apoptosis in osteoblasts and osteocytes was decreased. The bone mass of bHLH-1 KO mice was higher than that of wild type (WT) mice even in old age, and the bone loss due to aging was also reduced. Furthermore, the expression of senescent marker genes was decreased in osteoblasts and osteocytes of bHLH-1 KO mice, suggesting that bHLH-1 may be involved in the accumulation of senescent cells and age-related bone loss.

Free Research Field

骨代謝　分子生物学

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会に伴い骨粗鬆症や変形性関節症などの骨・関節疾患の患者数が増加している。近年、このような加齢に関連する疾患において、複製やストレスなどの刺激で形成した老化細胞の蓄積が病態の原因となることが報告されている。本研究では老化細胞の制御機能が知られているbHLH型転写因子が、老化した骨で老化細胞の蓄積に関わる可能性を初めて明らかにした。本研究で得た知見は、骨・関節疾患の治療法の開発などの研究に将来的に寄与するものと考えられる。