Insights into the function of senescent osteoblast in fracture repairing.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20960
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Osaka University
• Principal Investigator: Ukon Yuichiro 大阪大学, 大学院医学系研究科, 招へい教員 (50964334)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 骨代謝 / 骨粗鬆症 / 細胞老化 / 骨老化

Outline of Final Research Achievements

Age-related osteoporosis was characterised by the loss of osteoblast Men1; osteoblast-specific induced KO of Men1 was consistent with the phenotype of patients with age-related osteoporosis. Histomorphologically, femurs from Men1KO mice showed reduced osteoblast activity and increased osteoclast activity, a feature of age-related osteoporosis; Men1 loss induced cellular senescence via activation of mTORC1 and suppression of AMPK, which was restored by metformin treatment. In an ectopic-forming bone model, Men1 deficiency caused senescent cell accumulation and osteoporotic bone formation, which were ameliorated by metformin. In an inhibited fracture repair model, the results suggest the effectiveness of senescent cell removal in pseudoarticular treatment.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

骨粗鬆症は加齢によって生じ、骨における老化と認識されてきた。しかし、実際は複合的な全身性の多因子が交絡し、臨床における骨粗鬆症は必ずしも老化の関与だけではない。このように、骨の老化は知られているが、老化細胞の蓄積による骨への影響は明らかではない。老化細胞は、個体老化だけでなく組織修復にも関与しており、詳細に骨芽細胞の細胞老化の機能や機序が明らかになれば、個体老化に伴う老化細胞の増加に対する治療介入だけでなく、組織修復における老化細胞の調整など新たな創薬ターゲットが多数生まれると期待される。