Mechanism of chondrocyte senescence mediated by CCN3

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18601
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57050:Prosthodontics-related
• Research Institution: Okayama University
• Principal Investigator: Kuwahara Miho 岡山大学, 医歯薬学域, 助教 (30868287)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 加齢 / 細胞老化 / CCN3

Outline of Final Research Achievements

In this study, we showed a positive correlation between age and the expression level of CCN3 in primary human articular chondrocytes. The CCN3 expression levels was upregulated by inducing cellular senescence also. In addition, degenerative changes were observed in the articular cartilage of cartilage-specific CCN3 overexpressing mice, and increased production of cell senescence-associated secretory trait (SASP) factors was confirmed. Furthermore, analysis of promoter gene assay suggests that CCN3 increases p21 activity via induction of p53.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果は、加齢に伴いCCN3発現が誘導されるだけでなく、CCN3の過剰発現により軟骨組織の変性を誘発することを示している。またCCN3の細胞周期調節因子への影響を明らかにし、軟骨細胞老化におけるCCN3の新たな役割を提示した点で学術的な意義がある。さらに今回の成果は、加齢性の変形性関節症発祥の病態解明の一助にもなると考えられ、その社会的な意義も大きい。