Elucidation of a new chondrocyte aging control mechanism mediated by CCN3 in osteoarthritis of the hip

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16686
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Okayama University
• Principal Investigator: Yamada Kazuki 岡山大学, 医歯薬学域, 助教 (50756088)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: hip osteoarthritis / cartilage / TNFα / IL-6 / p16 / ADAMTA4/5 / CCN3 / CCN ファミリー遺伝子

Outline of Final Research Achievements

Based on the hypothesis that increased expression of CCN3 induces osteoarthritis of the hip (OA), we aimed to analyze the relationship between aging, weight bearing, and CCN3 expression, which are considered to be factors in the pathogenesis of OA, and cartilage degeneration using femoral head cartilage tissue. In human hip joint cartilage tissue, regardless of whether weight bearing was performed or not, a significant increase in OA-related factors and CCN3 mRNA was observed in the OA group. The same result was observed in histological stain. A positive correlation was also observed between CCN3 mRNA and the Mankin score of the adjacent tissue. Joint degeneration was observed early in the femoral head of CCN3 Tg mice, and gene expression and immunohistochemistry revealed significant increases in the expression of CCN3 and OA-related markers in primary cultured chondrocytes of the femoral head.

Free Research Field

股関節外科

Academic Significance and Societal Importance of the Research Achievements

本研究より、変形性股関節症の有無、さらには重症度とCCN3の発現には相関があるが、年齢やメカニカルストレスとにはないことが示唆され、股関節の軟骨細胞におけるCCN3を介した関節変性に関する分子メカニズムの一部が解明された。本研究結果により、変形性股関節症の発生と進行防止に対する新しい治療法の確立につながる可能性があると考えられる。