Mechanical stress mediates the DNA repair enzyme and energy metabolism in chondrocytes in osteoarthritis.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09492
• 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: St. Marianna University School of Medicine
• Principal Investigator: Kazuo Yudo 聖マリアンナ医科大学, 医学研究科, 教授 (60272928)
• Co-Investigator(Kenkyū-buntansha): 藤井 亮爾 聖マリアンナ医科大学, 医学研究科, 准教授 (10333535) ; 唐澤 里江 聖マリアンナ医科大学, 医学研究科, 准教授 (50434410)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 軟骨代謝 / 細胞エネルギー代謝 / 核酸修復酵素 / 長寿遺伝子関連蛋白

Outline of Final Research Achievements

Recent reports clearly indicate that chronic excess production of reactive oxygen species (ROS) from chondrocytes, which is induced by mechanical force to cartilage, plays an important role in cartilage degeneration occurring after mechanical injury to cartilage in osteoarthritis (OA). Apurinic/apyrimidinic endonuclease 2 (Apex2) is an essential DNA repair enzyme that plays a critical role in DNA repair against the oxidative damage in a variety of human somatic cells. The expression of DNA repair enzyme Apex2 and energy sensor sirtuin 1 in chondrocytes were associated with the degeneration of articular cartilages and was induced by OA-relating catabolic factors. Our findings suggest that DNA repair enzyme and energy metabolic factor may have a potential to prevent the catabolic stress-mediated down-regulation of chondrocyte activity in OA.

Free Research Field

軟骨代謝

Academic Significance and Societal Importance of the Research Achievements

本研究では、メカニカルストレスに応答する「軟骨細胞のDNA損傷修復機構」と「細胞エネルギー代謝の調節因子」の相互作用・ネットワークを詳解してきた。メカニカルストレスに対して、軟骨細胞がどのように応答するか、防御機構はあるのか、軟骨変性機序と荷重ストレス応答との関連については不明な点が多く、この違いを解明することでOAの病因・病態の解明と新規治療法開発の糸口を得る研究を進めていく。これまでに得られた軟骨細胞のDNA修復酵素活性と細胞エネルギー代謝調節因子との関連に関する研究成果を基盤に、軟骨変性の機序を解明して、治療法開発の基盤を確立したいと考えている。