NADPH oxidase-dependent degradation of hyaluronan in cartilage degenerative diseases

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K17155
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57050:Prosthodontics-related
• Research Institution: Showa University
• Principal Investigator: Inoue Sakie 昭和大学, 歯学部, 兼任講師 (20783252)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 変形性関節症 / NADPHオキシダーゼ / モノカルボン酸トランスポーター / 酸素分圧 / 軟骨細胞

Outline of Final Research Achievements

Osteoarthritis (OA) is a disease caused by aging or excessive mechanical stimulation of joints. OA is characterized by chondrocyte cell death and extracellular matrix loss in articular cartilage. We had shown that NADPH oxidase is involved in the induction of chondrocyte cell death and extracellular matrix degradation induced by interleukin-1β (IL-1β), one of the cytokines which are known to be involved in the pathogenesis of OA. Articular cartilage has a very low partial pressure of oxygen, especially in the deep part of the cartilage, which is less than 1%, due to the lack of oxygen supply from blood vessels. In this study, we found that the expression of NADPH oxidase in chondrocytes after IL-1β stimulation is dependent on the partial pressure of oxygen and that monocarboxylate transporter 1 is involved in this process.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

国内の変形性関節症(OA)は、自覚症状を有する患者だけで1000万人に達する。OAの発症予防や治療法の開発は重要な課題である。OAでは、関節軟骨の基質成分の減少と軟骨細胞死が起こる。これらの変性は関節軟骨表層から始まる。関節軟骨には血管が走行せず、酸素分圧は表層で6%、深層では1%以下と言われる。本研究で、軟骨細胞死と軟骨基質減少に重要な役割を果たすNADPHオキシダーゼの発現とそれに必要なモノカルボン酸トランスポーター1の発現が酸素分圧に依存することを発見した。これは、OAの発症機序の解明と治療・予防法の開発に重要な情報といえる。