Expression of hyaluronan-degrading enzymes in osteoarthritic synovium is involved in the hyaluronan degradation in synovial fluids

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18075
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Juntendo University
• Principal Investigator: Shiozawa Jun 順天堂大学, 医学部, 非常勤助教 (30868857)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 変形性膝関節症 / 細胞外マトリックス代謝 / ヒアルロン酸-アグリカンネットワーク分解 / HYBID / TMEM2 / ADAMTS

Outline of Final Research Achievements

Osteoarthritis (OA) of the knee, the most common joint disease, is considered to be a slowly progressive degenerative condition caused by mechanical stress. Although hyaluronic acid (HA)-aggrecan network degradation in articular cartilage and hyaluronan degradation in joint fluid play important roles in the onset and progression of OA articular cartilage destruction, the detailed molecular mechanisms remain unclear. In this study, we demonstrate that recently discovered novel hyaluronan-degrading enzymes (HYBID and TMEM2) and the aggrecan-degrading enzyme（ADAMTS）play essential roles in OA articular cartilage destruction.

Free Research Field

変形性膝関節症

Academic Significance and Societal Importance of the Research Achievements

本研究では、膝OA滑膜組織や関節軟骨組織で過剰産生されたHYBIDとADAMTS4が、関節軟骨中HA－アグリカンネットワークや関節液中HA分解に寄与し、OA関節軟骨破壊に必須であることを証明した。これらの研究成果は、HYBIDの活性阻害剤開発や、アグリカン分解酵素のADAMTS4に対するヒト型抗体の臨床応用により、OA進展抑制に繋がる可能性を示唆しており、膝OAに対する新規治療法開発に繋がることが期待される。