Functional analysis of molecular chaperones in knee osteoarthritis and their therapeutic application

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16744
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kumamoto University
• Principal Investigator: Hisanaga Satoshi 熊本大学, 大学院生命科学研究部(医), 特任助教 (30827308)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 変形性膝関節症 / 小胞体ストレス

Outline of Final Research Achievements

increased expression of molecular chaperone-related genes has been confirmed in cartilage from patients with osteoarthritis of the knee, and single-cell RNA sequencing identified the chondrocyte group involved in maintaining cellular homeostasis in a cluster close to normal cartilage, in which endoplasmic reticulum stress-related genes, including chaperones, were elevated. Furthermore, cell lineage analysis revealed a cell group in which endoplasmic reticulum stress-related genes were elevated during the process of progression from normal cartilage to OA cartilage, and in this cell group, expression of COL2A was reduced. In other words, during the transition from normal cartilage to OA cartilage, protein folding function is reduced, causing a decrease in the ability to produce extracellular matrix, suggesting that this is one of the factors contributing to the progression of OA.

Free Research Field

変形性膝関節症

Academic Significance and Societal Importance of the Research Achievements

変形性関節症は高齢者の健康寿命の延伸を阻害する代表的な運動器疾患である。軟骨破壊の進行を抑制する原因療法の開発が急務となっており、そのためには軟骨変性病態の分子メカニズムの解明による治療標的分子の同定が不可欠である。今回正常軟骨が変性する過程で小胞体に負荷がかかり、病態進行の一因となっている可能性が示唆された。今後その過程での薬剤による小胞体の負荷の軽減により進行予防が期待できる可能性がある。