Elucidation pathophysiology of osteoarthritis - interaction between chondrocytes and osteocytes in subchondoral bone-.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16673
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hokkaido University
• Principal Investigator: Hamasaki Masanari 北海道大学, 大学病院, 医員 (60880044)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨細胞 / 軟骨下骨 / 軟骨細胞 / 変形性関節症 / 炎症性細胞死

Outline of Final Research Achievements

I found that co-culture of degenerated chondrocytes and osteocytes induced cell death of osteocytes.
gene express analysis revealed that pyrolysis, an inflammatory cell death process, is induced in osteocytes. In vitro, in a mouse model of osteoarthritis (OA), the number of osteocytes decreased in subchondral bone and the number of GSDMD or Caspase1 positive osteocytes, which are proteins related to pyrolysis, compared to the control group. These results indicated that osteocyte pyroptosis signaling is enhanced in OA subchondral bone, and that chondrocyte-derived factors in articular cartilage exposed to excessive stress may contribute to the enhancement of these signals.

Free Research Field

変形性関節症

Academic Significance and Societal Importance of the Research Achievements

変形性関節症(OA)は、関節内組織の変性、骨形態の変形、関節痛を主訴とする関節疾患である。関節の変形や運動痛、可動域制限等により、起立や歩行などの日常生活動作に大きな影響を与える。現在のところ根本的な治療法は存在せず、疾患の進行予防が喫緊の課題である。本研究による知見は、OA進行予防に対する治療薬開発のためのターゲット分子の同定に繋がり、今後の治療方法に変革をもたらす事が期待される。