Elucidating mechanisms of cartilage matrix destruction via DNA methylation

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10882
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Tohoku University
• Principal Investigator: Hashimoto Ko 東北大学, 医学系研究科, 講師 (00718497)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 変形性関節症 / 軟骨基質破壊 / 網羅的遺伝子解析

Outline of Final Research Achievements

In this study, exhaustive gene expression analysis of approximately 24,500 genes were conducted of human cartilage pieces from femoral heads harvested from surgeries for patients with femoral neck fracture (non-osteoarthritic: non-OA group) and secondary osteoarthritis (OA group). DPT, IGFBP7, FOXO1 and KLF2 were the genes identified as the new OA-related genes as they were highly expressed in chondrocytes of Japanese hip OA compared to non-OA. Out of overexpressed genes in OA, only 10% of the genes were common between Japanese and western population. Our study elucidated the difference in gene expression patterns of OA chonderocytes between Japanese and western population although the phenotype of OA is similar between different ethnic origins.

Free Research Field

軟骨代謝・脊椎外科

Academic Significance and Societal Importance of the Research Achievements

本研究により、従来報告があった欧米人のOAにおける軟骨細胞の形質と、日本人のOAにおける形質が異なることが示された。また日本人のOA軟骨細胞に特異的と考えられる遺伝子発現パターンが見つかり、今後日本人に特化したOAの病態解明や治療ターゲットとなり得る遺伝子群を発見することができた。今回新たに発見された遺伝子群の機能解析を進めることで、日本人におけるOAの発症や病態進行のメカニズムを解明する一助となる可能性がある。またこれらの遺伝子群が発現するタンパクの機能解析の結果如何によっては、従来不可能であったOAに対する根治的・根本的な治療介入への可能性が示唆される。