Exploration of the mechanisms underlying synovial changes in osteoarthritic through comprehensive analysis of signal transduction pathways.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
• Principal Investigator: Fukui Naoshi 独立行政法人国立病院機構(相模原病院臨床研究センター), 政策医療企画部, 特別研究員 (10251258)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 変形性関節症 / 滑膜

Outline of Final Research Achievements

In this study, signal transduction mechanisms underlying expression of various proteinases in osteoarthritic (OA) synovium were explored by semi-comprehensive analysis using antibody arrays. Through the analysis of human OA synovium, we obtained results indicating that intracellular signal pathways involving Akt, c-Jun and ERK could be involved in the expression of MMPs-1 and 3 in OA synovium. This result supported our hypothesis that these proteinases are expressed together by activated synovial fibroblasts in OA synovium; fibroblasts are known to express MMPs-1 and 3 abundantly when activated in response to the change in the surrounding matrix via integrins. The result also suggested that other mechanisms are likely involved in the induction of those MMP expression. We also explored signal pathways involved in the expression of urokinase in OA synovium, but could not obtain significant results in the given research term.

Free Research Field

整形外科学関節疾患

Academic Significance and Societal Importance of the Research Achievements

最近の疫学研究によってOAにおいても滑膜病変が症状、とくに痛みの出現と軟骨基質の変性・消失の両方に深く関係していることが明らかになってきた。しかし今のところOAにおいてなぜ滑膜に変化が生じるのかは明らかになっていない。本研究の最終的な目的はOAの滑膜病変を解明し、滑膜病変を改善するための治療法を見出すことであった。今回の研究の結果からOAの滑膜で大量に産生され、関節液を介して軟骨変性に関与すると考えられるMMP-1、３の発現機序について若干の知見を得ることができた。今後さらに知見を積むことでOAにおける滑膜病変を軽減する手法が確立されることが期待される。