2022 Fiscal Year Final Research Report

Elucidation of the synovial pathology in osteoarthritis by focusing on the involvement of fibrinolytic activity and development of pain.

Research Project

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Project/Area Number	20K09447
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56020:Orthopedics-related
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), 外科系リウマチ研究室, 客員研究員 (10251258)
Co-Investigator(Kenkyū-buntansha)	大橋暁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), 外科系臨床研究室, 医長 (20466767) 岩澤三康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), 診療部・整形外科, 部長 (60574093)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	変形性関節症 / 滑膜 / 膝関節 / MMP-1
Outline of Final Research Achievements	In this study, synovial fluid samples obtained from osteoarthritic (OA) knees that underwent synovial flare were analyzed in order to determine the link between synovial pathology and cartilage degeneration. In the results, we found that the enzymic activity of MMP-1, but not that of MMP-2 or MMP-3, was enhanced during flare compared with the samples collected after resolution of flare. This result might explain why rapid cartilage degeneration occurs during flare, at least in a subset of patients. If the enhancement in MMP-1 activity in synovial fluid is a prevalent event across various OA knees, that could account for, at least in part, progression of the disease related to the synovial pathology. This finding might be crucial in understanding the pathology of OA. During this study period, we also found that the enhanced expression of urokinase which occurs in the synovium during flare could be induced by active TGF-β released from OA cartilage.
Free Research Field	整形外科
Academic Significance and Societal Importance of the Research Achievements	膝OAは患者数の極めて多い疾患であるにもかかわらず、疾患の進行を抑止しうる治療法は確立されていない。本研究の結果から、滑膜病変に伴う関節軟骨の変性消失には、関節液中のMMP-1の活性亢進が関与する可能性が示された。もしMMP-1の活性亢進が滑膜性フレアの症例だけでなく膝OAの症例全般について認められる現象であるとすれば、MMP-1の活性抑制によってOAの進行が抑止される可能性も考えられる。OAの効果的な進行抑止法の確立は高齢者の自立喪失の予防の観点からも、また医療経済学的な観点からも重要である。本研究の成果はOAの進行抑止法の確立に繋がりうる点で社会的にも意義の高いものと考えられた。