2021 Fiscal Year Final Research Report

Exploration for the mechanism(s) underlying pain generation and disease progression in osteoarthritis through the analysis of human samples obtained during flare condition.

Research Project

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Project/Area Number	19K09590
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	Iwasawa Mitsuyasu 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)
Co-Investigator(Kenkyū-buntansha)	福井尚志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) 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)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	変形性関節症 / 滑膜 / ウロキナーゼ
Outline of Final Research Achievements	This project was conducted to dissect the pathology of synovial changes in osteoarthritis through the analyses of synovial fluid (SF) samples collected from osteoarthritic knee joints which underwent synovial flare. In each knee, the SF samples were obtained twice, during flare and after the resolution of flare, and these two samples were analyzed in pairs. In results, the concentrations of MMPs-1, 2, 3, urokinase, α2-plasmininhibitor-plasmin complex and D-dimer were found to be elevated during flare compared to those obtained after the flare, while the concentrations of tissue-type plasminogen activator and PAI-1 changed little during the two points of time. These results suggested the occurrence of enhanced fibrinolysis during flare, possibly induced by urokinase. However, the mechanism(s) underlying the rise in urokinase concentration or the occurrence of fibrinolysis during flare were not determined in this project, which were remained to be answered in future.
Free Research Field	整形外科
Academic Significance and Societal Importance of the Research Achievements	変形性関節症は社会の高齢化とともに患者数が増加している疾患であるが、その病態には不明な点が多く、疾患の発症や進行を抑止しうる治療法は確立されていない。本研究では変形性関節症において疾患の進行や症状の発現に大きな役割を果たすことが明らかになってきた滑膜病変について、その病的機序の詳細を解明するために研究を行った。本研究では一定の知見が得られたもののまだ未解明の点も多く残り、その成果が直接疾患の治療に役立つわけではない。しかし本研究で得られた知見は、変形性関節症における滑膜病変を解明するうえで有用なものであって、今後変形性関節症の病態研究を進めるうえで重要な基礎的知見となりうると考えられた。