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2022 Fiscal Year Final Research Report

Identification of specific synovial fibroblast leading to aberrant bone formation and analysis of synoviocyte differentiation

Research Project

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Project/Area Number 20K17447
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54020:Connective tissue disease and allergy-related
Research InstitutionNagoya City University

Principal Investigator

Miura Yoko  名古屋市立大学, 医薬学総合研究院(医学), 研究員 (60563517)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywords関節リウマチ / 骨性強直 / 滑膜線維芽細胞
Outline of Final Research Achievements

The mechanisms of bony ankylosis in rheumatoid arthritis is unknown. We constructed an arthritis model similar to that of human rheumatoid arthritis and found histologically that there are three different cell populations that exhibit osteo-differentiation in pannus. Therefore, we investigated the mechanism of ectopic bone formation in this study. Synovial fibroblasts were isolated from arthritis model pannus and cultured for 1 week. Synovial fibroblasts were examined by CD146 and CD140a on a Flow cytometer, and four different populations were collected: CD146high positive, CD146mid positive, CD140a positive, and all negative. qPCR revealed that the CD146mid population had elevated gene expression of Col10a1, Runx2, and Sox9 compared to the other populations. This suggested that the CD146mid population may be the pannus fibroblast with the most hypertrophic chondrocyte-like phenotype identified in the histology.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

これまで、関節リウマチや変形性関節症を含む関節疾患は、関節局所でのパンヌスの形成や骨破壊等が知られ、炎症終焉時には異所的な骨性強直 (骨過形成) を生じるが、パンヌス形成から骨破壊に至る過程には不明点が多かった。本研究では、関節炎モデル由来パンヌスの滑膜線維芽細胞を用いて、骨分化状況下にある細胞集団を同定した。関節リウマチでは免疫を主体とした研究が主に行われてきたが、本研究の成果は関節リウマチ研究の新たな学術的領域に貢献したと考えられる。また、CD146陽性集団を治療ターゲットとした炎症時からの治療介入は、その後生じる骨性強直を抑制できると予想され、社会的意義も大きい。

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Published: 2024-01-30  

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