2023 Fiscal Year Final Research Report

Elucidation of the pathophysiology of OA fibrosis and establishment of therapeutic methods using innovative imaging technology and single-cell analysis

Research Project

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Project/Area Number	21H03056
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 56020:Orthopedics-related
Research Institution	Ehime University
Principal Investigator	Imamura Takeshi 愛媛大学, 医学系研究科, 教授 (70264421)
Co-Investigator(Kenkyū-buntansha)	川上良介愛媛大学, 医学系研究科, 准教授 (40508818) 齋藤卓愛媛大学, 医学系研究科, 講師 (60588705)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	イメージング技術 / 変形性関節症 / 線維化
Outline of Final Research Achievements	In order to develop new techniques to elucidate the pathogenesis of tissue fibrosis associated with chronic inflammation in osteoarthritis (OA) and to discover novel diagnostic and therapeutic methods, we developed a high-resolution two-photon excitation fluorescence microscope and a wide-field, high-speed two-photon excitation light sheet microscope, and analyzed the spatial expression of mouse ColI-positive fibroblasts, CAR cells, and THY1-positive fibroblasts. In addition, we developed an analysis system including polarization direction imaging as a system for quantification and quantification of tissue morphology patterns by SHG, and succeeded in quantifying them. Furthermore, machine learning was applied to discriminate mammary tumors. The ligamentectomy OA model were established, and CAR cells and THY1-positive fibroblasts in OA articular cartilage were examined, but expression was not confirmed.
Free Research Field	分子生物学
Academic Significance and Societal Importance of the Research Achievements	変形性関節症（OA）は、関節軟骨の変性・変形によりQOLが大きく制限される疾患である。本邦における膝OAだけでも潜在的な患者数は約3000万人以上と推定されている。OAの原因は未だ不明でその根本的な治療法はない。本研究によって、OAの慢性炎症に伴う組織線維化の研究技術プラットフォームが開発されれば、新たな切り口でOAの原因に迫ることができ、その学術的意義は大きい。さらに、OAの慢性炎症に伴う線維化に関わる多様な細胞の新たなサブタイプが同定され、さらにその時空間制御に関わる細胞間ネットワークが明らかになれば、OAの新たな病態解明、さらに新規診断・治療法の開発に繋がり、その社会的意義も大きい。