| Project/Area Number |
18K09082
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 変形性膝関節症 / 半月板逸脱 / 骨棘 / HYBID / ヒアルロン酸 / MRI / 軟骨 / ロコモティブシンドローム / 軟骨摩耗 / 軟骨下骨 / 滑膜炎 / 骨髄異常陰影 / Hybid |
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| Outline of Final Research Achievements |
In this study examining pathophysiology of knee osteoarthritis (OA), medial meniscus extrusion (MME) was closely associated with the medial tibial osteophyte width, which was composed of not only bone-part but also cartilage-part. Medial meniscus (MM) was extruded not only medially (MME) but also anteriorly (AME) and AME was also associated with anterior tibial osteophyte width. The change of MME was also associated with that of medial tibial osteophyte width. The cultures chondrocytes extracted from cartilage part of osteophyte were positive for CD105 and CD166 antibody and their expression was inhibited by IL-6. The expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization；KIAA1199), novel hyaluronan-degrading enzyme, is increased in both cartilage and synovium in knee OA patients. HYBID degradates hyaluronan directly and the expression of HYBID was increased by IL-6 in chondrocyte extracted by knee OA patients.
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| Academic Significance and Societal Importance of the Research Achievements |
変形性膝関節症（膝OA）には疾患修飾型治療法は存在せず、病態の更なる解明が急務である。
本研究では、①膝関節の立位単純X線とMRIを備えた国内最大の本学の高齢者住民コホート研究（文京ヘルススタディー：BHS）のデータを用いて、早期から出現し膝OAに重要な役割を担う半月板逸脱(MME)の病態と、②関節軟骨の変性と破壊に深く関与する新規ヒアルロン酸分解酵素・HYBIDとアグリカン分解に関わるADAMTSの機能解析、③MME発生と密接に関連する骨棘の発生機序の解明を進めた。本研究は膝OAの病態解明に確実な一歩となり、膝OAの病態に則した早期診断・早期治療の実現に向けて、社会的意義は大きいと考える。
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