Regulation and mechanisms elucidation of synovitis in knee osteoarthritis

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K09083
• 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: Juntendo University
• Principal Investigator: Kaneko Haruka 順天堂大学, 医学部, 准教授 (50445516)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 変形性膝関節症 / 滑膜 / 骨棘 / パールカン / プロテオグリカン / 軟骨下骨 / TGF-β / Smad2

Outline of Final Research Achievements

To develop treatments for knee osteoarthritis (knee OA), it is important to understand the molecular mechanisms of pathophysiology of a wide variety of diseases. In early-stage knee OA, synovitis and osteophytes associated with meniscus extrusion have been shown to be important pathological conditions in the development and progression of the disease. Therefore, we focused our study on synovitis and osteophytes, which are closely related, as osteophytes are formed through a similar process of endochondral ossification via the synovium. We previously reported that perlecan, one of the heparan sulfate proteoglycan (HSPG), is involved in osteophyte formation. In this study, we found that osteophyte maturation was inhibited and synovitis was activated at early stage knee OA by the absence of synovial perlecan in mice.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

健康寿命の延伸や介護にかかる医療経済的問題のため，ロコモティブシンドロームの代表疾患である変形性膝関節症(膝OA)の疾患修飾型治療薬の開発は必須であるが未だ開発されていない．本研究の成果は，早期膝OAにおける臨床上の病態進行に係わる重要な因子である滑膜炎および骨棘に焦点をあて，パールカンという関連因子を同定した．このことは，滑膜や骨棘を治療ターゲットとした早期膝OAに対する疾患修飾型治療薬の開発の一助となることが期待される．