For treatment of knee osteoarthritis with HAS2 transgene

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16655
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Nagoya University
• Principal Investigator: Ishizuka Shinya 名古屋大学, 医学部附属病院, 病院助教 (40813316)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ヒアルロン酸

Outline of Final Research Achievements

We evaluated the effect of methylumbelliferone (4-MU), that we previously showed its anti-inflammatory features in activated osteoarthritic (OA) chondrocytes in vitro, using in vivo model to confirm whether 4-MU was effective at limiting the effects of OA on articular cartilage in vivo. The progression of OA was evaluated after destabilization of the medial meniscus (DMM) surgery on C57BL/6 mice in the presence or absence of 4‐MU‐containing chow. Mice fed 4-MU after DMM surgery exhibited significant suppression of OA starting from an early stage in vivo. Mice fed 4-MU exhibited lower OARSI scores after DMM; reduced osteophyte formation and reduced MMP3 and MMP13 immunostaining. 4-MU also exerted pronounced chondroprotective effects on murine joint cartilage exposed to IL1β in vitro and, blocked IL1β-enhanced lactate production in cartilage explants. We will evaluate HAS2 overexpression effect using similar experimental model.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

変形性膝関節症（膝OA）に対する保存的治療にひとつとして広く行われているヒアルロン酸の関節内投与は頻回の注射の痛み、また感染の危険性などのマイナスな面もある。我々は細胞を用いた実験で後顆が確認されているヒアルロン酸合成酵素の関節内組織、細胞への遺伝子導入による新たな膝OAに対する治療を目指しており、今回の研究成果では膝OAモデルマウスの作成の確立、薬剤の関節内投与による効果の確認、ヒアルロン酸阻害による抗炎症効果までを動物実験で示すことができた。今回の成果をもとにウイルスベクターによる遺伝子導入とそれによる膝OAの進行抑制効果を今後の研究につなげていく予定である。