Identifying the Role of GRK-5 in the Pathogenesis of Osteoarthritis and Therapeutic Potential

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16658
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyushu University
• Principal Investigator: Sueishi Takuya 九州大学, 医学研究院, 共同研究員 (40896700)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 変形性膝関節症 / 疾患修飾治療薬 / GRK5 / Amlexanox / ヒアルロン酸

Outline of Final Research Achievements

We aimed to develop a drug for OA disease modification using a GRK5 inhibitor as the active ingredient. In the process, we validated the optimized concentration and dosage of Amlexanox. Furthermore, the use of hyaluronic acid as a solvent for Amlexanox was found to have a synergistic effect on cartilage protection compared to a single agent.
It has been previously reported that meniscus degeneration is closely related to the pathogenesis of knee osteoarthritis, and we tested whether GRK5 is involved in meniscus degeneration. The results suggest that GRK5 does not have anabolic or catabolic effects on meniscus cells in experimental systems using human and mouse meniscus cells. Therefore, we did not proceed to further validation.

Free Research Field

変形性膝関節症

Academic Significance and Societal Importance of the Research Achievements

変形性膝関節症は膝関節の軟骨が変性摩耗する病気で、高齢者の生活の質を低下させる代表的な疾患である。現状の薬物治療は、内服（NSAID、非麻薬性鎮痛薬）と関節内注射（ヒアルロン酸、ステロイド）があるが症候改善薬であり、疾患修飾治療薬はない。
Amlexanoxはすでに他科領域において安全性が確認されており、生産コストの面でも臨床応用しやすいという利点がある。また全く違う分野の疾患の治療に役立てる試みは創造性に富んでいる。GRK5阻害薬（アンレキサノクス）とヒアルロン酸の混合によるOA進行抑制効果は相乗的であり、疾患修飾性ＯＡ治療の候補としてさらなる検証が必要である。