Drug discovery for osteoarthritis with enhanced drug delivery to bone

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12694
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Hokuriku University
• Principal Investigator: Takahashi Tatsuo 北陸大学, 薬学部, 教授 (50445904)
• Co-Investigator(Kenkyū-buntansha): 鈴木 宏一 北陸大学, 薬学部, 准教授 (70257484) ; 佐藤 友紀 北陸大学, 薬学部, 准教授 (30367495)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 変形性関節症 / 軟骨基質 / フラバノン / liquiritigenin / 軟骨細胞 / 滑膜細胞 / 骨指向性

Outline of Final Research Achievements

Osteoarthritis (OA) is a disease caused by the degeneration of articular cartilage, and is a major factor in the decline of quality of life. The purpose of this study is to create a disease-modifying OA treatment drug that has the effect of repairing articular cartilage and to demonstrate its effectiveness. It has been revealed that liquiritigenin (liq), a flavanone, promotes cell proliferation via the estrogen receptor of chondrocytes, and as a result, promotes the formation of cartilage matrix. Verification using OA model mice revealed that liq improved joint lesions in OA model mice, and liq tagged with acidic oligopeptides to enhance bone targeting had a higher therapeutic effect against OA than liq. These results demonstrate the usefulness of liq as a disease-modifying OA treatment drug.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

変形性関節症（OA）は高齢者に好発する慢性の関節疾患であり、痛みを伴うだけでなく関節機能の低下ももたらす。自覚症状のある患者は国内に1000万人いるといわれており、要介護の主要な原因疾患の一つでもあるため、OAの効果的な予防法と治療法の確立が急務の課題である。現在、OAの薬物療法は主に症状を改善するものしかなく、病気の進行を抑える疾患修飾性OA治療薬はない。本研究の成果は、フラバノンのliquiritigeninが疾患修飾性OA治療薬として有用であることを立証し、OA治療の新たな選択肢を増やすものである。