Development of a novel disease modifying anti-osteoarthritis drug

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16761
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Amemiya Masaki 東京医科歯科大学, 東京医科歯科大学病院, 特任助教 (00848442)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 変形性関節症 / 疼痛 / CNP / 線維化

Outline of Final Research Achievements

Fibrosis of infrapatellar fat pad (IFP) is closely related to articular cartilage degeneration and persistent pain in knee osteoarthritis (OA). We have reported that C-type natriuretic peptide (CNP) inhibited both cartilage degeneration and persistent pain in a rat knee arthritis model. Based on these results, we examined three aspects in this study: whether CNP exhibits inhibitory effects on persistent pain even when administered after fibrosis of IFP occurs, whether CNP is effective in a traumatic OA model, and the analysis of the molecular mechanisms underlying the pharmacological actions of CNP. We showed that intra-articular injection of CNP has therapeutic effects on persistent pain alleviation when administered after fibrotic changes of IFP has occurred. We also showed that CNP alleviated persistent pain in a rat traumatic OA model. Total RNA Sequencing analyses indicated that CNP has inhibitory effects on the IL6-STAT3 signaling pathway in synovial cells.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、CNPのDMOADsとしての開発の可能性を考察することを主たる目的とする。本研究は、私が現在所属している教室で蓄積されたデータを基に開始された研究であり、独自性は確保されている。また、本研究計画が達成された場合、CNPは世界初のDMOADsとして、創薬開発に進める可能性があり、社会的に大きな影響を与えうる研究に発展できる可能性があると考えている。