Development of a novel therapeutic approach for rheumatoid arthritis using a newly designed NF-kB inhibitory peptide.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16708
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Osaka University
• Principal Investigator: Etani Yuki 大阪大学, 医学部附属病院, 医員 (60898930)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 変形性関節症 / NF-κB / ペプチド製剤 / 軟骨保護

Outline of Final Research Achievements

① Treatment involving medial meniscal destabilization resulted in observed subchondral bone sclerosis on microCT imaging and cartilage erosion on histological examination at 8 weeks postoperatively. In the medial meniscal destabilization model mice, intra-articular administration of MTI-Ⅱ peptide was performed; however, inflammatory reactions in soft tissues, including synovitis centered around the injection site, were observed, and no protective effect on cartilage tissue was observed.
② Addition of LPS to the ATDC5 chondrocyte cell line led to an increase in MMP-3 and MMP-13, enzymes involved in cartilage protein degradation. Subsequently, when 3mg/ml of MTI-Ⅱ peptide was added to the cells along with 10ng/ml LPS and cultured for 24 hours, a decrease in the expression of MMP-3 and MMP-13 was observed.

Free Research Field

変形性関節症、関節リウマチ、骨粗鬆症

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会において変形性膝関節症の患者数は約2530万人を数え、かつ増加傾向である。既存のNSAIDsの内服・外用や、ヒアルロン酸関節内投与は一定の鎮痛効果が認められるが病状の進行抑制には効果が不十分であり、ステロイド関節内投与は軟骨壊死の懸念があることより新規治療薬の開発が待望されている。転写因子Nuclear factor kappa B（NF-κB）は変形性関節症においては疼痛や病状を悪化させる。本研究は新規開発されたNF-κB阻害ペプチド：MTI-Ⅱペプチドの効果を検討した。MTI-Ⅱペプチドは軟骨分解酵素の発現を抑制しており、変形性関節症予防の新規治療法として期待される。