IL-1 and TLR signals play an important role in mechanical stress-induced osteoarthritis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Keio University
• Principal Investigator: NIKI Yasuo 慶應義塾大学, 医学部(信濃町), 准教授 (10276298)
• Co-Investigator(Kenkyū-buntansha): 福原 悠介 慶應義塾大学, 医学部(信濃町), 助教 (60594645) ; 宇田川 和彦 慶應義塾大学, 医学部(信濃町), 助教 (70528364)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: メカニカルストレス / 三次元軟骨モデル / IL-1 / TRPV4

Outline of Final Research Achievements

We made a three-dimensional cartilage construct. ATDC5 cells were cultured in alginate beads and seeded within collagen scaffold. Cyclic compressive loading was applied to the cartilage constructs using a cyclic load bioreactor. The mRNA levels of ADAMTS4 and IL-1R1 were substantially increased by the excessive compressive stress. Compressive stress plus subtle level of IL-1β upregulated ADAMTS4 and IL-1R1 expressions. TRPV4 regulated ADAMTS4 and IL-1R1 mRNA levels by cyclic compressive stress. The expression of the IL-1R1 on the surface of chondrocytes would be stimulated by compressive mechanical stress, and subsequent increment of IL-1 susceptibility would be implicated in the OA pathology. TRPV4 channel regulation is one of the most important mechanosensor that controls IL-1 susceptibility and prevents development of OA.

Free Research Field

整形外科　膝関節　関節リウマチ