Mechanism of maintainace of articular chondrocyte by NF-kB signaling.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Kobayashi Hiroshi 東京大学, 医学部附属病院, 助教 (20407951)
• Co-Investigator(Kenkyū-buntansha): 澤田 良子 東京大学, 医学部附属病院, 病院診療医 (30648308) ; 矢野 文子 東京大学, 医学部附属病院, 特任講師 (80529040)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: NF-kBシグナル / 変形性関節症

Outline of Final Research Achievements

We examined the function of NF-kB signalling in articular chondrocyte both in vitro and in vivo to realize the prevention of degeneration and regeneration of articular chondrocyte . We analyze in vivo functions of Rela in embryonic limbs and adult articular cartilage, and find that Rela protects chondrocytes from apoptosis through induction of anti-apoptotic genes. In articular cartilage, homozygous knockout of Rela at 7 weeks leads to marked acceleration of osteoarthritis through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela results in suppression of osteoarthritis development through inhibition of catabolic gene expression. Haploinsufficiency or a low dose of an IKK inhibitor suppresses catabolic gene expression, but does not alter anti-apoptotic gene expression. The biphasic regulation of chondrocytes by Rela contributes to understanding the pathophysiology of osteoarthritis.

Free Research Field

軟骨代謝