2017 Fiscal Year Final Research Report
Mechanism of maintainace of articular chondrocyte by NF-kB signaling.
Project/Area Number |
15K10460
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | The University of Tokyo |
Principal Investigator |
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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)
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Project Period (FY) |
2015-04-01 – 2018-03-31
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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.
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Free Research Field |
軟骨代謝
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