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Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes

Author

Listed:
  • Hiroshi Kobayashi

    (Faculty of Medicine, The University of Tokyo)

  • Song Ho Chang

    (Faculty of Medicine, The University of Tokyo)

  • Daisuke Mori

    (Faculty of Medicine, The University of Tokyo
    Faculty of Medicine, The University of Tokyo)

  • Shozo Itoh

    (Faculty of Medicine, The University of Tokyo)

  • Makoto Hirata

    (Faculty of Medicine, The University of Tokyo)

  • Yoko Hosaka

    (Faculty of Medicine, The University of Tokyo
    Faculty of Medicine, The University of Tokyo)

  • Yuki Taniguchi

    (Faculty of Medicine, The University of Tokyo)

  • Keita Okada

    (Faculty of Medicine, The University of Tokyo)

  • Yoshifumi Mori

    (Faculty of Medicine, The University of Tokyo)

  • Fumiko Yano

    (Faculty of Medicine, The University of Tokyo
    Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo)

  • Ung-il Chung

    (Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo)

  • Haruhiko Akiyama

    (Gifu University)

  • Hiroshi Kawaguchi

    (Faculty of Medicine, The University of Tokyo
    Tokyo Shinjuku Medical Center, Japan Community Health Care Organization)

  • Sakae Tanaka

    (Faculty of Medicine, The University of Tokyo)

  • Taku Saito

    (Faculty of Medicine, The University of Tokyo
    Faculty of Medicine, The University of Tokyo)

Abstract

In vitro studies have shown that Rela/p65, a key subunit mediating NF-κB signalling, is involved in chondrogenic differentiation, cell survival and catabolic enzyme production. Here, we analyse 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 including Pik3r1. During skeletal development, homozygous knockout of Rela leads to impaired growth through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela does not alter growth. 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.

Suggested Citation

  • Hiroshi Kobayashi & Song Ho Chang & Daisuke Mori & Shozo Itoh & Makoto Hirata & Yoko Hosaka & Yuki Taniguchi & Keita Okada & Yoshifumi Mori & Fumiko Yano & Ung-il Chung & Haruhiko Akiyama & Hiroshi Ka, 2016. "Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13336
    DOI: 10.1038/ncomms13336
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    Cited by:

    1. Kosei Nagata & Hironori Hojo & Song Ho Chang & Hiroyuki Okada & Fumiko Yano & Ryota Chijimatsu & Yasunori Omata & Daisuke Mori & Yuma Makii & Manabu Kawata & Taizo Kaneko & Yasuhide Iwanaga & Hideki N, 2022. "Runx2 and Runx3 differentially regulate articular chondrocytes during surgically induced osteoarthritis development," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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