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Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs

Author

Listed:
  • Ryo Nakamichi

    (Tokyo Medical and Dental University
    Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences)

  • Yoshiaki Ito

    (Tokyo Medical and Dental University)

  • Masafumi Inui

    (National Research Institute for Child Health and Development)

  • Naoko Onizuka

    (National Research Institute for Child Health and Development)

  • Tomohiro Kayama

    (Tokyo Medical and Dental University)

  • Kensuke Kataoka

    (Tokyo Medical and Dental University)

  • Hidetsugu Suzuki

    (Tokyo Medical and Dental University)

  • Masaki Mori

    (Tokyo Medical and Dental University)

  • Masayo Inagawa

    (National Research Institute for Child Health and Development)

  • Shizuko Ichinose

    (Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University)

  • Martin K. Lotz

    (The Scripps Research Institute)

  • Daisuke Sakai

    (Surgical Science, Tokai University School of Medicine)

  • Koichi Masuda

    (University of California, San Diego)

  • Toshifumi Ozaki

    (Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences)

  • Hiroshi Asahara

    (Tokyo Medical and Dental University
    National Research Institute for Child Health and Development
    The Scripps Research Institute
    CREST from Japan Agency for Medical Research and Development)

Abstract

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx−/− mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration.

Suggested Citation

  • Ryo Nakamichi & Yoshiaki Ito & Masafumi Inui & Naoko Onizuka & Tomohiro Kayama & Kensuke Kataoka & Hidetsugu Suzuki & Masaki Mori & Masayo Inagawa & Shizuko Ichinose & Martin K. Lotz & Daisuke Sakai &, 2016. "Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12503
    DOI: 10.1038/ncomms12503
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