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

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, Koichi Masuda, Toshifumi Ozaki, Hiroshi Asahara

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31 Citations (Scopus)

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.

Original languageEnglish
Article number12503
JournalNature communications
Volume7
DOIs
Publication statusPublished - Aug 16 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Nakamichi, R., Ito, Y., Inui, M., Onizuka, N., Kayama, T., Kataoka, K., Suzuki, H., Mori, M., Inagawa, M., Ichinose, S., Lotz, M. K., Sakai, D., Masuda, K., Ozaki, T., & Asahara, H. (2016). Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs. Nature communications, 7, [12503]. https://doi.org/10.1038/ncomms12503