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, Toshihumi Ozaki, Hiroshi Asahara

Research output: Contribution to journalArticle

17 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

Fingerprint

intervertebral disks
Intervertebral Disc
annuli
regeneration
maintenance
Regeneration
Collagen
Maintenance
Homeodomain Proteins
Tissue regeneration
Ligaments
Tendons
Stem cells
mice
Transcription Factors
Genes
Aging of materials
collagens
Defects
Intervertebral Disc Degeneration

ASJC Scopus subject areas

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

Cite this

Nakamichi, R., Ito, Y., Inui, M., Onizuka, N., Kayama, T., Kataoka, K., ... 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

Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs. / Nakamichi, Ryo; Ito, Yoshiaki; Inui, Masafumi; Onizuka, Naoko; Kayama, Tomohiro; Kataoka, Kensuke; Suzuki, Hidetsugu; Mori, Masaki; Inagawa, Masayo; Ichinose, Shizuko; Lotz, Martin K.; Sakai, Daisuke; Masuda, Koichi; Ozaki, Toshihumi; Asahara, Hiroshi.

In: Nature Communications, Vol. 7, 12503, 16.08.2016.

Research output: Contribution to journalArticle

Nakamichi, R, Ito, Y, Inui, M, Onizuka, N, Kayama, T, Kataoka, K, Suzuki, H, Mori, M, Inagawa, M, Ichinose, S, Lotz, MK, 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, vol. 7, 12503. https://doi.org/10.1038/ncomms12503
Nakamichi, Ryo ; Ito, Yoshiaki ; Inui, Masafumi ; Onizuka, Naoko ; Kayama, Tomohiro ; Kataoka, Kensuke ; Suzuki, Hidetsugu ; Mori, Masaki ; Inagawa, Masayo ; Ichinose, Shizuko ; Lotz, Martin K. ; Sakai, Daisuke ; Masuda, Koichi ; Ozaki, Toshihumi ; Asahara, Hiroshi. / Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs. In: Nature Communications. 2016 ; Vol. 7.
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