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

Nat Commun. 2016 Aug 16;7:12503. doi: 10.1038/ncomms12503.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Annulus Fibrosus / metabolism
  • Annulus Fibrosus / physiology*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Intervertebral Disc / metabolism
  • Intervertebral Disc / physiology*
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Regeneration*
  • Young Adult

Substances

  • Homeodomain Proteins
  • Mkx protein, human
  • mohawk protein, mouse