Runx2 is required for postnatal intervertebral disc tissue growth and development

J Cell Physiol. 2019 May;234(5):6679-6687. doi: 10.1002/jcp.27410. Epub 2018 Oct 20.

Abstract

Runx2 plays an essential role in embryonic disc tissue development in mice. However, the role of runt-related transcription factor 2 (Runx2) in postnatal disc tissue growth and development has not been defined. In the present studies, we generated Runx2 conditional knockout (KO) mice (Runx2Agc1ER ), in which Runx2 was deleted in Aggrecan-expressing cells in disc tissue at postnatal 2-weeks of age. We then analyzed changes in disc tissue growth and development using histology and immunohistochemical methods in 3-month-old mice. We found that large vacuolated notochordal cells were accumulated in the nucleus pulposus (NP) in Runx2 KO mice. The growth plate cartilage tissue in the disc was thicker in Runx2 KO mice. We also found a significant upregulation of Indian hedgehog (Ihh) expression in the cells in NP cells and in annulus fibrosus cells of Runx2 KO mice. These results demonstrated that Runx2 may play an important role in postnatal disc tissue development through interacting with Ihh signaling.

Keywords: Indian hedgehog (Ihh); growth plate (GP) cartilage; intervertebral disc (IVD); notochordal cells; runt-related transcription factor 2 (Runx2).

Publication types

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

MeSH terms

  • Animals
  • Annulus Fibrosus / growth & development*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Chondrocytes / metabolism
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Growth Plate / metabolism
  • Hedgehog Proteins / metabolism
  • Intervertebral Disc / growth & development*
  • Intervertebral Disc / pathology
  • Intervertebral Disc Degeneration / pathology*
  • Mice, Transgenic
  • Nucleus Pulposus / pathology

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Hedgehog Proteins
  • Runx2 protein, mouse