TGF-β signaling plays an essential role in the growth and maintenance of intervertebral disc tissue

FEBS Lett. 2011 Apr 20;585(8):1209-15. doi: 10.1016/j.febslet.2011.03.034. Epub 2011 Mar 21.

Abstract

TGF-β signaling plays a critical role in cartilage and spine tissue development at embryonic stage but its role in postnatal intervertebral disc (IVD) tissue growth and maintenance remain poorly understood. In the present studies, we have deleted the Tgfbr2 gene in inner annulus fibrosus cells of the disc tissue and surrounding growth plate chondrocytes using Col2a1-CreER(T2) transgenic mice. We found that TGF-β signaling is required for normal growth plate cartilage and endplate cartilage growth at postnatal stage. The expression of Mmp13 gene is significantly up-regulated in primary disc cells of Tgfbr2 conditional knockout mice. Deletion of the Mmp13 gene under Tgfbr2 null background completely reverses the abnormal disc phenotype found in Tgfbr2 knockout mice.

Publication types

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

MeSH terms

  • Animals
  • Bone Density Conservation Agents / pharmacology
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Female
  • Growth Plate / cytology
  • Growth Plate / metabolism
  • Histocytochemistry
  • Intervertebral Disc / cytology
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / metabolism*
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Tamoxifen / pharmacology
  • Time Factors

Substances

  • Bone Density Conservation Agents
  • Col2a1 protein, mouse
  • Collagen Type II
  • Receptors, Transforming Growth Factor beta
  • Tamoxifen
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse