Age-dependent alteration of TGF-β signalling in osteoarthritis

Cell Tissue Res. 2012 Jan;347(1):257-65. doi: 10.1007/s00441-011-1194-6. Epub 2011 Jun 4.

Abstract

Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling might trigger the differentiation of articular chondrocytes with an autolytic phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activin Receptors, Type II / metabolism
  • Aging / physiology*
  • Cell Differentiation / physiology
  • Chondrocytes / cytology
  • Chondrocytes / physiology
  • Fibrosis / pathology
  • Humans
  • Osteoarthritis / pathology
  • Osteoarthritis / physiopathology*
  • Osteoarthritis / therapy
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction / physiology*
  • Smad Proteins / metabolism
  • Synovial Membrane / pathology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • ACVRL1 protein, human
  • Activin Receptors, Type II
  • Receptor, Transforming Growth Factor-beta Type I
  • TGFBR1 protein, human