TGF-beta signaling in chondrocyte terminal differentiation and osteoarthritis: modulation and integration of signaling pathways through receptor-Smads

Osteoarthritis Cartilage. 2009 Dec;17(12):1539-45. doi: 10.1016/j.joca.2009.06.008. Epub 2009 Jun 26.


Objective: Chondrocytes and alteration in chondrocyte differentiation play a central role in osteoarthritis. Chondrocyte differentiation is amongst others regulated by members of the transforming growth factor-beta (TGF-beta) superfamily. The major intracellular signaling routes of this family are via the receptor-Smads. This review is focused on the modulation of receptor-Smad signaling and how this modulation can affect chondrocyte differentiation and potentially osteoarthritis development.

Methods: Peer reviewed publications published prior to April 2009 were searched in the Pubmed database. Articles that were relevant for the role of TGF-beta superfamily/Smad signaling in chondrocyte differentiation and for differential modulation of receptor-Smads were selected.

Results: Chondrocyte terminal differentiation is stimulated by Smad1/5/8 activation and inhibited the by Smad2/3 pathway, most likely by modulation of Runx2 function. Several proteins and signaling pathways differentially affect Smad1/5/8 and Smad2/3 signaling. This will result in an altered Smad1/5/8 and Smad2/3 balance and subsequently have an effect on chondrocyte differentiation and osteoarthritis development.

Conclusion: Modulation of receptor-Smads signaling can be expect to play an essential role in both the regulation of chondrocyte differentiation and osteoarthritis development and progression.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation
  • Chondrocytes / metabolism*
  • Humans
  • Mice
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteogenesis / genetics
  • Signal Transduction / genetics
  • Smad Proteins, Receptor-Regulated / genetics*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Ubiquitin-Protein Ligases / genetics*
  • Wnt1 Protein / genetics


  • Smad Proteins, Receptor-Regulated
  • Transforming Growth Factor beta
  • Wnt1 Protein
  • Ubiquitin-Protein Ligases