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

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

Author information

1
Experimental Rheumatology & Advanced Therapeutics, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands. p.vanderkraan@reuma.umcn.nl

Abstract

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.

PMID:
19583961
DOI:
10.1016/j.joca.2009.06.008
[Indexed for MEDLINE]
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