Elsevier

Osteoarthritis and Cartilage

Volume 17, Issue 12, December 2009, Pages 1539-1545
Osteoarthritis and Cartilage

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

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Summary

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.

Key words

TGF-beta
Smads
Chondrocytes
Runx2
Osteoarthritis

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