TGF-beta Signaling in Chondrocyte Terminal Differentiation and Osteoarthritis: Modulation and Integration of Signaling Pathways Through Receptor-Smads

Overview

Journal Osteoarthritis Cartilage

Specialties Orthopedics
Rheumatology

Date 2009 Jul 9

PMID 19583961

Citations 126

Authors

P M van der Kraan

E N Blaney Davidson

A Blom

W B van den Berg

Affiliations

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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.

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