Figure 1From: A role for age-related changes in TGFβ signaling in aberrant chondrocyte differentiation and osteoarthritisAlterations in transforming growth factor beta signaling cause changes in chondrocyte differentiation and osteoarthritis development. Transforming growth factor beta (TGFβ) can either signal by the Smad2/3 route (canonical) or the Smad1/5/8 route. Smad2/3 and Smad1/5/8 form a complex with Smad4 that enters the nucleus and modulates gene expression and Runx2 function. The signaling by Smad2/3 and Smad1/5/8 is differentially modified by a number of intracellular molecules. Both Smad routes are blocked by Smad7, while Smad6 blocks preferentially the Smad1/5/8 pathway [100, 101]. wnt signaling modifies these pathways by stabilization of Smad1/5/8 [102]. Smurf1 and Smurf2 are E3 ubiquitin ligases that inhibit Smad signaling. Smurf1 triggers the degradation of Smad1/5/8 while Smurf2 stimulates mainly the degradation of Smad2/3 [103]. Mitogen-activated protein kinases (MAPKs) modulate the stability and degradation of the Smads by phosphorylation of these molecules [102].Back to article page