Post-translational modification of the SMAD2/3 linker region: the missing link between osteoarthritis-related inflammation and disturbed transforming growth factor-β signaling

Abstract

Purpose: Osteoarthritis (OA) is a degenerative joint disease characterized by inflammation and irreversible cartilage damage. The development of OA is associated with dysregulated transforming growth factor-β (TGF-β) signaling, e.g. with loss of SMAD2/3 signaling. Via intracellular activation of these transcription factors TGF-β inhibits chondrocyte hypertrophy and expression of cartilage degrading enzymes. Recently, it has been shown that post-translational modification of these SMAD proteins in their linker protein domain can dysregulate their function.