OA-related inflammation inhibits protective transforming growth factor-β signaling via post-translational modification of the SMAD2/3 linker region

Abstract

Purpose: Osteoarthritis (OA) is a degenerative joint disease characterized by inflammation and irreversible cartilage damage. The development of OA is associated with dysregulated TGF-β signaling. Via intracellular activation of the transcription factors SMAD2 and SMAD3 this growth factor 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 TGF-β signaling.