Heparin potentiates TGF-β1-mediated phosphorylation of SMAD2 during chondrogenesis.

Abstract

Adult mesenchymal stem cells (MSCs) hold great potential in regenerative medicine for treatment of joint diseases such as osteoarthritis (OA). A novel treatment strategy involving the administration of exogenous glycosaminoglycans, specifically heparin and heparan sulfate (HS), to enhance transforming growth factor (TGF)-β1-mediated chondrogenesis in MSCs has been proposed to treat cartilage defects. Yet, the functional interaction between heparin/HS and TGF-β1 has not been established. Our study shows that heparin interacts with TGF-β1. Importantly, we demonstrate that the interaction between heparin and TGF-β1 potentiates the downstream phosphorylation of SMAD2 in the canonical TGF-β1 signaling cascade. These findings enhance current knowledge about the chondrogenic induction potential of heparin on TGF-β1. They also provide new insights in improving current MSC-based therapies and ultimately, the applications of HS as an adjuvant therapy in OA.