TGF-β3 Signaling in Redifferentiating Passaged Human Articular Chondrocytes

Bioengineering articular cartilage for the repair of damaged cartilage is one approach to biological joint repair. TGF-β3 has been shown to promote articular cartilage tissue formation by dedifferentiated passaged human chondrocytes. We hypothesize that TGF-β3 signals through both ALK1 and ALK5 in passaged human chondrocytes, to induce cartilage tissue formation in vitro. Treatment of passaged chondrocytes in 3D-culture with 10ng/ml TGF-β3 resulted in increased ALK5 expression and decreased ALK1 expression. This correlated with chondrocyte redifferentiation, as shown by increased gene expression of type II collagen and aggrecan, and tissue formation including increased collagen synthesis and retention of newly synthesized proteoglycans and collagen. This study identified that TGF-β3 promotes redifferentiation and ECM accumulation in passaged OA chondrocytes in part by signaling through both the canonical (ALK1 and ALK5) and the non-canonical (TAK1 and p38) pathways, though it is a complex regulation. Collagen production appears to be modulated through the ALK1/ALK5-TAK1-p38 axis.M.Sc