Transforming growth factor-βl induces type II collagen and aggrecan expression via activation of extracellular signal-regulated kinase 1/2 and Smad2/3 signaling pathways

Transforming growth factor (TGF)-beta regulates the anabolic metabolism of articular cartilage and prevents cartilage degradation. TGF-beta 1 influences cellular proliferation, differentiation and the extracellular matrix through activation of the extracellular signal-regulated kinase (ERK)1/2 and Smad2/3 signaling pathways. However, it has remained to be fully elucidated precisely how the ERK1/2 and Smad2/3 signaling pathways mediate anabolic processes of articular cartilage. The present study investigated how ERK1/2 and Smad2/3 signaling mediate TGF-beta 1-stimulated type II collagen and aggrecan expression in rat chondrocytes. The results confirmed that TGF-beta 1 stimulates type II collagen and aggrecan expression in rat chondrocytes, and furthermore, that the ERK1/2 and Smad2/3 signaling pathways were activated by TGF-beta 1. Conversely, the TGF-beta receptor I (ALK5) kinase inhibitor SB525334 significantly impaired TGF-beta 1-induced type II collagen and aggrecan expression, coinciding with a reduction of ERK1/2 and Smad3 phosphorylation. In addition, TGF-beta 1-induced type II collagen and aggrecan expression were significantly suppressed by ERK1/2 inhibitor PD98059. Similarly, TGF-beta 1-stimulated type II collagen and aggrecan expression were decreased in the presence of a Smad3 phosphorylation inhibitor SIS3. Therefore, the present study demonstrated that the ERK1/2 and Smad2/3 signaling pathways regulate type II collagen and aggrecan expression in rat chondrocytes.