Fig 1: Schematic of the proposed mechanism whereby Sr affects proliferation and differentiation of bovine chondrocytes via the transforming growth factor ß (TGFß) signaling pathway. Sr shifts the signaling of TGFß1 to SMAD family member 3 (SMAD3) by promoting activin receptor-like kinase 5 (ALK5) expression and inhibiting ALK1 expression. Phosphorylation of SMAD3 and SMAD1/5/9 after binding with SMAD4 transfers them into the nucleus to regulate gene transcription. An increase in pSMAD3 promotes the expression of type ? Collagen a1 (COL2A1) and aggrecan (ACAN). pSMAD1/5/9 induces type ? Collagen a1 (COL10A1), secreted phosphoprotein 1 (SPP1), vascular endothelial growth factor (VEGFA), and alkaline phosphatase (ALPL) by stimulating the function of runt-related transcription factor 2 (RUNX2). The increase in the pSMAD3 can inhibit the function of RUNX2 to decrease the COL10A1, SPP1, and ALPL expression.