Salinomycin causes dedifferentiation via the extracellular signal-regulated kinase (ERK) pathway in rabbit articular chondrocytes.

Salinomycin (SAL), a monocarboxylic polyether antibiotic isolated from Streptomyces albus, modulates various cellular responses, including proliferation, apoptosis, and inflammation. However, the effect of SAL on the dedifferentiation of chondrocytes remains unclear. Thus, we investigated the effects and regulatory mechanisms of SAL on the dedifferentiation of rabbit articular chondrocytes. Our results indicate that SAL-induced a loss of type II collagen and decreased sulfated proteoglycan levels in a dose- and time-dependent manner, as assessed by western blot analysis and alcian blue staining. Consistent with dedifferentiation, we found that type II collagen expression was decreased and type I collagen and SOX-9 expression was increased using RT-PCR. Immunohistochemical and immunofluorescence staining also indicated dedifferentiation of chondrocytes. SAL treatment activated the mitogen-activated protein (MAP) kinase signaling pathway. Among the MAP kinases, extracellular signal-regulated kinase (ERK) was phosphorylated and translocated into the nucleus from the cytosol following SAL treatment. Inhibition of ERK with PD98059 (PD) rescued the SAL-induced decrease in type II collagen, increase in type I collagen, and reduction in sulfated proteoglycan. Our findings suggest that SAL induces dedifferentiation via the ERK pathway in rabbit articular chondrocytes.