The MEK-ERK1/2 signaling pathway regulates hyaline cartilage formation and the redifferentiation of dedifferentiated chondrocytes in vitro.

ABSTRACT

The aim of this study was to investigate the role of the mitogen-activated protein kinase kinase-extracellular signal-regulated kinases 1/2 (MEK-ERK1/2) signaling pathway in chondrocyte differentiation and cartilage tissue construction in vitro. Chondrocytes were stimulated with rat serum (RS) and fetal bovine serum (FBS), and chondrocyte phenotypes were investigated microscopically. Chondrocyte proliferation was analyzed using fluorescence activated cell sorting (FACS) and the CCK8 method. Protein and mRNA expressions were assessed by western blot and RT-qPCR. Constructed cartilage tissues were examined by Safranin O-Fast Green FCF staining and immunofluorescence. In contrast to FBS, RS induced rapid dedifferentiation of chondrocytes and decreased type II collagen expression and proteoglycan synthesis. ERK1/2 and type I collagen expression increased during dedifferentiation and decreased during redifferentiation. Increased MEK-ERK1/2 pathway activity resulted in chondrocyte dedifferentiation, and inhibition of ERK1/2 by the inhibitor PD0325901 reversed dedifferentiation and led to redifferentiation. These data suggest strongly that inhibition of MEK-ERK1/2 activation prevents chondrocyte dedifferentiation and fibrocartilage formation.