PDGF regulates chondrocyte proliferation through activation of the GIT1- and PLCγ1-mediated ERK1/2 signaling pathway

Abstract

Studies investigating the effects of cytokines on chondrocytes have significant application potential, since the culture of cartilage cells in vitro is a vital step for cartilage tissue engineering. Platelet-derived growth factor (PDGF), one of the growth factors occurring at the early stage of the healing process of damaged tissue, is critical in bone healing. The present study investigated the effects of the activation of PDGF on cell proliferation, apoptosis and the underlying mechanisms of chondrocytes in vitro. The results indicated that the stimulation of PDGF led to overexpression of the G-protein-coupled receptor kinase interacting protein-1 (GIT1) and promotion of the phosphorylation of phospholipase Cγ1 (PLCγ1). Furthermore, PDGF induced chondrocyte proliferation and inhibited apoptosis via activation of the extracellular signal-regulated kinase (ERK) 1/2 pathway. Following knocking down GIT1 expression by small interfering RNA, phosphorylation of PLCγ1 and activation of the ERK1/2 pathway was no longer promoted by PDGF. In addition, the effects of PDGF on proliferation and apoptosis were suppressed. The expression levels of GIT1 were not affected; however, the phosphorylation of ERK1/2 was suppressed through inhibition of the phosphorylation of PLCγ1 by U73122. The results demonstrated that GIT1 is upstream of PLCγ1. Although the ability of PDGF to induce cell proliferation was inhibited by the inhibition of the ERK1/2 pathway by PD98059, apoptosis was not suppressed. In conclusion, the present study demonstrated that PDGF was able to activate the GIT1PLCγ1mediated ERK1/2 pathway to control chondrocyte proliferation.