Platelet-derived growth factor promotes osteoblast proliferation by activating G-protein-coupled receptor kinase interactor-1

Abstract

Platelet-derived growth factor (PDGF) has been reported to stimulate bone fracture-healing. Multiple studies have demonstrated that PDGF has a critical role in osteoblast or osteoprogenitor cell activation, although the underlying mechanism remains unclear. Studies have found that G-protein-coupled receptor kinase interactor-1 (GIT1) is activated by PDGF and described as an important factor in bone metabolism. In the present study, the effects of PDGF and GIT1 on the proliferation and apoptosis of osteoblasts were investigated in cultured osteoblasts isolated from rat calvaria with PDGF stimulation and GIT1 small interfering RNA transfection. The results demonstrated that PDGF rapidly stimulated GTI1 expression in osteoblasts, increased osteoblast proliferation and inhibited cell apoptosis. Furthermore, cyclin D1 expression was significantly upregulated, the number of cells in the G0/G1 phase was decreased, while the number in the S phase was increased. In cells with knockdown of GIT1, the change stimulated by PDGF was not evident. The results indicate that, PDGF stimulated GIT1 activation of cyclin D1 expression, thereby promoting osteoblasts to enter the S phase from the stationary G0/G1 phase, leading to the proliferation of osteoblasts.