PDGF-BB promotes the differentiation and proliferation of MC3T3-E1 cells through the Src/JAK2 signaling pathway

Abstract

Platelet-derived growth factor-BB (PDGF-BB) serves a critical function in human osteoblast differentiation and proliferation. Src and Janus kinase 2 (JAK2) are involved in these processes. In our previous study, it was identified that Src could promote the phosphorylation of JAK2. However, it has yet to be determined whether the Src/JAK2 signaling pathway affects PDGF-BB-mediated osteoblast differentiation and proliferation. In the present study, western blotting, polymerase chain reaction, alizarin red staining, alkaline phosphatase and Cell Counting kit-8 were employed to explore these questions. Firstly, it was demonstrated that PDGF-BB activates the Src/JAK2 signaling pathway in MC3T3-E1 cells in a time-dependent manner. Furthermore, it was demonstrated that PDGF-BB expression promoted MC3T3-E1 cell differentiation and proliferation; this process was suppressed by AG1295, SU6656 and AG490, which are inhibitors of PDGFR-β, Src and JAK2, respectively. SU6656 downregulated the activity of Src and JAK2, while AG490 only downregulated JAK2 activity. Therefore, it was concluded that Src is upstream of JAK2. PDGF-BB also upregulated the expression of osteogenesis-associated genes, and the formation of mineral nodules. However, these effects were markedly inhibited by treatment with SU6656. This indicated that PDGF-BB promoted MC3T3-E1 cell differentiation and proliferation by activating the Src/JAK2 signaling pathway. These results suggested that PDGF-BB may have potential applications in the treatment of osteoporosis and bone fractures.