IL-17F promotes osteoblastic osteogenesis via the MAPK/ERK1/2 signaling pathway

Osteoimmunology is a field that focuses on the interactions between the skeletal and immune systems, and has become a focus of research over the years. The role of interleukin (IL)-17F, a proinflammatory cytokine, in bone regeneration and its signal transduction are not completely understood. The aim of the present study was to evaluate the function of IL-17F and the possible mechanisms underlying IL-17F in osteoblasts in vitro. Osteoblasts derived from newborn rats were treated with various concentrations of IL-17F. The pro-osteogenic effects of IL-17F were assessed at the cellular and molecular level. The results demonstrated that IL-17F promoted osteoblast proliferation, differentiation and mineralization. Reverse transcription-quantitative PCR and western blotting indicated that IL-17F treatment upregulated osteogenesis-related factors, including bone morphogenetic protein-2, Runt-related transcription factor-2 (Runx2) and Osterix, and downregulated Noggin compared with the control group. Subsequently, whether the IL-17F receptors, IL-17 Receptor (IL-17R) A and IL-17RC, served a role in the effects of IL-17F on osteoblasts was investigated. The mRNA expression levels of IL-17RA and IL-17RC were upregulated in IL-17F-treated osteoblasts compared with control osteoblasts. Furthermore, U0126, a MAPK/ERK1/2 inhibitor, was utilized to investigate the mechanisms underlying IL-17F. The results indicated that compared with the control group, IL-17F increased the protein expression of phosphorylated-ERK1/2, Runx2 and Osterix, whereas U0126 reversed IL-17F-mediated effects. Collectively, the results of the present study suggested that IL-17F promoted osteoblastic osteogenesis via the MAPK/ERK1/2-mediated signaling pathway. IL-17F promoted osteogenesis, including proliferation, differentiation and mineralization activity, indicating that IL-17F may serve as a potential therapeutic target for osteoblast-mediated bone loss disease.

ERK1/2; MAPK; interleukin-17F; interleukin-17F receptor; osteoblast; osteogenesis.