IL-17 inhibits osteoblast differentiation and bone regeneration in rat

Objective: The interleukin-17 (IL-17) family is a group of pro-inflammatory cytokines that are produced by a subset of helper T cells. IL-17 family members are not only involved in the immune response of tissues but also play a role in bone metabolism. Although the role of IL-17 in osteoclast-mediated bone resorption has been extensively studied, its role during osteoblast-mediated bone formation has rarely been investigated. In this study, we examined the effect of IL-17 on osteogenesis in rats both in vitro and in vivo. Design: To evaluate osteogenesis in vitro, rat calvarial osteoblast precursor cells were cultured for 14 days in osteogenic medium with or without 50 ng/mL IL-17. Osteogenic activity was evaluated by alkaline phosphatase and alizarin red staining. The mRNA expression of alkaline phosphatase, osteocalcin, and osterix was also measured by using real-time PCR. To test whether IL-17 affects bone formation in vivo, bone filling was examined by micro-computed tomography and histological observations at 8 weeks after critical-sized defects were made in rat calvaria. Results: The presence of IL-17 significantly reduced alkaline phosphatase and alizarin red staining and the expression of alkaline phosphatase, osteocalcin, and osterix in vitro. IL-17 also significantly inhibited the filling of calvarial defects in vivo. Conclusion: IL-17 exerted a negative effect on osteogenesis in a rat model. In contrast to the previously reported beneficial effect on osteogenic differentiation of human mesenchymal stem cells, our results suggest a species or cell type-specific role for IL-17 in bone formation. (C) 2014 Elsevier Ltd. All rights reserved.