IL-17 promotes osteoblast differentiation, bone regeneration, and remodeling in mice

Abstract

Bone homeostasis is maintained by concerted actions of bone-forming osteoblasts and bone-resorbing osteoclasts. A wide range of evidence indicates that a proinflammatory cytokine IL-17 promotes osteoclastogenesis. However, the role of IL-17 in osteoblasts is less well-understood. In the current study, the effect of IL-17 on osteogenic differentiation was investigated in mouse calvarial cells. IL-17 stimulated osteoblast differentiation, mineralization, proliferation, motility, and osteoblast-dependent osteoclastogenesis in vitro. The pro-osteogenic role of IL-17 was dependent on Act1 and the generation of reactive oxygen species. In a critical size calvarial defect model, IL-17 significantly augmented bone regeneration. Importantly, IL-17 also remarkably increased bone remodeling and restored osteoclastogenesis in zoledronate-treated mice. Furthermore, IL-17 conspicuously stimulated the formation of lamellar bones. These data not only provide a clue to understand the role of IL-17 in bone metabolism but also suggest possible applications in bone augmentation therapies.

Keywords: Bone regeneration; Bone remodeling; Differentiation; IL-17; Osteoblast.