Deletion of IL-17ra in osteoclast precursors increases bone mass by decreasing osteoclast precursor abundance

Metabolic bone diseases, such as osteoporosis, typically reflect an increase in the number and activity of boneresorbing osteoclasts that result in a loss of bone mass. Inflammatory mediators have been identified as drivers of both osteoclast formation and activity. The IL-17 family of inflammatory cytokines has gained attention as important contributors to both bone formation and resorption. The majority of IL-17 cytokines signal through receptor complexes containing IL-17a receptor (IL-17ra); however, the role of IL-17ra signaling in osteoclasts remains elusive. In this study, we conditionally deleted 1117ra in osteoclast precursors using LysM-Cre and evaluated the phenotypes of skeletally mature male and female conditional knockout and control mice. The conditional knockout mice displayed an increase in trabecular bone microarchitecture in both the appendicular and axial skeleton. Assessment of osteoclast formation in vitro revealed that deletion of 1117ra decreased osteoclast number, which was confirmed in vivo using histomorphometry. This phenotype was likely driven by a lower abundance of osteoclast precursors in IL-17ra conditional knockout mice. This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss.

Automated summary

This study suggests that IL-17ra signaling in preosteoclasts can contribute to osteoclast formation and subsequent bone loss. The deletion of IL-17ra in osteoclast precursors may lead to increased trabecular bone microarchitecture and decreased osteoclast number.