Interleukin-6 signaling in osteoblasts regulates bone remodeling during exercise

Aerobic exercise has many beneficial effects on human health. One of them, is to influence positively bone remodeling through, however, incompletely understood mechanisms. Given its recently demonstrated role as a mediator of the bone to muscle to bone crosstalk during exercise, we hypothesized that interleukin-6 (IL-6) signaling in bone may contribute to the beneficial effect that exercise has on bone homeostasis. In this study, we first show that aerobic exercise increases the expression of Il6r in bones of WT mice. Then, we analyzed a mutant mouse strain that lacks the IL-6 receptor alpha specifically in osteoblasts (Il6r_osb^-/-). As it has been reported in the case of Il6^-/- mice, in sedentary conditions, bone mass and remodeling were normal in adult Il6r_osb^-/- mice when compared to controls. In contrast, Il6r_osb^-/- mice that were subjected to aerobic exercise did not show the increase in bone mass and remodeling parameters that control littermates demonstrated. Moreover, Il6r_osb^-/- mice undergoing aerobic exercise showed a severe impairment in bone formation, indicating that activation of bone-forming cells is defective when IL-6 signaling in osteoblasts is disrupted. In sum, this study provides evidence that a function of IL-6 signaling in osteoblasts is to promote high bone turnover during aerobic exercise.