Wheel-Running Exercise Protects Ovariectomized Mice from Bone Loss via IFN-γ-Mediated Suppression of the NF-κB and MAPK Pathways

Figure 9

Summary of the proposed mechanism responsible for the recovered bone loss of OVX mice after WR exercise. In OVX mice, WR exercise activates CD8⁺ T cells to produce the inflammatory cytokine IFN-γ, which inhibits osteoclastogenesis and bone resorption through the NF-κB and MAPK signaling pathways. The suppression of IκB and p65 phosphorylation in the NF-κB pathway, as well as the suppression of ERK and p38 phosphorylation in the MAPK pathway, triggers a decreased level of NFATc1. As a result, the expression of osteoclast marker genes is downregulated.