Interleukin‐37 inhibits osteoclastogenesis and alleviates inflammatory bone destruction

Excessive osteoclast formation is one of the important pathological features of inflammatory bone destruction. Interleukin‐37 (IL‐37) is an anti‐inflammatory agent that is present throughout the body, but it displays low physiological retention. In our study, high levels of the IL‐37 protein were detected in clinical specimens from patients with bone infections. However, the impact of IL‐37 on osteoclast formation remains unclear. Next, IL‐37 alleviated the inflammatory bone destruction in the mouse in vivo. We used receptor activator of nuclear factor‐κB ligand and lipopolysaccharide to trigger osteoclastogenesis under physiological and pathological conditions to observe the role of IL‐37 in this process and explore the potential mechanism of this phenomenon. In both induction models, IL‐37 exerted inhibitory effects on osteoclast differentiation and bone resorption. Furthermore, IL‐37 decreased the phosphorylation of inhibitor of κBα and p65 and the expression of nuclear factor of activated T cells c1, while the dimerization inhibitor of myeloid differentiation factor 88 reversed the effects. These data provide evidence that IL‐37 modulates osteoclastogenesis and a theoretical basis for the clinical application of IL‐37 as a treatment for bone loss–related diseases.