IL-10 inhibits osteoclast differentiation and osteolysis through MEG3/IRF8 pathway

Osteolysis caused by wear particles is the main reason for joint replacement failure. Inhibition of osteoclast differentiation relieves wear particle-induced osteolysis. Our study aimed to explore the effect of lncRNA maternally expressed gene 3 (MEG3) on osteoclast differentiation and wear particle-induced osteolysis, and to improve the potential mechanism of interleukin-10 (IL-10) inhibition on osteoclast differentiation. Polymethylmethacrylate (PMMA) -induced osteolysis mice model and receptor activator of nuclear factor-B ligand (RANKL) -induced osteoclast differentiation model were constructed. Tartrate-resistant acidic phosphatase (TRAP) staining, hematoxylin-eosin (HE) staining, immunohistochemical staining, bone resorption assay, dual-luciferase assay, RNA pull-down assay, RNA immunoprecipitation, and chromatin immunoprecipitation were executed. MEG3 levels were increased and interferon regulatory factor 8 (IRF8) levels were decreased in PMMA-induced osteolysis mice. IL-10 inhibited RANKL-induced osteoclast differentiation, promoted MEG3 methylation, and inhibited MEG3 expression. Moreover, knockdown of MEG3 inhibited osteoclast differentiation and increased IRF8 levels. Meanwhile, MEG3 combined with signal transducer and activator of transcription 1 (STAT1), STAT1 combined with IRF8, and overexpression of MEG3 inhibited STAT1 binding to IRF8. Further studies have shown that knockdown of MEG3 inhibited osteoclast differentiation and alleviated osteolysis, but knockdown of IRF8 weakened these results. MEG3 regulated the expression of IRF8 by binding to STAT1, thereby affecting osteoclast differentiation and wear particle-induced osteolysis. IL-10 might inhibit osteoclast differentiation by MEG3/IRF8. •MEG3 is involved in osteoclast differentiation and osteolysis.•The knockdown of MEG3 inhibited the differentiation of macrophages into osteoclasts.•MEG3 could bind with STAT1 to regulate the expression of IRF8•IL-10 inhibited osteoclast differentiation by MEG3/IRF8 axis