CXCL2 mediates lipopolysaccharide-induced osteoclastogenesis in RANKL-primed precursors.

The strong inflammatory agent lipopolysaccharide (LPS) has been shown to cause bone lysis in vivo. However, the etiology of LPS-induced bone destruction is still elusive. Here, we show that LPS stimulates the induction of CXCL2 in bone marrow macrophages (BMMs), osteoclast precursors, at the transcription level even in the absence of the synthesis of new proteins including interferon β. Reactive oxygen species were involved in the secretion of CXCL2 but not in the mRNA expression. CXCL2 mRNA induction by LPS was mediated by p38, JNK, and NFκB signaling pathways. Moreover, c-Fos and p65 were directly recruited to CXCL2 promoter. The conditioned medium from LPS-treated BMMs could enhance migration of osteoclast precursors, which was blocked by treatment with CXCL2-neutralizing antibody or CXCR2 receptor antagonist. The blockade of CXCL2 also reduced LPS-induced osteoclastogenesis. More significantly, CXCL2-neutralization prevented bone destruction in mice treated with LPS. Therefore, CXCL2 might be a useful therapeutic target for inflammatory bone destructive diseases.