Functional role of endogenous CD14 in lipopolysaccharide-stimulated bone resorption.

Lipopolysaccharide (LPS) is a bacterial cell component that plays multifunctional roles in inflammatory reactions, and one of these roles is that of a powerful stimulator of bone resorption. However, the mechanism by which LPS stimulates bone resorption is not yet understood. In the present study, we show, by using mouse embryonic calvarial cells, that endogenous CD14 and interleukin-1β (IL-1β) play an important role in the LPS-mediated bone resorption and that interferon-γ (IFN-γ)functions as a strong inhibitor of this resorption by suppressing LPS-stimulated expression of CD14 and IL-1β genes in the calvarial cells. We observed that LPS-stimulated differentiation of osteoclastic cells and bone and resorption were markedly neutralized by anti-mouse CD14 antibody were clearly inhibited by anti-sense CD14 oligonucleotide treatment. In addition, because LPS stimulated CD14 gene expression in the calvarial cells, these observations demonstrate the precise role of endogenous CD14 in LPS-stimulated differentiation of osteoclastic cells and boneresorption. However, the stimulation of the differentiation of osteoclastic cells and bone resorption was also inhibited by anti-mouse IL-1β antibody. Interestingly, anti-sense CD14 oligonucleotide inhibited LPS-stimulated expression of the IL-1β gene in the calvarial cells. These observations suggest a functional role of endogenous CD14 in LPS-stimulated expression of the IL-1β gene in the cells. Because IFN-γ is a potent inhibitor of bone resorption stimulated by IL-1, in additional experiments, we examined whether IFN-γ is able to inhibit LPS-stimulated differentiation of osteoclastic cells and bone resorption. We found that IFN-γ inhibited these stimulations by suppressing CD14 and IL-1β genes in the calvarial cells. The present study thus clearly demonstrates a functional role of endogenous CD14 in LPS-stimulated bone resorption. J. Cell. Physiol. 173:301–309, 1997. © 1997 Wiley-Liss, Inc.