Interferon- and - differentially regulate osteoclastogenesis: Role of differential induction of chemokine CXCL11 expression

In humans, type I interferon (IFN) is a family of 17 cytokines, among which the subtypes and the subtype are differentially expressed. It has been suggested that IFNactivates a specific signaling cascade in addition to those activated by all type I IFNs. Nevertheless, no true biological relevance for a differential activity of and IFN subtypes has been identified so far. Because type I IFNs are critical for the regulation of osteoclastogenesis in mice, we have compared the effect of IFN2 and IFNon the differentiation of human monocytes into osteoclasts. Primary monocytes undergoing osteoclastic differentiation are highly and equally sensitive to both 2 and IFNs as determined by measuring the induction levels of several IFN-stimulated genes. However, IFNwas 100-fold more potent than the 2 subtype at inhibiting osteoclastogenesis. Expression profiling of the genes differentially regulated by IFN2 and IFNin this cellular system revealed the chemokine CXCL11 as the only IFN-induced gene differentially up-regulated by IFN. We show that recombinant CXCL11 by itself inhibits osteoclastic differentiation. These results indicate that autocrine-acting CXCL11 mediates, at least in part, the regulations of osteoclastogenesis by type I IFNs.