Bone Abstracts

Existence of inflammatory osteoclasts (iOCLs) contributing to pathological bone resorption associated with inflammatory diseases has been suspected for many years. However, specific markers of iOCLs are lacking, making impossible to establish the contribution of iOCLs to such pathologies. Whereas in steady state OCLs derive from monocytes (MN-OCLs), in inflammatory conditions, they also differentiate from dendritic cells (DC-OCLs). We recently showed that these 2 OCL populations are antigen-presenting cells that drive different CD4+ T cells responses in vitro. MN-OCLs induce the differentiation of CD4+ T cells into regulatory T (Treg) cells and DC-OCLs induce their differentiation into TNFα-producing cells. These differences were confirmed with OCLs generated from normal or inflamed mice using a murine model of inflammatory bowel disease (IBD) associated with severe bone destruction, the Rag1^−/− mice transferred with naive CD4+ T cells. Contrasting with OCLs from control mice that induce CD4+ Treg cells as MN-OCLs, OCLs from IBD mice have inflammatory properties similar to DC-OCLs. Taking advantage of these different tolerogenic or inflammatory OCL populations, our aim was to identify cell surface markers to characterize iOCLs subsets. We have performed a comparative flow cytometry analysis of DC-OCLs and MN-OCLs on about 20 surface markers described for monocytes and dendritic cells. We have observed that expression of CX3CR1, the receptor of fractalkine, is restricted to DC-OCLs. Using the IBD model, we have confirmed that CX3CR1+OCLs are characteristic of IBD development. Moreover, these CX3CR1+OCLs induce inflammatory CD4+ T cells but not Treg cells. Lastly, we have shown that the emergence of CX3CR1+ OCLs is controlled by IL17. These results are the first characterization of a marker allowing the identification of iOCLs. They provide also an essential tool for the study, diagnosis and therapeutic targeting of i-OCLs.