Achievements

Osteoclasts (OC) form by fusion of heterogeneous OC precursors (OCP). As OCP heterogeneity can be phenotyped by fusogenic potential (multinucleated master fusogens vs. mononuclear OCP donors) we hypothesized that DC-STAMP, a 7-transmembrane protein receptor required for OCP fusion, mediates this heterogeneity. To test this we evaluated the expression of fusogenic genes and the fusogenic potential of DC-STAMPhi vs. DC-STAMPlo OCP after culture with RANKL. We also evaluated DC-STAMP as an OCP biomarker in patients with inflammatory-erosive psoriatic arthritis (PsA). Although the DC-STAMP ligand remains unknown, this RANKL-induced factor delivers a critical signal to DC-STAMPhi mononuclear OCP, which induces the expression of genes involved in cell fusion while down-regulating DC-STAMP surface expression. The resulting DC-STAMPlo OCP are “master fusogens” that express higher levels of OC markers and pseudopods that seek out and attach to DC-STAMPhi OCP to form multinucleated OC. The higher frequency of DC-STAMP+ cells among PsA patients versus healthy controls suggests that DC-STAMP surface expression on PBMC, prior to RANKL exposure, may be a dynamic biomarker to assess the aggressiveness of erosive arthritis.