Potential contribution of immature myeloid CD11cdendritic cells-derived osteoclast precursor to inflammation-induced bone loss in the TRAF6-null chimeras .

Dendritic cells (DC) are potent antigen-presenting-cells widely distributed at the osteo-immune and/or mucosal-mesenchyme interface, consequentially implicating in certain bone-sparing disorders; i.e., via signaling Receptor-activator-of-nuclear-factor-kappa-B-ligand/RANKL-Receptor-activator-of-nuclear-factor-kB/RANK-Osteoprotegerin/OPG-TRAF6 transducer-complex , evidently associated with arthritis, osteoporosis and periodontitis. We have reported that the immature myeloid CD11c-DC subsets can act as osteoclast precursor (OCp; mDDOCp), thereby developing into osteoclasts (OCs) via an alternative pathway for osteoclastogenesis. Importantly, cytokine TGF-β remains critical to prime CD11c-mDDOCp-cells deficient of TRAF6-&-related immune/osteotropic signaling, featuring distinctive TGF-β-&-IL-17-invoked effectors in the environmental milieu sufficient to driving bona-fide osteoclastogenesis . Herein, we sought to explore the potential contribution of immature-mDDOCp/OCp to inflammation-induced bone-loss, where comparable CD11cTRAPmultinucleated-OC-like/mDDOCp existed, lacking the endogenous TRAF6-associated monocyte/macrophage-derived OCs in type-II-collagen induced joint/paw inflammation of the C56BL/6-TRAF6null chimeras (H-2-halpotype) examined. The results suggest that such TRAF6-null chimeric mice may offer a useful model to assess the specific functions of OCp or mDDOCp as an analog to human conditions .