Distinct cross talk of IL-17 & TGF-β with the immature CD11c TRAF6 -null myeloid dendritic cell-derived osteoclast precursor (mDDOCp) may engage signaling toward an alternative pathway of osteoclastogenesis for arthritic bone loss in vivo.

BACKGROUND

Dendritic cells (DCs), though borne heterogeneous, are the most potent antigen-presenting cells, whose critical functions include triggering antigen-specific naïve T-cell responses and fine-tuning the innate versus adaptive immunity at the osteo-immune and/or mucosal mesenchyme interface. We previously reported that immature myeloid-CD11c DCs/mDCs may act like osteoclast (OC) precursors (OCp/mDDOCp) capable of developing into functional OCs via an alternative pathway of inflammation-induced osteoclastogenesis; however, what are their contribution and signaling interactions with key osteotropic cytokines (i.e., interleukin-17 [IL-17] and transforming growth factor-β [TGF-β]) to bearing such inflammatory bone loss in vivo remain unclear to date.

METHODS

Herein, we employed mature adult bone marrow-reconstituted C57BL/6 TRAF6 -null chimeras without the classical monocyte/macrophage (Mo/Mϕ)-derived OCs to address their potential contribution to OCp/mDDOCp-mediated osteoclastogenesis in the chicken type-II-collagen (CC-II)-induced joint inflammation versus arthritic bone loss and parallel associations with the double-positive CD11c TRAP TRAF6-null  DC-like OCs detected in vivo via the quantitative dual-immunohistochemistry and digital histomorphometry for analyses.

RESULTS

The resulting findings revealed the unrecognized novel insight that (i) immature myeloid-CD11c TRAF6 TRAP DC-like OCs were involved, co-localized, and strongly associated with joint inflammation and bone loss, independent of the Mo/Mϕ-derived classical OCs, in CC-II-immunized TRAF6 -null chimeras, and (ii) the osteotropic IL-17 may engage distinct crosstalk with CD11c mDCs/mDDOCp before developing the CD11c TRAP TRAF6 OCs via a TGF-β-dependent interaction toward inflammation-induced arthritic bone loss in vivo.

CONCLUSION

These results confirm and substantiate the validity of TRAF6 -null chimeras to address the significance of immature mCD11c TRAP DC-like OCs/mDDOCp subset for an alternative pathway of arthritic bone loss in vivo. Such CD11c mDCs/mDDOCp-associated osteoclastogenesis through the step-wise twist-in-turns osteo-immune cross talks are thereby theme highlighted to depict a summative re-visitation proposed.