Dendritic cells differentiate into osteoclasts in bone marrow microenvironment in vivo

摘要

We read the recent article by Wakkach et al regarding differentiation of murine dendritic cells (DCs) into osteoclasts (OCs) in bone marrow (BM) microenvironment in vivo, with different views to stimulate clarification before any conclusions may be drawn.The authors report that CD11c~+ dendritic cells (cDCs) with "100% purity," carrying a "mature" phenotype of MHC-II~+CD80~+/CD86~+, can differentiate into OCs in vitro and in vivo. Caution should be exercised as potential contaminating OC precursors (OCPs) may alter the observed results, whereas the exclusion of Ly-6C and F4/80 expressions on cDCs is not sufficient to completely eliminate monocyte/macrophagecontaminants that may contribute to the rescued phenotype observed (ie, CD11c~+ monocytes reported). We and others showed that only "immature" cDCs (MHC-II~(lo)CD80~-CD86~-) carry osteoclastogenicpotential and that upon maturation this potential is lost even if receptor activator NFKB ligand (RANKL) was provided thereafter.In our studies, both splenic and BM-derived CD11c~+ DCs act as OCPs based on phenotypic and functional analyses in vitro/in vivo. Wakkach et al report that cDC maturation via activation of Toll-like receptors does not alter their osteoclastogenic potential, where no evidence is provided nor discussed based on previous opposite reports. Splenic DCs were known to become apoptotic in less than 3 days upon maturation in vitro/in vivo, whereas the authors detected TRAP~+ multinucleated OCs after 7 days' culture of mature cDCs, requiring explanation. Whether macrophage-colony stimulating factor (M-CSF) can rescue such osteoclastogenic potential of mature DCs as described becomes another issue, yet to be further addressed.