Genome-wide expression analyses establish dendritic cells as a new osteoclast precursor able to generate bone-resorbing cells more efficiently than monocytes

Abstract

Dendritic cells (DCs), mononuclear cells that initiate immune responses, and osteoclasts (OCs), multinucleated bone-resorbing cells, are hematopoietic cells derived from monocytic precursor cells. Using in vitro generated dendritic cells, we previously showed that human and murine DCs could transdifferentiate into resorbing osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL). In this study we globally compared by transcriptomic profiling this new osteoclast differentiation pathway from DCs with the canonical differentiation pathway from monocytes. DNA chip data revealed that starting from two very distinct cell types, treatment with M-CSF and RANKL generated two highly similar types of osteoclast. In particular, DC-derived osteoclasts expressed all the characteristic marker genes of monocyte-derived osteoclasts. Two major molecular events could be observed during osteoclastogenesis: downregulation of a large set of monocyte or DC specific markers, together with upregulation of characteristic osteoclast marker genes. Most interestingly, our transcriptomic data showed a closer molecular profile between DCs and OCs than between monocytes and OCs. Our data establish DCs as a new osteoclast precursor able to generate OCs more efficiently than monocytes. ß

Exploring Codon Optimization and Response Surface Methodology to Express Biologically Active Transmembrane RANKL in E. coli

“…Osteoclasts express several markers, such as TRAP, CALCR and CFMS throughout the differentiation process which, along with multinucleation and resorption, characterize the osteoclast phenotype [47]. CALCR is expressed on the surface of mature osteoclast and it has been described as the best differentiation marker for the osteoclast [48].…”

PU.1 target genes undergo Tet2-coupled demethylation and DNMT3b-mediated methylation in monocyte-to-osteoclast differentiation

“…We used osteoclastogenesis expression data (available from the ArrayExpress database under accession number E-MEXP-2019) on 0, 5, and 20 days [32]. Our analysis showed that most changes occurred within the first 5 days, since the expression changes between 0 and 5 days were very similar to those observed between 0 and 20 days, and very few genes changed between 5 and 20 days (Figure 2A and Additional file 6).…”

Podosome organization drives osteoclast-mediated bone resorption

“…Strikingly, all the data so far obtained have described wide osteoclastogenic plasticity across the myeloid lineage of which very early myeloid precursors as well as committed Mo, macrophages, and DCs can differentiate into OCs. [11][12][13][14][15][16][17] It is now established that M-CSF induces GMPs or GMPderived cells to differentiate into OCs precursors that express RANK, the receptor of RANKL, and Triggering receptor expressed by myeloid cells-2 (TREM2). 18,19 Upon recognition of RANKL by RANK and activation of Immunoreceptor tyrosinebased activation motif (ITAM) family receptors, OC precursors undergo further differentiation to mononuclear pre-OCs with a high activity of the transcription factor Nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and a high expression of resorption-related genes, e.g.…”