MiR-142-3p is a RANKL-dependent inducer of cell death in osteoclasts.
MicroRNA are small, non-coding, single-stranded RNAs that are estimated to regulate ~60% of the human genome. MiRNA profiling of monocyte-to-osteoclast differentiation identified miR-142-3p as a miRNA that is significantly, differentially expressed throughout osteoclastogenesis. Enforced expression of miR-142-3p via transient transfection with miR-142-3p mimic inhibited cell-to-cell contact and fusion, decreased protein kinase C alpha expression, and ultimately reduced cell viability. miR-142-3p was also identified as significantly differentially expressed during monocyte-to-macrophage differentiation and overexpression of miR-142-3p prevented their conversion to osteoclasts. Furthermore, the inhibitory effect of miR-142-3p on osteoclastogenesis extended to the conversion of a third osteoclast precursor cell type- dendritic cells. These results demonstrate miR-142-3p to be a negative regulator of osteoclastogenesis from the 3 main precursor cell types: monocytes, macrophages and dendritic cells. Importantly, decreased survival was dependent upon both miR-142-3p expression and RANK-signaling, with no harmful effects detected in the absence of this combination. As such, miR-142-3p represents a novel target for the selective removal of osteoclasts by targeting of osteoclastogenic pathways.
Department of Periodontics, University of Illinois at Chicago, Chicago, Illinois, USA.
Jezrom B
JB
Fordham
University of North Carolina at Chapel Hill, School of Dentistry, Department of Periodontics, 385 S. Columbia St., Chapel Hill, NC, 27599, USA.
Katherine
K
Guilfoyle
Department of Periodontics, University of Illinois at Chicago, Chicago, Illinois, USA.
Afsar Raza
AR
Naqvi
Department of Periodontics, University of Illinois at Chicago, Chicago, Illinois, USA.
Salvador
S
Nares
D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D010012:Osteogenesis; D051571:Protein Kinase C-alpha / Q000235:genetics*; D053245:RANK Ligand / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
C555159:MIRN142 microRNA, human; D035683:MicroRNAs; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha