The role of microRNAs in osteoclasts and osteoporosis

Abstract

Osteoclasts are the exclusive cells of bone resorption. Abnormally activating osteoclasts can lead to low bone mineral density, which will cause osteopenia, osteoporosis, and other bone disorders. To date, the mechanism of how osteoclast precursors differentiate into mature osteoclasts remains elusive. MicroRNAs (miRNAs) are novel regulatory factors that play an important role in numerous cellular processes, including cell differentiation and apoptosis, by post-transcriptional regulation of genes. Recently, a number of studies have revealed that miRNAs participate in bone homeostasis, including osteoclastic bone resorption, which sheds light on the mechanisms underlying osteoclast differentiation. In this review, we highlight the miRNAs involved in regulating osteoclast differentiation and bone resorption, and their roles in osteoporosis.

Keywords: 3’ untranslated region; 3’-UTR; ALP, alkaline phosphatase; BMMs, bone marrow macrophages; CBL, Casitas B-lineage lymphoma proto-oncogene; CXCL11, chemokine (C-X-C motif) ligand 11; CXCR3, chemokine (C-X-C motif) receptor 3; Calcr, calcitonin receptor; FasL, Fas ligand; Fzd3, frizzled 3; GM-CSF, Granulocyte macrophage colony-stimulating factor; ITGA5, integrin α5; M-RIP, myosin phosphatase-Rho interacting protein; MAFB, V-maf musculoaponeurotic fibrosarcoma oncogene homolog B; MiRNA, microRNA; MicroRNA; OVX, ovariectomy; PAG1, phosphoprotein associated with glycosphingolipid microdomains; PDCD4, programmed cell death 4; PIO, particle-induced osteolysis; RDX, radixin; SLC39A1, solute carrier family (zinc transporter) member 1; TOB2, transducer of ERBB2; TRAF6, TNF receptor-associated factor 6; TRAP, tartrate-resistant acid phosphatase; osteoclast; osteoporosis; sICAM1, soluble intracellular adhesion molecule.

Figure 1.

Schematic regulatory networks of miRNAs regulating osteoclast differentiation. MiRNAs can directly (solid lines) or indirectly (dotted lines) repress transcriptional factors, and affect osteoclast differentiation, apoptosis, or phenotype. Bold dotted lines indicate the promotion of cellular processes, dotted boxes indicate osteoclast specific genes, and dotted ovals indicate cellular processes or phenotypes.