The role of MicroRNAs in Osteoclasts and Osteoporosis

Abstract

These authors contributed equally to this work. Keywords: MicroRNA, osteoclast, osteoporosisAbbreviations: GM-CSF, Granulocyte macrophage colony-stimulating factor; MiRNA, microRNA; 3'-UTR; 3' untranslated region; BMMs, bone marrow macrophages; PDCD4, programmed cell death 4; FasL, Fas ligand; PIO, particle-induced osteolysis; Calcr, calcitonin receptor; RDX, radixin; M-RIP, myosin phosphatase-Rho interacting protein; ITGA5, integrin a5; Fzd3, frizzled 3; ALP, alkaline phosphatase; TRAP, tartrate-resistant acid phosphatase; CXCL11, chemokine (C-X-C motif) ligand 11; CXCR3, chemokine (C-X-C motif) receptor 3; SLC39A1, solute carrier family (zinc transporter) member 1; TRAF6, TNF receptor-associated factor 6; OVX, ovariectomy; MAFB, V-maf musculoaponeurotic fibrosarcoma oncogene homolog B; CBL, Casitas B-lineage lymphoma proto-oncogene; PAG1, phosphoprotein associated with glycosphingolipid microdomains; TOB2, transducer of ERBB2; sICAM1, soluble intracellular adhesion molecule.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.

Serum miRNA Signatures Are Indicative of Skeletal Fractures in Postmenopausal Women With and Without Type 2 Diabetes and Influence Osteogenic and Adipogenic Differentiation of Adipose Tissue–Derived Mesenchymal Stem Cells In Vitro

“…(64) Other miRNAs, such as miR-21 and miR-378, have been implicated in osteoclastogenesis. (65) In particular, miR-21 is of interest because miR-21 is not only known as "inflamma-miR," (66) but has been shown to mediate RANKL-induced osteoclast differentiation (67) and inhibit osteoclast apoptosis. (68) Given that we found significantly higher serum miR-21 serum levels in DMFx than in DM subjects and that DMFx were described to have more cortical porosity, (29) osteoclast dysfunction/or prolonged osteoclast survival might be a potential mechanisms that could explain the higher fracture risk in the DMFx patients.…”

MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting

“…A recent study confirmed that Dex acts on osteoblasts to up-regulate the expression of RANKL, which indirectly affects osteoclast differentiation and bone resorption (Shi et al, 2014). Furthermore, accumulating evidence demonstrates that miRNAs are involved in RANKL-induced osteoporosis (Tang et al, 2014). In the current study, we demonstrated that the inhibitory effect of miR-338-3p on osteoclast differentiation and bone resorption could be reversed by exogenous RANKL treatment, suggesting that miR-338-3p inhibited GC-induced osteoporosis by targeting RANKL expression.…”

“…miRNAs have been implicated in various pathophysiological events including embryogenesis, organogenesis, differentiation, metabolism, proliferation, and apoptosis (Couzin, 2007). Recent research on osteoclasts has focused on miRNAs as they have been shown to play crucial roles in their differentiation and function, indicating that miRNAs are novel regulatory factors of osteoclastogenesis (Tang et al, 2014). Therefore, miRNAs may represent new therapeutic targets for the pharmacological control of bone diseases.…”

Pygmy MicroRNA: Surveillance Cops in Therapy Kingdom

“…miRNAs such as miR-223, miR-103a, and miR-140 have been reported to regulate bone metabolism by modulating bone formation, reabsorption, and osteoblast-osteoclast activity (140,141). miRNA expression profiling data in osteoporosis and osteoporotic fracture patients have clearly described that miRNAs play a crucial role in bone metabolism.…”