RESUMO

The differentiation deficiencies of osteoclast precursors (pre-OCs) may contribute to osteoporosis. Research on osteoporosis has recently focused on microRNAs (miRNAs) that play crucial roles in pre-OC differentiation. In the current study, we aimed to analyze the expression and function of the glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation. We found that dexamethasone induced osteoclast differentiation and inhibited miR-338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor cells attenuated GC-induced osteoclast formation and bone resorption, whereas inhibition of miR-338-3p reversed these effects. The expression of the nuclear factor κB ligand RANKL, a potential target gene of miR-338-3p, was inversely correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone resorption. Taken together, these findings demonstrate that miR-338-3p may play a significant role in GC-induced osteoclast differentiation and function by targeting RANKL in osteoclasts.

Assuntos

Reabsorção Óssea/genética , Dexametasona/farmacologia , Glucocorticoides/farmacologia , MicroRNAs/genética , Osteoclastos/efeitos dos fármacos , Ligante RANK/genética , Animais , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Bovinos , Diferenciação Celular/efeitos dos fármacos , Técnicas de Cocultura , Feminino , Fêmur/efeitos dos fármacos , Fêmur/metabolismo , Fêmur/patologia , Regulação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Modelos Biológicos , Oligorribonucleotídeos Antissenso/genética , Oligorribonucleotídeos Antissenso/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patologia , Cultura Primária de Células , Ligante RANK/metabolismo , Transdução de Sinais