miR-193-3p ameliorates bone resorption in ovariectomized mice by blocking NFATc1 signaling

Background: Nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) as a key transcription factor contributes to osteoclast differentiation and bone resorption. However, the post-transcriptional mechanisms of microRNAs (miRNAs) targeted to NFATc1 have not been completely clarified in postmenopausal osteoporosis (PMO). In our study, we aimed to investigate the role of miR-193-3p in ovariectomy (OVX)-induced bone loss by regulating the NFATc1 pathway. Methods: Female C57BL/6J mice underwent sham or OVX operation. Injection of Agomir-Control or Agomir-miR-193-3p was performed in OVX mice. Serum, urine and tibia were collected for experimental measurements, including biochemical markers, RT-qPCR and western blotting assays. Results: We identified NFATc1 as a direct target of miR-193-3p. Up-regulation of NFATc1 and down-regulation of miR-193-3p were found in the tibia of OVX mice. Gain-of-function of miR-193-3p resulted in the reduction of NFATc1 mRNA and protein expression in vivo and in vitro. Furthermore, injection of Agomir-miR-193-3p markedly ameliorated OVX-induced Ca2+ dyshomeostasis and bone loss by inhibiting the expression of NFATc1 and its downstream targets of osteoclast-specific genes, Ctsk, TRAP and Car2. Conclusion: Overexpression of miR-193-3p had an osteoprotective effect in OVX mice by suppressing NFATc1 pathways.