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miR-193-3p ameliorates bone resorption in ovariectomized mice by blocking NFATc1 signaling
Xiuhua Li1, Limin Yang1, Zhanpeng Guo1
1Department of Orthopedics, The First Affiliated Hospital of Jinzhou Medical University Jinzhou 121001, Liaoning Province, China.
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.
Insights
MicroRNA-193-3p (miR-193-3p) protects against bone loss in postmenopausal osteoporosis (PMO) by targeting Nuclear Factor of activated T cells, cytoplasmic 1 (NFATc1). This study reveals miR-193-3p as a potential therapeutic target for PMO.
Area of Science:
- Molecular Biology
- Endocrinology
- Bone Biology
Background:
- Nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) is crucial for osteoclast differentiation and bone resorption.
- Post-transcriptional regulation of NFATc1 by microRNAs (miRNAs) in postmenopausal osteoporosis (PMO) remains incompletely understood.
Purpose of the Study:
- To investigate the role of miR-193-3p in regulating the NFATc1 pathway in ovariectomy (OVX)-induced bone loss.
- To determine if miR-193-3p has a therapeutic effect on PMO.
Main Methods:
- Ovariectomy (OVX) model in C57BL/6J mice.
- Administration of Agomir-miR-193-3p to OVX mice.
- Analysis of serum, urine, and tibia using biochemical markers, RT-qPCR, and western blotting.
Main Results:
- NFATc1 was identified as a direct target of miR-193-3p.
- OVX mice showed increased NFATc1 and decreased miR-193-3p in tibia.
- miR-193-3p overexpression reduced NFATc1 expression and ameliorated OVX-induced bone loss and calcium dyshomeostasis.
Conclusions:
- Overexpression of miR-193-3p exerts an osteoprotective effect in OVX-induced osteoporosis.
- Suppression of the NFATc1 pathway by miR-193-3p is the underlying mechanism for its therapeutic benefit.
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