Dataset Information

Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis.

ABSTRACT:

Background

Bone homeostasis is a tightly orchestrated process maintained by osteoblasts and osteoclasts, and a disruption of their steady-state equilibrium can lead to the occurrence of osteoporosis (OP).

Methods

We investigated the differential expression of micro (mi)RNAs in the bone tissues of a postmenopausal osteoporosis rat model induced by ovariectomy (OVX). Real-time PCR was used to verify the differentially expressed miRNAs in bone samples from OP patients and controls. The specific targets of two differentially expressed miRNAs in osteogenic or osteoclast differentiation were determined by bioinformatic prediction, and mRNA and protein detection.

Results

miR-708-5p and miR-708-3p were highly expressed in the bone tissue of OVX rats and OP patients. miR-708-5p negatively regulated osteoblast differentiation in bone marrow mesenchymal stem cells by targeting SMAD specific E3 ubiquitin protein ligase 2, while miR-708-3p positively regulated osteoclast differentiation in bone marrow monocytes by targeting cerebellar degeneration associated protein 1 antisense RNA. miR-708-5p and miR-708-3p were shown to originate from the same precursor miRNA and to have a synergistic effect on the development of osteoporosis with different temporal and spatial patterns.

Conclusion

Our findings provide a referential theoretical basis and targets for the prevention and treatment of osteoporosis.

SUBMITTER: Wang R

PROVIDER: S-EPMC7745577 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis.

Wang Ruran R Feng Yanhua Y Xu Huaying H Huang Haoran H Zhao Shan S Wang Yuhong Y Li Hongyan H Cao Jian J Xu Guoying G Huang Shengnan S

The Journal of international medical research 20201201 12

<h4>Background</h4>Bone homeostasis is a tightly orchestrated process maintained by osteoblasts and osteoclasts, and a disruption of their steady-state equilibrium can lead to the occurrence of osteoporosis (OP).<h4>Methods</h4>We investigated the differential expression of micro (mi)RNAs in the bone tissues of a postmenopausal osteoporosis rat model induced by ovariectomy (OVX). Real-time PCR was used to verify the differentially expressed miRNAs in bone samples from OP patients and controls. T ...[more]

PMID: 33322976

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Project description:BACKGROUND:Duchenne (DMD) and Becker (BMD) muscular dystrophies are caused by mutations in the DMD gene coding for dystrophin, a protein being part of a large sarcolemmal protein scaffold that includes the neuronal nitric oxide synthase (nNOS). The nNOS was shown to play critical roles in a variety of muscle functions and alterations of its expression and location in dystrophic muscle fiber leads to an increase of the muscle fatigability. We previously revealed a decrease of nNOS expression in BMD patients all presenting a deletion of exons 45 to 55 in the DMD gene (BMDd45-55), impacting the nNOS binding site of dystrophin. Since several studies showed deregulation of microRNAs (miRNAs) in dystrophinopathies, we focused on miRNAs that could target nNOS in dystrophic context. METHODS:By a screening of 617 miRNAs in BMDd45-55 muscular biopsies using TLDA and an in silico study to determine which one could target nNOS, we selected four miRNAs. In order to select those that targeted a sequence of 3'UTR of NOS1, we performed luciferase gene reporter assay in HEK393T cells. Finally, expression of candidate miRNAs was modulated in control and DMD human myoblasts (DMDd45-52) to study their ability to target nNOS. RESULTS:TLDA assay and the in silico study allowed us to select four miRNAs overexpressed in muscle biopsies of BMDd45-55 compared to controls. Among them, only the overexpression of miR-31, miR-708, and miR-34c led to a decrease of luciferase activity in an NOS1-3'UTR-luciferase assay, confirming their interaction with the NOS1-3'UTR. The effect of these three miRNAs was investigated on control and DMDd45-52 myoblasts. First, we showed a decrease of nNOS expression when miR-708 or miR-34c were overexpressed in control myoblasts. We then confirmed that DMDd45-52 cells displayed an endogenous increased of miR-31, miR-708, and miR-34c and a decreased of nNOS expression, the same characteristics observed in BMDd45-55 biopsies. In DMDd45-52 cells, we demonstrated that the inhibition of miR-708 and miR-34c increased nNOS expression, confirming that both miRNAs can modulate nNOS expression in human myoblasts. CONCLUSION:These results strongly suggest that miR-708 and miR-34c, overexpressed in dystrophic context, are new actors involved in the regulation of nNOS expression in dystrophic muscle.

Dataset Information

Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis.

Background

Methods

Results

Conclusion

Publications

Synergistic effects of miR-708-5p and miR-708-3p accelerate the progression of osteoporosis.

Similar Datasets

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