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Treadmill training regulates bone metabolism and osteogenic differentiation(miRNA Array)

ABSTRACT: MicroRNAs (miRNAs) are important in the process of exercise influencing bone metabolism. The present study aimed to detect and select differentially expressed miRNAs in the bone tissues of mice trained on a treadmill, predict the target genes of these differentially expressed miRNAs and lay a foundation for exploring the effect of treadmill training on bone metabolism through miRNAs. In this experiment, after the mice were trained on a treadmill for 8 weeks, the mechanical properties of mouse femur bone were assessed, and the alkaline phosphatase (ALP) activity and osteocalcin (OCN) protein levels of the bone were assayed. miRNA microarray and reverse transcription-quantitative (RT-q)PCR were performed to select and validate differentially expressed miRNAs in the bone, and the target genes of these miRNAs were predicted with bioinformatics methods. In addition, the differentially expressed miRNAs in the bone tissues were compared with those in mechanically strained osteocytes in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE179201 | GEO | 2021/07/02

REPOSITORIES: GEO

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Project description:MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period. Here we monitored the transcriptome changes by microarray analysis of the whole blood of eight highly trained athletes after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and then mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation. We have identified four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation. Each subject performed a treadmill test with an incremental step protocol until exhaustion. Blood samples were taken from the antecubital vein using indwelling catheter before (T1), immediately after ramp test to exaustion (T2) and after 30 min of recovery (T3). Two weeks later, athletes participated in the main exercise, consisting of running at 80% VO2 peak for 30 min on a treadmill. Blood samples were taken from the antecubital vein using indwelling catheter before (T4), immediately after running at 80% VO2 peak for 30 min on a treadmill (T5), after 30 min (T6) and 60 min (T7) of recovery.

Project description:Purpose: Using RNA-sequencing technology to screen the effect of moderate-intensity treadmill exercise on the key genes that affect bone mass in the peripheral blood mononuclear cells (PBMCs) of ovariectomized (OVX) rats. Methods: Three-month-old female Sprague–Dawley rats of Specific Pathogen Free (SPF) grade were randomly divided into the sham operation (SHAM) group, OVX group, and OVX combined exercise (OVX+EX) group. The OVX+EX group performed moderate-intensity treadmill exercise for 17 weeks. Upon completion of these exercises, the body composition and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry, and the bone microstructure of the femur was observed using micro-computed tomography scanning. PBMCs were collected from the abdominal aorta, and the differential genes were analyzed by transcriptome sequencing. The Metascape software was used for gene ontology and pathway enrichment analysis to further screen key genes. Results: 1. In the OVX group, the body weight and body fat content were significantly higher than in the SHAM group and the body muscle content and BMD were significantly lower. 2. The trabecular bone parameters in the OVX group were significantly lower than in the SHAM group, and they were significantly higher in the OVX+EX group than in the OVX group. When compared with the SHAM group, the microstructure of the distal femur trabecular in the OVX group was severely damaged, the trabecular bones were sparse, and there was a large gap between the trabecular bones. The number and continuity of the trabecular bones were higher in OVX+EX group than in the OVX group. 3. A Venn diagram showed that there were 58 common differential genes, with a fold change ≥2 and p value <0.05. and the differential genes were mainly enriched in the PI3K-Akt signaling pathway. Five key genes were screened including CCL2, Nos3, Tgfb3, ITGb4, and LpL. Conclusion: Moderate-intensity treadmill exercise may improve the body composition and bone mass of the OVX group by upregulating CCL2 and other genes of the PBMC. The results also showed that the PBMCs in the peripheral blood can be a useful tool for monitoring the effect of exercise on bone health in postmenopausal osteoporosis.

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Treadmill training regulates bone metabolism and osteogenic differentiation(miRNA Array)

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