Exercise rejuvenates bone marrow mesenchymal stem cells associated with the inhibition of inflammatory factors and senescence-related factors.

OBJECTIVE

To investigate the effects of exercise on bone marrow stem cells (BMSCs) and determine underlying molecular network mechanisms through bioinformatics analysis combined experimental validation.

METHODS

Target genes related to exercise and BMSCs were retrieved from the Gene Cards database and deduplicated, then performed bioinformatics analysis including Venny analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and cystoscope to find hub genes. In animal experiment, 9-month-old male C57BL/6J mice were subjected to 4 months of treadmill exercise training (12 m/min, 1 h/day, 5 days/week) and the BMSCs from femur were cultured in vitro, and cell viability, the expression of cell senescence-related factors (P16, P21) and inflammatory factors (IL-6, IL-1β) were detected, and the vital role of IL-6, IL-1β was determined in vitro study.

RESULTS

131 common targets were found via Venn diagram analysis. The STRING database and Cytoscape software identified several core molecules such as IL-1β, IL6, TNF, and stat3, etc. GO enrichment analysis revealed that these common targets were primarily involved in biological processes such as negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway, leukocyte chemotaxis, and positive regulation of protein phosphorylation; cellular components such as extracellular space and lysosome; and molecular functions such as receptor ligand activity and chemokine activity. KEGG pathway analysis showed that the related genes were enriched in pathways including diabetic cardiomyopathy, IL-17 signaling pathway, and HIF-1 signaling pathway. Moreover, treadmill exercise results in a significant cell viability increase, which is related to the inhibition of IL-1β, IL-6 and P16, P21. Whereas the knockdown of IL-1β, IL-6 confirmed their vital role in the status of BMSC's rejuvenation.

CONCLUSION

The present data concluded that running exercise increase effectively the physical viability to rejuvenate BMSCs, and underlying mechanism is associated with the inhibition of inflammatory factors and senescence-related factors.