Abstract
ObjectivesExposure to microgravity induces many adaptive and pathological changes in human bone marrow mesenchymal stem cells (hBMSCs). However, the underlying mechanisms of these changes are poorly understood. We revealed the gene expression patterns of hBMSCs under normal ground (NG) and simulated microgravity (SMG), which showed an interpretation for these changes by gene regulation and signal pathways analysis.Materials and methodsIn this study, hBMSCs were osteogenically induced for 0, 2, 7 and 14 days under normal ground gravity and simulated microgravity, followed by analysis of the differences in transcriptome expression during osteogenic differentiation by RNA sequencing and some experimental verification for these results.ResultsThe results indicated that 837, 399 and 894 differentially expressed genes (DEGs) were identified in 2, 7 and 14 days samples, respectively, out of which 13 genes were selected for qRT‐PCR analysis to confirm the RNA‐sequencing results. After analysis, we found that proliferation was inhibited in the early stage of induction. In the middle stage, osteogenic differentiation was inhibited, whereas adipogenic differentiation benefited from SMG. Moreover, SMG resulted in the up‐regulation of genes specific for tumorigenesis in the later stage.ConclusionOur data revealed that SMG inhibits the proliferation and inhibits the differentiation towards osteoblasts but promotes adipogenesis. SMG also selects highly tumorigenic cells for survival under prolonged SMG.
Highlights
Previous studies have shown that microgravity induces significant bone loss in weight‐bearing bones at a rate of approximately 1%‐2% per month.[1]
On day 2, human bone marrow mesenchymal stem cells (hBMSCs) cultured under simulated mi‐ crogravity (SMG) exhibited down‐regulation of the genes related to cell cycle, such as MCM5, CCNA2, CCNB1, CDK1, E2F1, CDC25B and CDC25C.16-22
The decrease in the above genes and the change of the cytoskeleton resulted in the arrest of the cell cycle in S phase and G2/M transitions, and the interaction of these changes led to an increase in the proportion of cells in S and G2/M
Summary
Previous studies have shown that microgravity induces significant bone loss in weight‐bearing bones at a rate of approximately 1%‐2% per month.[1]. Micro‐ gravity causes an increase in bone resorption by osteoclasts and a decrease in osteoblast cellular integrity.[4] Microgravity has a significant effect on cell proliferation. Mouse embryonic stem (ES) cells cultured under the SMG condition had a significantly reduced. We performed an RNA‐seq analysis of hBMSCs induced osteogenically under SMG and NG, and clustered differentially ex‐ pressed genes (DEGs) into several functional groups to analyse the impacts of SMG on the physiology of hBMSCs
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