The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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Rapamycin has been reported to be immunosuppressive and anti-proliferative towards vascular endothelial and smooth muscle cells. The purpose of the present study was to investigate the effects of rapamycin on the biological behaviors of endothelial cells that have been separated from the deformed vein in human venous malformation (VM). Cellular morphology was observed using inverted microscopy. An MTT assay was performed to measure the cell viability at different concentrations of rapamycin and different time points. Cell apoptosis and migration were detected using a terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assay and a wound-healing assay, respectively. At 48 and 72 h, rapamycin inhibited proliferation of human VM endothelial cells, with the effects becoming more pronounced with increasing concentration. Only rapamycin at a concentration of 1,000 ng/ml had a significant effect at 24 h in repressing proliferation. At 48 h, compared with the blank group, the majority of cells maintained a clear nuclear boundary and a regular shape following treatment with 1 ng/ml rapamycin; 10 and 100 ng/ml rapamycin caused desquamation and rounded shape; and 1,000 ng/ml rapamycin caused even more marked desquamation, rounded shape and necrosis. Rapamycin at concentrations of 1, 10, 100 and 1,000 ng/ml reduced cell viability, increased the number of apoptotic cells and suppressed the migration capacity of human VM endothelial cells, and the effects became more pronounced with increasing concentration, when compared with the blank group. These findings provide evidence that rapamycin induces apoptosis and inhibits proliferation and migration of human VM endothelial cells in a concentration-dependent manner.