<p>Osteoporosis is partially characterized by the shifted differentiation of bone marrow mesenchymal stem cells (BMSCs) towards adipocytes and away from osteoblasts. This study aims to investigate the role of vascular endothelial cell (HMEC-1) exosomes in regulating the osteogenic and adipogenic differentiation of mouse BMSCs, specifically focusing on the involvement of miR-5p-13348_267. Primary BMSCs were cultured under conditions inducing osteogenic or adipogenic differentiation. Alizarin red staining was used to visualize osteogenic mineralized calcium nodules, while oil red O staining was employed to observe lipid droplet formation. MiRNA sequencing was performed to identify miR-5p-13348_267 as a differentially expressed miRNA in HMEC-1 exosomes and HMEC-1 cells. The direct target genes of miR-5p-13348_267 were analyze and filtered by bioinformatics analysis. MiRNA sequencing revealed miR-5p-13348_267 as a key miRNA in HMEC-1 exosomes regulating the differentiation fate of BMSCs. Overexpression of miR-5p-13348_267 significantly enhanced calcium mineralization during osteogenic differentiation of BMSCs and reduced lipid droplet formation during adipogenic differentiation. Overexpressed miR-5p-13348_267 upregulated the expression of osteogenic differentiation-related genes ALP and OC, while downregulating the expression of adipogenic differentiation-related genes mPparg and CD36, as well as the senescence-related gene P16. Bioinformatics analysis identified the top 10 targets of miR-5p-13348_267 involved in regulating the osteogenic-adipogenic differentiation of BMSCs. Our findings suggest that HMEC-1 drived exosomes miR-5p-13348_267 promote the osteogenic differentiation of BMSCs and inhibit their adipogenic differentiation. This mechanism may play a role in slowing down the progression of osteoporosis.</p>