Mechanism of dexmedetomidine regulating osteogenesis-angiogenesis coupling through the miR-361-5p/VEGFA axis in postmenopausal osteoporosis

Aims: Postmenopausal osteoporosis (PMOP) is a growing health problem affecting many postmenopausal women. This study intended to identify the role of dexmedetomidine (Dex) in osteoporosis (OP).Main methods: Microarray analysis was performed for the gene expression profiles of PMOP patients and postmenopausal healthy volunteers, and the most differentially expressed microRNA (miR)-361-5p was verified in clinic, and its diagnostic value in PMOP patients was analyzed. After establishment of OP model by ovariectomy, Dex treatment and overexpression of miR-361-5p or vascular endothelial growth factor A (VEGFA) were performed in OP rats or isolated bone marrow mesenchymal stem cells (BMSCs). Bone mineral density (BMD) related indexes and levels of osteogenesis-angiogenesis related genes were measured. The apoptosis and osteogenic differentiation of BMSCs were detected. After human umbilical vein endothelial cells (HUVECs) and BMSCs were cocultured, the angiogenesis of BMSCs was detected by Matrigel-based angiogenesis experiment.Key findings: miR-361-5p was highly expressed in PMOP patients and OP rats, with good diagnostic effect on PMOP. After Dex treatment, the expressions of miR-361-5p, VEGFA, BMD related indexes were increased in OP rats. In BMSCs, level of osteogenesis-angiogenesis related genes were increased after adding Dex, and the apoptosis was decreased after coculture of HUVECs and BMSCs. miR-361-5p could target VEGFA. After miR-3615p overexpression + Dex treatment, the indexes related to osteogenesis and angiogenesis in OP rats and BMSCs were decreased, which were reversed after further overexpressing VEGFA.Significance: Dex can enhance VEGFA by inhibiting miR-361-5p, and then promote osteogenesis-angiogenesis, thus providing potential targets for PMOP treatment.