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OBJECTIVE This study aimed to investigate the expression of miR-373 in osteoporosis patients and rat models induced by estrogen deficiency and to detect whether miR-373 can regulate the ability of osteogenic differentiation of bone marrow mesenchymal stem cells in the osteoporosis microenvironment caused by estrogen deficiency. PATIENTS AND METHODS Bone tissues and blood samples were collected from 20 osteoporotic patients and 20 controls. PCR analysis was used to detect the expression of miR-373 in bone tissue and serum from postmenopausal osteoporotic patients and normal patients. 120 SD rats were purchased and randomly divided into sham operation group and OVX group. Rat models of sham-operated and bilateral oophorectomy mice models were constructed. The expression of miR-373 in bone tissue, cells, and serum of the mice was tested. Then, bone marrow mesenchymal stem cells from sham-operated rats and bilaterally ovariectomized rats were isolated and cultured. After 10 days of osteogenic induction, alkaline phosphatase staining and alizarin red staining were performed to test the osteogenic differentiation ability of bone marrow mesenchymal stem cells, and whether miR-373 affects this ability. RESULTS PCR results showed that the expression of miR-373 in the bone tissue and the serum of patients with postmenopausal osteoporosis was significantly reduced. The expression of miR-373 was markedly decreased in the bone tissue, cells, and serum from the rats of bilateral ovariectomy group. Alkaline phosphatase staining and alizarin red staining showed that miR-373 could promote the differentiation of bone marrow mesenchymal stem cells into osteoblasts and reverse the decreased osteogenic differentiation of bone marrow mesenchymal stem cells caused by osteoporosis. CONCLUSIONS The expression of miR-373 is decreased in osteoporotic patients and rat models caused by estrogen deficiency, and it can promote the differentiation of bone marrow mesenchymal stem cells into the osteogenic direction. This work provides a new direction and experimental basis for clinical diagnosis and treatment of osteoporosis.