Abstract: Objective：Search for the key miRNA that regulate mouse bone marrow stromal stem cells (mBMSCs) osteogenesis in the microenviroment of estrogen-deficiency-induced osteoporosis.To investigate the key miRNA whether involved in the osteogenic differentiation of mBMSCs and the effect in this progress in estrogen-deficiency-induced osteoporosis.Methods：An ovariectomized animal model was employed. Screen the key miRNA through combination of bioinformatics methods and microRNA gene chip technology in the mBMSCs derived from OVX and Sham mice. Real-time RT-PCR was used to detect the levels of key miRNA in these types of mBMSCs. The miR-21 function was investigated by transfecting pre-miR-21 and anti-miR-21 into mBMSCs. And osteogenic gene and protein expression was determined by Alizarin Red S, Oil red O staining, real-time RT-PCR and Western blot analysis, respectively.Results：OVX model were sucessfully build. And miR-21 were screened. Real-time RT-PCR shows that miR-21 in OVX-mBMSCs decreased compared with Sham-mBMSCs. Upregulation miR-21 in OVX-mBMSCs. Real-time RT-PCR, Western blot, Alizarin Red S and ALP staining suggested the potential osteogenesis of mBMSCs were enhanced..Conclusions：miR-21 was the key miRNA that regulate mBMSCs osteogenesis in the microenviroment of estrogen-deficiency-induced osteoporosis. And miR-21could promote the potential of mBMSCs in nomal and estrogen deficiency-induced osteoporosis.