Osteoporosis, a prevalent systemic bone disease, has emerged as one of the most complicated health issues due to the risk of increased susceptibility to fractures. Bone-marrow mesenchymal stem cell (BMSC) has great potential of differentiating into several distinct cell types, including osteoblasts, adipocytes and chondrocytes. The present study analyzed the biological function changes of BMSCs under osteoporotic micro-environment and aimed to find a specific mechanism associated with this condition. Female rats were assigned to two groups: sham operation (SHAM) group and ovariectomy (OVX) group. BMSCs were harvested and cultured in vitro after 3 months post-ovariectomy. Alamar-Blue test suggested a higher proliferation ability in SHAM group. The differentiation potential of BMSCs was verified through various assays in vitro. RT-PCR and western blot analysis further confirmed the lower osteogenic and adipogenic differentiation capacity in OVX group. Moreover, through the microarray analysis, we were stunned to find that Integrin Alpha-7 (ITGA7) may improve osteogenesis through phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathway. Overall, our study showed that osteoporosis inhibited the proliferation and differentiation of BMSCs, especially the osteogenesis and adipogenesis. Meanwhile, modulation of ITGA7 expression through PI3K/Akt signaling pathway might provide a new therapeutic target for osteoporosis. (C) 2020 Elsevier Inc. All rights reserved.