Differentiated embryo-chondrocyte expressed gene 1 (DEC1) is associated with chondrogenesis, neurogenesis, immune response, biological rhythm, lipogenesis, cell differentiation and carcinogenesis. However, there is little information about its contribution to osteoblast osteogenesis. In the present study, we report that DEC1 expression increases along with the degree of mineralization, which parallells with the increase of osteogenesis induction time in SaoS-2 cells. Dexamethasone (DEX) decreases the osteogenesis capacity such as alkaline phosphatase (ALP) activity and mineralization along with decreasing the DEC1 expression. On the contrary, 17β-estradiol (E2) increases the osteogenesis along with increasing the DEC1 expression. Moreover, the overexpression of DEC1 alone increases the ALP activity and mineralization synchronously, and it not only partially reverses the decrease of ALP activity induced by DEX, but almost abolishes the decrease of mineralized nodules induced by DEX. On the other hand, the DEC1 expression decreases in tibia bone marrow side of ovariectomy mice compared with that in sham-operated mice, and E2 treatment ameliorates the decrease of DEC1 expression induced by bilateral ovariectomy and prevents osteoporosis in ovariectomized mice . Taken together, downregulation of DEC1 expression is related to the decrease of osteogenic capacity. The findings provide a novel target for the therapy of osteoporosis.