申请者基于前期两种骨质疏松小鼠模型（双侧卵巢切除、大剂量皮质激素）DEC1表达明显减少；雌激素和淫羊藿苷分别处理两种骨质疏松小鼠模型后，均能改善小鼠骨质疏松症状，同时亦可明显逆转DEC1表达降低的作用；大剂量地塞米松（>0.5-1μM）所致细胞骨质疏松模型，其成骨能力明显下降，同时伴DEC1明显降低；过度表达DEC1(能)取消地塞米松的所致成骨细胞成骨能力降低作用。因此，提出DEC1在成骨细胞成骨分化过程中可能发挥重要调控作用的假设。本项目应用DEC1基因敲除小鼠、原代培养成骨细胞和骨髓间充质干细胞为研究模型，运用分子克隆技术、现代分子生物学等方法，从整体、细胞和分子水平，研究并阐明DEC1对成骨细胞成骨分化中的调控作用和分子机制以及DEC1在药物抗骨质疏松作用中的作用机制和意义。预期研究结果不仅拓展DEC1在骨代谢的研究领域，且为预防和治疗骨质疏松药物的研发提供新的靶标。

Based on the following data we had gotten: (1) The differentiated embryonic chondrocytes 1 (DEC1) expression significantly decreased in both two types of osteoporotic mice induced by bilateral ovariectomy and glucocorticoid. (2) 17-estradiol (E2) and icariin treatment can reverse the decrease of DEC1 expression and prevent the bilateral ovariectomy and glucocorticoid induced osteoporosis respectively. (3) Dexamethasone (DEX) decreases the osteogenesis capacity such as alkaline phosphatase (ALP) activity and mineralization along with decreasing the DEC1 expression in the osteoblasts (Saos-2). On the contrary, E2 increases the osteogenesis along with increasing the DEC1 expression in the osteoblasts. (4) 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. Therefore, it is hypothesized that DEC1 probably plays a critical role in the osteogenic differentiation of osteoblasts. Form the whole, the cell and molecule levels, this study will investigate the regulation and mechanism of DEC1 in the osteogenesis of osteoblasts, and the mechanism and significance of DEC1 in the anti-osteoporosis effects produced by anti-osteoporosis drugs using knockout DEC1 mice, the overexpression and knockdown of DEC1 in the osteoblasts, primary cultured mouse osteoblasts and mesenchymal stem cells. Expected outcome will reveal the regulation and mechanism of DEC1 in the osteogenesis of osteoblasts, and the mechanism and significance of DEC1 in the anti-osteoporosis effects produced by anti-osteoporosis drugs. This study not only expands the DEC1 in the research field of bone metabolism academically, but also provides a molecular target therapy and the anti-osteoporosis drugs development based on DEC1.