骨质疏松（OP）已成为目前造成家庭和社会沉重负担的常见病。申请者基于前期发现DEC1 敲除（KO）各年龄（4、24、52周龄）小鼠骨组织NFATc-1及下游靶基因表达较同年龄野生（WT）小鼠明显降低，尤以24周龄小鼠表现最为明显；52周龄KO小鼠出现骨量增加；在KO小鼠骨髓巨噬细胞诱导破骨细胞分化过程中NFATc-1及下游靶基因表达和破骨细胞形成均较WT小鼠明显降低的基础上，提出DEC1通过NFATc-1促进破骨细胞分化的假设。本项目拟用WT、KO小鼠制备OP和LPS诱导颅骨溶骨模型、两种基因型小鼠骨髓巨噬细胞制备LPS诱导模型，应用分子克隆技术、现代分子生物学等方法，研究并阐明DEC1通过激活NFATc-1对破骨细胞分化调控作用和机制以及在OP发生发展中的作用，揭示以DEC1为靶标药物实验治疗学意义，本项目不仅有助于深化对OP病因学的认识，也为研发DEC1拮抗剂治疗OP积累学术基础。

Recently, osteoporosis (OP) is one of the most common diseases which cause huge societal and family burdens. Based on the following data we had gotten: (1) NFATc-1 and targets TRAP, CTSK and MPP9 of proximal tibia at different ages (4, 24, 52 weeks) significantly decreased in DEC1 KO (DEC1-/-) mice compared with those in WT (DEC1+/+) mice, especially at 24 weeks old mice. (2) In osteoclast differentiation of bone marrow macrophages (BMMs) from DEC1+/+ and DEC1-/- mice, NFATc-1, CTSK and MPP9 significantly decreased along with decrease of osteoclast formation from KO mice compared with those from WT mice. Therefore, it is hypothesized that DEC1 promotes osteoclast differentiation through enhancing NFATc-1. Making two types of osteoporosis model and LPS-induced calvarial model with WT and KO (DEC1+/+, DEC1-/-) mice, and making LPS-induced model with the primary cultured bone marrow mononuclear cells(BMMs), we will, on the systemic and the cellular levels, investigate the regulation and mechanism of DEC1 on promoting the osteclast differentiation through enhancing NFATc-1, which plays a role in the developing of OP, through using molecular cloning technology and modern molecular biology methods. Expected outcome will reveal the regulation and mechanism of DEC1 on promoting the osteclast differentiation through enhancing NFATc-1. This study not only deepens understanding the etiology of OP, but also provides academic evidence on developing a DEC1 antagonist for treatment of OP.