牙槽骨骨重塑是正畸牙移动的生物学基础。Wnt通路的拮抗剂骨硬化蛋白（Sclerostin/SOST）在骨重塑中扮演重要角色，其表达受BMP信号通路调控，但具体分子机制尚不清楚。研究表明，肌细胞增强因子2C（Mef2C）能通过增强子ECR5调节SOST表达，而敲除成骨细胞的 BMP1型受体A（BMPR1A），SOST与Mef2C的表达均下调。本课题以Mef2C为切入点，拟构建骨细胞特异性BMPR1A敲除小鼠，同时对骨细胞株MLO-A5进行基因转染和RNA干扰，检测BMP-Smad通路和Mef2C-ECR5-SOST转录轴各级信号分子的表达，以探索BMPs调节SOST表达的分子机制。本课题的成功实施，将揭示BMP通路与Wnt通路之间的串话机制，可望通过靶向干预Mef2C-ECR5-SOST转录轴来调节骨重塑进程，对实现BMPs在安全、高效的正畸牙移动和骨缺失类疾病治疗中的转化应用具有重要意义。

Efficient alveolar bone remodeling is the biological basis for safe and rapid orthodontic tooth movement. As an extracellular antagonist of Wnt signaling pathway, Sclerostin/SOST plays an important regulatory role in bone remodeling process, and is controlled by bone morphogenic proteins (BMPs). However, the exact molecular mechanism involved is still undefined. Recent studies reported that myocyte enhancer factor 2C (Mef2C) could regulate SOST expression via evolutionarily conserved regions 5 (ECR5). Our previous studies found that conditional knockout of BMP receptor type IA (BMPR1A) in osteoblasts led to significant down-regulation of SOST and Mef2C expression. In order to explore the mechanism involved in the regulation of BMPs on SOST expression, we plan to establish the mouse model of conditional knockout of BMPR1A in osteocytes by mating SOST-Cre mice with BMPR1Aflox/flox mice, and investigate the expressions of various signaling molecules of BMP pathway and Mef2C-ECR5-SOST transcriptional axis both in vitro and in vivo. The successful implementation of this project would unveil the crosstalk between BMP pathway and Wnt pathway, which might be helpful to the effective interference of bone remodeling by targeted promotion or inhibition of Mef2C-ECR5-SOST transcriptional axis, and brings about new approaches to facilitating alveolar bone remodeling during treatment of orthodontics and bone-loss diseases.