骨质疏松以进行性骨丢失、骨强度下降为特征，易并发腰椎及髋部骨折，严重危害中老年人生命健康。骨吸收增强是骨质疏松发生的重要原因，破骨细胞肌动蛋白环在骨吸收中扮演主要作用，但其调节机制尚未明确。申请者前期研究发现， Nucleolin（NCL）在骨丢失患者血清中高表达，并与骨密度相关，进一步实验表明，NCL可以结合细胞骨架调节蛋白Wiskott–Aldrich Syndrome protein （WASP）的mRNA，可能是破骨细胞骨吸收封闭环调控的关键环节。申请者拟通过本项目着力解决以下问题：（1）NCL与WASP mRNA的亚细胞定位及结合位点；（2）NCL介导WASP调控破骨细胞肌动蛋白环的作用机制；（3）破骨细胞肌动蛋白环在骨丢失进程中成分与功能的动态变化；基于以上研究结果，申请者拟利用动物模型进一步探索NCL作为进行性骨丢失患者早期诊断标志物和药物靶点的可行性。

Osteoporosis is characterized by progressive bone loss and decreased bone strength, which is easy to be complicated with spinal and hip fractures and seriously endangers the life and health of elderly people. Excessive enhancement of bone resorption is the main cause of osteoporosis. Osteoclast actin ring plays an important role in bone resorption, but its regulatory mechanism is still unclear. Our previous studies found that Nucleolin (NCL) was continuously highly expressed in serum of patients with osteopenia and osteoporosis, further experiments proved that NCL could bind to mRNA of nucleation promoting protein WASP, which was speculated to be a key factor in regulating the function of osteoclast actin ring. We intend to elucidate the following questions through the present study: (1) binding sites and subcellular localization of NCL and WASP mRNA; (2) the mechanism of NCL-mediated WASP regulation of osteoclast actin ring; (3) dynamic changes of composition and function of osteoclast actin ring in the process of bone loss; Based on the above results, we intend to further explore the feasibility of NCL as early diagnostic markers and therapeutic targets for patients with bone loss.