通过抑制破骨细胞（OC）治疗骨质疏松症过程中往往伴随成骨细胞（OB）活性减弱，提示OC与OB功能存在偶联，但机制不清。现已明确RANKL-RANK途径是OB调控OC活性的关键通路。研究表明，RANK-RANKL逆向信号对T细胞功能有重要影响，但在骨代谢中未见相关报道。我们前期研究提示RANK可促进OB的功能，且此效应依赖RANKL。本项目中我们首次提出：OC可通过RANK-RANKL逆向信号反馈促进OB的功能，这种反馈促进作用的减弱是骨质疏松症的原因之一。我们拟研究RANKL逆向信号通路的具体信号传导途径和机制，比较骨质疏松患者和正常人OB中RANKL逆向信号通路各组分的活性，寻找骨质疏松症患者RANKL逆向信号通路活性降低的原因，并在小鼠骨质疏松症模型上尝试通过恢复RANKL逆向信号通路活性的办法防治骨质疏松症。本研究将为理解OB与OC相互调控机制及抗骨质疏松治疗提供新的思路。

The functions of the osteoblast and osteoclast are coupled, and the imbalance of osteoblast and osteoclast will lead to diseases, for instance, osteoporosis. It is widely accepted that osteoblast regulates osteoclast through RANKL (Receptor Activator of Nuclear factor Kappa-B Ligand)-RANK pathway. However, how osteoclast feedback regulates osteoblast is still unclear. The latest researches indicate that RANKL on T cell can transduce reverse signal to regulate T cell. Therefore, we speculated that RANKL on osteoblast could also transduce reverse signal to regulate osteoblast. The reverse signal of osteoclast may be a potential way to regulates osteoblast by osteoclast. Our preliminary study confirmed that RANK could promote the proliferation and differentiation of osteoblast. To study the mechanism of the RANK-RANKL reverse signal on osteoblast, we design a full set of experiments. The research will uncover mechanisms of the osteoblast and osteoclast's interaction. The RANK-RANKL reverse signal theory will shine light on the treatment of osteoporosis.