RANKL is a key molecule that bridges the bone and immune systems. RANKL stimulation activates a signaling pathway downstream of RANK, thereby determining the extent of bone resorption by inducing osteoclast maturation. The signaling pathway also regulates the development of different lymphoid organs, including the thymus, lymph nodes, and Peyer's patches, and plays an essential role in the establishment of immune tolerance. Such characteristics have continued to attract the attention of many researchers, even though it is now more than 20 years since RANKL was identified as a novel member of the TNF superfamily. Recently, we found that RANKL can function not only as a signal input molecule but also as a signal receptor to activate the RANKL reverse signaling pathway, which mediates the coupling between bone resorption and formation. This new finding may provide an important basis for elucidating the complex physiological roles played by RANKL.

RANKL 是连接骨骼和免疫系统的关键分子。RANKL 刺激激活 RANK 下游的信号通路，从而通过诱导破骨细胞成熟来确定骨吸收的程度。该信号通路还调节不同淋巴器官的发育，包括胸腺、淋巴结和派尔斑，并在免疫耐受的建立中发挥重要作用。尽管 RANKL 被确定为 TNF 超家族的新成员已有 20 多年的历史，但这些特征一直吸引着许多研究人员的注意。最近，我们发现RANKL不仅可以作为信号输入分子，还可以作为信号受体激活RANKL反向信号通路，介导骨吸收和形成之间的耦合。