Wnts are secreted, lipid-modified proteins that bind to different receptors on the cell surface to activate canonical or non-canonical Wnt signaling pathways, which control various biological processes throughout embryonic development and adult life. Aberrant Wnt signaling pathway underlies a wide range of human disease pathogeneses. In this review, we provide an update of Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and diseases. The Wnt proteins, receptors, activators, inhibitors, and the crosstalk of Wnt signaling pathways with other signaling pathways are summarized and discussed. We mainly review Wnt signaling functions in bone formation, homeostasis, and related diseases, and summarize mouse models carrying genetic modifications of Wnt signaling components. Moreover, the therapeutic strategies for treating bone diseases by targeting Wnt signaling, including the extracellular molecules, cytosol components, and nuclear components of Wnt signaling are reviewed. In summary, this paper reviews our current understanding of the mechanisms by which Wnt signaling regulates bone formation, homeostasis, and the efforts targeting Wnt signaling for treating bone diseases. Finally, the paper evaluates the important questions in Wnt signaling to be further explored based on the progress of new biological analytical technologies.

Wnt 是分泌型脂质修饰蛋白，可与细胞表面的不同受体结合，激活经典或非经典 Wnt 信号通路，控制整个胚胎发育和成年生命中的各种生物过程。异常的 Wnt 信号通路是多种人类疾病发病机制的基础。在这篇综述中，我们提供了 Wnt/β-连环蛋白信号传导成分和骨形成、稳态和疾病机制的最新信息。对Wnt蛋白、受体、激活剂、抑制剂以及Wnt信号通路与其他信号通路的串扰进行了总结和讨论。我们主要综述Wnt信号在骨形成、稳态和相关疾病中的功能，并总结携带Wnt信号元件基因修饰的小鼠模型。此外，还综述了针对Wnt信号传导治疗骨疾病的治疗策略，包括Wnt信号传导的细胞外分子、细胞质成分和核成分。总之，本文回顾了我们目前对 Wnt 信号调节骨形成、稳态的机制的理解，以及针对 Wnt 信号传导治疗骨疾病的努力。最后，本文根据新的生物分析技术的进展，评估了Wnt信号传导中有待进一步探讨的重要问题。