Abstract:
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.
摘要:
Wnts是分泌的,与细胞表面不同受体结合以激活经典或非经典Wnt信号通路的脂质修饰蛋白,它控制着整个胚胎发育和成年期的各种生物过程。异常的Wnt信号通路是广泛的人类疾病致病机制的基础。在这次审查中,我们提供了Wnt/β-catenin信号传导成分和骨形成机制的最新信息,稳态,和疾病。Wnt蛋白,受体,活化剂,抑制剂,并对Wnt信号通路与其他信号通路的串扰进行了总结和讨论。我们主要综述了Wnt信号在骨形成中的功能,稳态,和相关疾病,并总结了携带Wnt信号传导成分遗传修饰的小鼠模型。此外,通过靶向Wnt信号治疗骨疾病的治疗策略,包括细胞外分子,胞质溶胶成分,并对Wnt信号的核成分进行了综述。总之,本文回顾了我们目前对Wnt信号调节骨形成的机制的理解,稳态,以及靶向Wnt信号用于治疗骨疾病的努力。最后,本文结合生物分析新技术的进展,对Wnt信号中有待进一步探讨的重要问题进行了评价。