Department of Medicine/Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Gene. 2012 Jan 15;492(1):1-18. doi: 10.1016/j.gene.2011.10.044. Epub 2011 Nov 3.
For more than a decade, Wnt signaling pathways have been the focus of intense research activity in bone biology laboratories because of their importance in skeletal development, bone mass maintenance, and therapeutic potential for regenerative medicine. It is evident that even subtle alterations in the intensity, amplitude, location, and duration of Wnt signaling pathways affects skeletal development, as well as bone remodeling, regeneration, and repair during a lifespan. Here we review recent advances and discrepancies in how Wnt/Lrp5 signaling regulates osteoblasts and osteocytes, introduce new players in Wnt signaling pathways that have important roles in bone development, discuss emerging areas such as the role of Wnt signaling in osteoclastogenesis, and summarize progress made in translating basic studies to clinical therapeutics and diagnostics centered around inhibiting Wnt pathway antagonists, such as sclerostin, Dkk1 and Sfrp1. Emphasis is placed on the plethora of genetic studies in mouse models and genome wide association studies that reveal the requirement for and crucial roles of Wnt pathway components during skeletal development and disease.
十多年来，Wnt 信号通路一直是骨骼生物学实验室研究的重点，因为它们在骨骼发育、骨量维持以及再生医学的治疗潜力方面具有重要作用。很明显，即使是 Wnt 信号通路的强度、幅度、位置和持续时间的微小改变，也会影响骨骼发育以及整个生命周期中的骨重塑、再生和修复。在这里，我们回顾了 Wnt/Lrp5 信号如何调节成骨细胞和破骨细胞的最新进展和差异，介绍了在骨骼发育中具有重要作用的 Wnt 信号通路的新成员，讨论了 Wnt 信号在破骨细胞生成中的作用等新兴领域，并总结了围绕抑制 Wnt 通路拮抗剂（如骨硬化蛋白、DKK1 和 SFRP1）的基础研究向临床治疗和诊断转化所取得的进展。重点强调了大量的小鼠模型和全基因组关联研究，这些研究揭示了 Wnt 通路成分在骨骼发育和疾病中的必要性和关键作用。
