Update on Wnt signaling in bone cell biology and bone disease.

Update on Wnt signaling in bone cell biology and bone disease.
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DOI:
10.1016/j.gene.2011.10.044
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发表时间:
2012-01-15
期刊:
影响因子:
3.5
通讯作者:
Westendorf JJ
Westendorf JJ
中科院分区:
生物学3区
文献类型:
--
作者:
Monroe DG;McGee-Lawrence ME;Oursler MJ;Westendorf JJ

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十多年来,Wnt信号通路一直是骨生物学实验室密集研究活动的焦点,因为它们在骨骼发育,骨量维持和再生医学治疗潜力中的重要性。很明显,即使Wnt信号通路的强度、振幅、位置和持续时间发生微小变化,也会影响骨骼发育,以及骨重建、再生和修复。在这里,我们回顾了Wnt/Lrp 5信号如何调节成骨细胞和骨细胞的最新进展和差异,介绍了在骨发育中发挥重要作用的Wnt信号通路中的新参与者,讨论了新兴领域,如Wnt信号在破骨细胞生成中的作用,并总结了将基础研究转化为临床治疗和诊断的进展,这些临床治疗和诊断以抑制Wnt通路拮抗剂为中心,如sclerostin,Dkk 1和Sfrp 1。重点放在小鼠模型和全基因组关联研究中的大量遗传研究上,这些研究揭示了骨骼发育和疾病期间Wnt途径组分的需求和关键作用。
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.
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