Role of wingless tail signaling pathway in osteoporosis: an update of current knowledge
Role of wingless tail signaling pathway in osteoporosis: an update of current knowledge
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DOI：
10.1097/med.0b013e32834afff2
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发表时间：
2011-12-01
影响因子：
3.2
通讯作者：
Toulis, Konstantinos A.
中科院分区：
文献类型：
--
作者：
Anastasilakis, Athanasios D.;Polyzos, Stergios A.;Toulis, Konstantinos A.
综述目的无翼尾（Wingless tail，Wnt）信号通路对成骨细胞的活化和活动至关重要.本文综述了近年来Wnt信号通路改变在骨质疏松症发病机制、诊断和潜在治疗中的作用，并对Wnt/β-catenin经典通路的调节机制，包括Kremen-2受体、核纤层蛋白A/C蛋白、periostin和pleiotropin在骨生理学中的作用，RUNX-2转录因子级联和Wnt通路之间的串扰，以及单个Wnt配体在骨环境中可能具有独特和不同的使命的概念。营养习惯可能会影响骨骼中的Wnt信号传导。血清sclerostin和dickkopf-1水平可作为骨代谢和疾病的标志物，但需要进一步的标准化方法。最后，讨论了目前抗肿瘤治疗对Wnt信号的影响，以及靶向Wnt信号放大或Wnt拮抗剂减弱的药物的治疗潜力。了解其复杂的病理生理学引起了有前途的骨质疏松症的治疗方法。然而，考虑到Wnt信号传导对许多组织至关重要，新出现的知识应该谨慎地转化为治疗方法。
Purpose of reviewWingless tail (Wnt) pathway is crucial for osteoblast activation and action. This review summarizes the evidence published during the previous year on the emerging role of Wnt signaling alterations in the pathogenesis, diagnosis, and potential therapeutic approaches of osteoporosis.Recent findingsNew insights into the mechanisms regulating Wnt/beta-catenin canonical pathway, including the role of Kremen-2 receptor, lamin A/C protein, periostin, and pleiotropin in bone physiology, the crosstalk between the RUNX-2 transcription-factor cascade and the Wnt pathway, and the concept that individual Wnt ligands may have a unique and distinct mission in bone milieu, are presented. Nutritional habits may affect Wnt signaling in bone. Serum sclerostin and dickkopf-1 levels may serve as markers of bone metabolism and disease, although further standardization methods are required. Finally, the effect of current antiosteoporotic treatments on Wnt signaling is discussed, as well as the therapeutic potential of drugs targeting either Wnt signaling amplification or Wnt antagonists' attenuation.SummaryAlthough Wnt pathway is currently a field of thorough investigation, it is still far from been fully elucidated. Understanding its complex pathophysiology has evoked promising therapeutic approaches for osteoporosis. However, given that Wnt signaling is crucial for many tissues, emerging knowledge should be cautiously translated in therapeutics.