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Role of wingless tail signaling pathway in osteoporosis: an update of current knowledge

Anastasilakis, Athanasios D.; Polyzos, Stergios A.; Toulis, Konstantinos A.

Current Opinion in Endocrinology & Diabetes and Obesity: December 2011 - Volume 18 - Issue 6 - p 383–388
doi: 10.1097/MED.0b013e32834afff2
Parathyroids, bone and mineral metabolism: Edited by Vin Tangpricha

Purpose of review Wingless 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 findings New insights into the mechanisms regulating Wnt/β-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.

Summary Although 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.

aDepartment of Endocrinology, 424 General Military Hospital

bSecond Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece

Correspondence to Dr Athanasios D. Anastasilakis, Soulini 4, 566 25 Sykies, Greece Tel: +30 2310 639 027; fax: +30 2310 839 900; e-mail:

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.