Generic placeholder image

Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

The Therapeutic Potential of the Wnt Signaling Pathway in Bone Disorders

Author(s): Liang Chen, Tong-Chuan He, Rex C. Haydon, Hue H. Luu, Russell R. Reid, Zhong-Liang Deng, Jiayi Huang, Xiaoji Luo, Jinyong Luo, Yuxi Su, Yang Bi, Guo-Wei Zuo, Eric R. Wagner, Bai-Cheng He, Ke Yang, Farbod Rastegar, Stephanie H. Kim, Jian-Li Gao, Yanhong Gao, Enyi Huang, Qiong Shi, Qing Luo, Bing-Qiang Zhang and Gaohui Zhu

Volume 4, Issue 1, 2011

Page: [14 - 25] Pages: 12

DOI: 10.2174/1874467211104010014

Price: $65


The Wnt pathway plays a critical role in development and differentiation of many tissues, such as the gut, hair follicles, and bone. Increasing evidence indicates that Wnts may function as key regulators in osteogenic differentiation of mesenchymal stem cells and bone formation. Conversely, aberrant Wnt signaling is associated with many osteogenic pathologies. For example, genetic alterations in the Wnt signaling pathway lead to osteoporosis and osteopenia, while inactivating mutations of Wnt inhibitors result in a hyperostotic skeleton with increased bone mineral density. Hyperparathyroidism causes osteopenia via induction of the Wnt signaling pathway. Lithium, often used to treat bipolar disorder, blocks a Wnt antagonist, decreasing the patient's risk of fractures. Thus, manipulating the Wnt pathway may offer plenty therapeutic opportunities in treating bone disorders. In fact, induction of the Wnt signaling pathway or inhibition of Wnt antagonists has shown promise in treating bone metabolic disorders, including osteoporosis. For example, antibodies targeting the Wnt inhibitor Sclerostin lead to increased bone mineral density in post-menopausal women. However, such therapies targeting the Wnt pathway are not without risk, as genetic alternations may lead to over-activation of Wnt/β- catenin and its association with many tumors. It is conceivable that targeting Wnt inhibitors may predispose the individuals to tumorigenic phenotypes, at least in bone. Here, we review the roles of Wnt signaling in bone metabolic and pathologic processes, as well as the therapeutic potential for targeting Wnt pathway and its associated risks in bone diseases.

Keywords: Wnt, osteoporosis, sclerostin, catenin, osteogenesis, fracture, osteogenic differentiation, LRP5/6, osteopenia, post-menopausal, cell proliferation, apoptosis, tumorigenesis, FAP, glycoproteins, Frz, stabilization, translocation, GSK3, transcription, c-Myc, cyclin D1, PPAR, APC, PKC, Elk-1, CaCN, NF-AT, phospholipase c, IP3, Dkk-1, SFRPs, Gleevec, Adipogenesis, transducers, antagonists, WIFs, Krm 1/2, Sost, Krm, T-lymphoid, MSCs, BMPs, Hh, Src/ERK, PI3K/Akt, LRP5, OPPG, mutations, osteblasts, Tcf1, bone mass, phenotypes, SERMs, Antibodies, Axin, DCA, BIO, parathyroid hormone, TUMORIGENIC, osteosarcoma, WIF1

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy