Genetic studies have been instrumental in the field of orthopaedics for finding tools to improve the standard management of fractures and delayed unions. The Wnt signaling pathway that is crucial for development and maintenance of many organs also has a very promising pathway for enhancement of bone regeneration. The Wnt pathway has been shown to have a direct effect on stem cells during bone regeneration, making Wnt a potential target to stimulate bone repair after trauma. A more complete view of how Wnt influences animal bone regeneration has slowly come to light. This review article provides an overview of studies done investigating the modulation of the canonical Wnt pathway in animal bone regeneration models. This not only includes a summary of the recent work done elucidating the roles of Wnt and β-catenin in fracture healing, but also the results of thirty transgenic studies, and thirty-eight pharmacological studies. Finally, we discuss the discontinuation of sclerostin clinical trials, ongoing clinical trials with lithium, the results of Dkk antibody clinical trials, the shift into combination therapies and the future opportunities to enhance bone repair and regeneration through the modulation of the Wnt signaling pathway.
Keywords: BMP; Bone; DKK1; Fracture healing; Glycogen synthase kinase 3β; PTH; SOST; Sclerostin; Wnt signaling; β-catenin.
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