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. Author manuscript; available in PMC: 2018 Feb 5.
Published in final edited form as: Lancet Diabetes Endocrinol. 2017 Jul 7;5(11):898–907. doi: 10.1016/S2213-8587(17)30188-2

Figure 2. Overview of the Wnt signalling pathway—effects of ligands, inhibitors, and targeted therapies.

Figure 2

(A) After binding of Wnt to the LRP5/6 receptor, β-catenin translocates into the nucleus, binds to TCF/LEF transcription factors, and stimulates transcription of osteoblast genes, which results in enhanced bone formation. (B) The endogenous Wnt inhibitors sclerostin and DKK-1 interfere with Wnt signal transduction, resulting in less β-catenin translocation into the nucleus. Osteoblastic functions and bone formation is reduced. (C) Antibodies against sclerostin or DKK-1, or both, neutralise the Wnt inhibitors, thus restoring the scenario of unopposed Wnt signalling as depicted in panel A, which leads to enhanced osteoblastic bone formation. LRP5=low-density lipoprotein receptor-related protein 5. FZD=frizzled. DSH=dishevelled. DKK-1=dickkopf-related protein 1.