Peptide-based mediated disruption of N-cadherin-LRP5/6 interaction promotes Wnt signaling and bone formation

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Eric HaÿPierre J Marie

Abstract

Wnt signaling plays an important role in skeletal biology and diseases. In osteoblasts, we recently showed that the cell-cell adhesion molecule N-cadherin interacts with the Wnt coreceptors LRP5/6 to regulate osteogenesis. In this study we investigated whether targeting the intracellular domain of N-cadherin that interacts with LRP5/6 may promote Wnt signaling and bone formation. By investigating the molecular interactions between the Wnt coreceptors LRP5/6 and N-cadherin, we identified specific LRP5/6- and N-cadherin-interacting intracellular domains that impact Wnt/β-catenin signaling in murine osteoblasts. We showed that truncated N-cadherin constructs that impair N-cadherin-LRP5/6 interactions promote Wnt/β-catenin signaling and osteoblast differentiation. Based on this finding, we developed a peptide-based approach targeting N-cadherin-LRP5 interaction for promoting Wnt signaling and osteoblast function. We found that a competitor peptide containing the 28 last amino acids of LRP5 disrupts LRP5/6-N-cadherin interaction and thereby enhances Wnt/β-catenin signaling in osteoblasts. We also show that the peptide-mediated disruption of N-cadherin-LRP5/6 interaction increases Wnt/β-catenin signaling and osteoblast function in vi...Continue Reading

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Citations

Jan 15, 2014·BoneKEy Reports·Pierre J Marie, Eric Haÿ
May 10, 2013·Calcified Tissue International·Pierre J MarieRoberto Civitelli
Mar 26, 2014·Journal of Cellular Physiology·Eric HaÿPierre J Marie
Aug 21, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Zhendong Zhong, Bart O Williams
Aug 5, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Leila RevolloRoberto Civitelli
Jul 19, 2014·Trends in Endocrinology and Metabolism : TEM·Pierre J MarieZuzana Saidak
Dec 10, 2014·Cellular and Molecular Life Sciences : CMLS·Pierre J Marie
Oct 11, 2016·Annals of the New York Academy of Sciences·Hailin YangFeng Li
Feb 28, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Francesca FontanaRoberto Civitelli
Mar 6, 2018·The Journal of Clinical Investigation·Beom-Jun KimJung-Min Koh
Dec 6, 2017·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Pierre J Marie, Martine Cohen-Solal
Dec 17, 2017·Pharmacological Reviews·Sébastien FoulquierW Matthijs Blankesteijn
Sep 29, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Salvatore PacificoMaria Paola Costi
Oct 30, 2014·Journal of Medicinal Chemistry·Giuseppe CannazzaMaria Paola Costi

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