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SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease

The study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations we...

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Detalles Bibliográficos
Autores principales: Mason, James J., Williams, Bart O.
Formato: Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951123/
https://www.ncbi.nlm.nih.gov/pubmed/20948575
http://dx.doi.org/10.4061/2010/460120
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author Mason, James J.
Williams, Bart O.
author_facet Mason, James J.
Williams, Bart O.
author_sort Mason, James J.
collection PubMed
description The study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations were identified that encoded forms of LRP5 associated with very high bone mass (HBM). HBM patients live to a normal age and do not appear to have increased susceptibility to carcinogenesis or other disease. Thus, devising methods to mimic the molecular consequences of this mutation to treat bone diseases associated with low bone mass is a promising avenue to pursue. Two groups of agents related to putative LRP5/6 functions are under development. One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST). Another group of reagents under development is based on the observation that LRP5 may function to control bone mass by regulating the secretion of serotonin from the enterrochromaffin cells of the duodenum.
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spelling pubmed-29511232010-10-14 SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease Mason, James J. Williams, Bart O. J Osteoporos Review Article The study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations were identified that encoded forms of LRP5 associated with very high bone mass (HBM). HBM patients live to a normal age and do not appear to have increased susceptibility to carcinogenesis or other disease. Thus, devising methods to mimic the molecular consequences of this mutation to treat bone diseases associated with low bone mass is a promising avenue to pursue. Two groups of agents related to putative LRP5/6 functions are under development. One group, the focus of this paper, is based on antagonizing the functions of putative inhibitors of Wnt signaling, Dickkopf-1 (DKK1), and Sclerostin (SOST). Another group of reagents under development is based on the observation that LRP5 may function to control bone mass by regulating the secretion of serotonin from the enterrochromaffin cells of the duodenum. SAGE-Hindawi Access to Research 2010-07-01 /pmc/articles/PMC2951123/ /pubmed/20948575 http://dx.doi.org/10.4061/2010/460120 Text en Copyright © 2010 J. J. Mason and B. O. Williams. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Mason, James J.
Williams, Bart O.
SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
title SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
title_full SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
title_fullStr SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
title_full_unstemmed SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
title_short SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease
title_sort sost and dkk: antagonists of lrp family signaling as targets for treating bone disease
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951123/
https://www.ncbi.nlm.nih.gov/pubmed/20948575
http://dx.doi.org/10.4061/2010/460120
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