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Lrp5 functions in bone to regulate bone mass

Official URL:https://doi.org/10.1038/nm.2388
PubMed:View item in PubMed
Creators Name:Cui, Y. and Niziolek, P.J. and Macdonald, B.T. and Zylstra, C.R. and Alenina, N. and Robinson, D.R. and Zhong, Z. and Matthes, S. and Jacobsen, C.M. and Conlon, R.A. and Brommage, R. and Liu, Q. and Mseeh, F. and Powell, D.R. and Yang, Q.M. and Zambrowicz, B. and Gerrits, H. and Gossen, J.A. and He, X. and Bader, M. and Williams, B.O. and Warman, M.L. and Robling, A.G.
Journal Title:Nature Medicine
Journal Abbreviation:Nat Med
Volume:17
Number:6
Page Range:684-691
Date:June 2011
Keywords:Alleles, Bone Density, Bone and Bones, Gene Knock-In Techniques, Gene Knockout Techniques, Genotype, LDL-Receptor Related Proteins, Osteocytes, Serotonin, Spine, Tryptophan Hydroxylase, Animals, Mice
Abstract:The human skeleton is affected by mutations in low-density lipoprotein receptor-related protein 5 (LRP5). To understand how LRP5 influences bone properties, we generated mice with osteocyte-specific expression of inducible Lrp5 mutations that cause high and low bone mass phenotypes in humans. We found that bone properties in these mice were comparable to bone properties in mice with inherited mutations. We also induced an Lrp5 mutation in cells that form the appendicular skeleton but not in cells that form the axial skeleton; we observed that bone properties were altered in the limb but not in the spine. These data indicate that Lrp5 signaling functions locally, and they suggest that increasing LRP5 signaling in mature bone cells may be a strategy for treating human disorders associated with low bone mass, such as osteoporosis.
ISSN:1078-8956
Publisher:Nature Publishing Group (U.S.A.)
Item Type:Article

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