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Lrp5 functions in bone to regulate bone mass.

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.

Pubmed ID: 21602802

Authors

  • Cui Y
  • Niziolek PJ
  • MacDonald BT
  • Zylstra CR
  • Alenina N
  • Robinson DR
  • Zhong Z
  • Matthes S
  • Jacobsen CM
  • Conlon RA
  • Brommage R
  • Liu Q
  • Mseeh F
  • Powell DR
  • Yang QM
  • Zambrowicz B
  • Gerrits H
  • Gossen JA
  • He X
  • Bader M
  • Williams BO
  • Warman ML
  • Robling AG

Journal

Nature medicine

Publication Data

June 7, 2011

Associated Grants

  • Agency: NIAMS NIH HHS, Id: AR053293
  • Agency: NIAMS NIH HHS, Id: AR53237
  • Agency: NIAMS NIH HHS, Id: R01 AR053293
  • Agency: NIAMS NIH HHS, Id: R01 AR053293-01A2
  • Agency: NIAMS NIH HHS, Id: R01 AR053293-02
  • Agency: NIAMS NIH HHS, Id: R01 AR053293-03
  • Agency: NIAMS NIH HHS, Id: R01 AR053293-04
  • Agency: NIAMS NIH HHS, Id: R01 AR053293-05
  • Agency: NCRR NIH HHS, Id: UL 1RR025761-02
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alleles
  • Animals
  • Bone Density
  • Bone and Bones
  • Female
  • Gene Knock-In Techniques
  • Gene Knockout Techniques
  • Genotype
  • LDL-Receptor Related Proteins
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Osteocytes
  • Serotonin
  • Spine
  • Tryptophan Hydroxylase