Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor

Masaki Kato, Millan S. Patel, Regis Levasseur, Ivan Lobov, Benny H.J. Chang, Donald A. Glass, Christine Hartmann, Lan Li, Tae Ho Hwang, Cory F. Brayton, Richard A. Lang, Gerard Karsenty, Lawrence Chan

Research output: Contribution to journalArticlepeer-review

893 Citations (Scopus)

Abstract

The low-density lipoprotein receptor-related protein (Lrp)-5 functions as a Wnt coreceptor. Here we show that mice with a targeted disruption of Lrp5 develop a low bone mass phenotype. In vivo and in vitro analyses indicate that this phenotype becomes evident postnatally, and demonstrate that it is secondary to decreased osteoblast proliferation and function in a Cbfa1-independent manner. Lrp5 is expressed in osteoblasts and is required for optimal Wnt signaling in osteoblasts. In addition, Lrp5-deficient mice display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. These results implicate Wnt proteins in the postnatal control of vascular regression and bone formation, two functions affected in many diseases. Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation.

Original languageEnglish
Pages (from-to)303-314
Number of pages12
JournalJournal of Cell Biology
Volume157
Issue number2
DOIs
Publication statusPublished - Apr 15 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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