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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
The Journal of cell biology | 2002

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.

Pubmed ID: 11956231

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Associated grants

  • Agency: NIDCR NIH HHS, United States
    Id: DE11290
  • Agency: NHLBI NIH HHS, United States
    Id: HL16512
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL051586
  • Agency: NHLBI NIH HHS, United States
    Id: HL51586
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL016512
  • Agency: NIDDK NIH HHS, United States
    Id: DK58882
  • Agency: NIAMS NIH HHS, United States
    Id: P01 AR042919
  • Agency: NIDCR NIH HHS, United States
    Id: R01 DE011290
  • Agency: NIAMS NIH HHS, United States
    Id: AR42919

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COS-7 (tool)

RRID:CVCL_0224

Cell line COS-7 is a Transformed cell line with a species of origin Chlorocebus aethiops (Green monkey)

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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