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

Journal of Cell Biology - Tập 157 Số 2 - Trang 303-314 - 2002
Masaki Kato1, Millan S. Patel2, Régis Levasseur2, Ivan B. Lobov3, Benny Hung‐Junn Chang1, Donald A. Glass2, Christine Hartmann4, Lan Li1, Tae-Ho Hwang1, Cory Brayton5, Richard A. Lang3, Gérard Karsenty2, Lawrence Chan1
11Department of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030
22Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
34Division of Developmental Biology, Department of Ophthalmology, Children's Hospital Research Foundation, University of Cincinnati, Cincinnati, OH 45229
45Department of Genetics, Harvard Medical School, Boston, MA 02115
53Department Pathology, Baylor College of Medicine, Houston, TX 77030

Tóm tắt

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.

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Thông tin xuất bản

Journal of Cell Biology

Tập 157 Số 2

303-314

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