Cited by 1,086Bone Metabolism and DiseasesWnt/β-catenin signaling in development and cancerBone health and osteoporosis research

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

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Kato, Masaki, Patel, Millan S., Levasseur, Regis, Lobov, Ivan, Chang, Benny H.-J., Glass, Donald A., Hartmann, Christine, Li, Lan, Hwang, Tae-Ho, Brayton, Cory F., Lang, Richard A., Karsenty, Gerard, Chan, Lawrence·2002·The Journal of Cell Biology

DOI 10.1083/jcb.200201089PMC PMC2199263

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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.

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Authors: Kato, M., Patel, M. S., Levasseur, R., Lobov, I., Chang, B. H.-J., Glass, D. A., Hartmann, C., Li, L., Hwang, T.-H., Brayton, C. F., Lang, R. A., Karsenty, G., & Chan, L.
Affiliations: Baylor College of Medicine (US)
2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
University of Cincinnati (US)
Harvard University (US)
ORCID: Kato, Masaki
Patel, Millan S.
Lobov, Ivan
Chang, Benny H.-J.
Glass, Donald A.
Hartmann, Christine
Hwang, Tae-Ho
Brayton, Cory F.
Lang, Richard A.
Chan, Lawrence
Venue: The Journal of Cell Biology
Publisher: Rockefeller University Press
Published: 2002-04-15
Volume: 157
Issue: 2
Pages: 303-314
ISSN: 0021-9525 (ISSN-L)
1540-8140
DOI: 10.1083/jcb.200201089
PMC: PMC2199263
OpenAlex: W2116610925
Cited by: 1,086
References: 46
Citations by year: 2026: 8 · 2025: 10 · 2024: 18 · 2023: 13 · 2022: 21 · 2021: 24 · 2020: 33 · 2019: 27 · 2018: 26 · 2017: 40 · 2016: 27 · 2015: 39 · 2014: 56 · 2013: 65 · 2012: 61
FWCI: 22.08
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Cell Biology (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Funders: March of Dimes Foundation
Universiteit Utrecht
National Institutes of Health (5r01dk058882-03, AR42919)
Canadian Institutes of Health Research
National Heart, Lung, and Blood Institute (HL16512, R01HL016512, HL-51586, R01HL051586)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 58882)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (P01AR042919, AR42919)
National Institute of Dental and Craniofacial Research (DE11290, R01DE011290)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: LRP5, Wnt signaling, osteoblast proliferation, osteopenia, vascular regression, endothelial cell apoptosis, macrophages, osteoporosis-pseudoglioma syndrome, bone formation, postnatal development
MeSH terms: Animals, Bone and Bones, Bone Development, Bone Diseases, Metabolic, Calcium, Cell Division, Eye, Eye Abnormalities, Immunohistochemistry, Macrophages, Neoplasm Proteins, Organ Size, Osteoblasts, Phenotype, Proto-Oncogene Proteins, Receptors, LDL, Transcription Factors, Signal Transduction, Mutagenesis, Site-Directed, Apoptosis, Mice, Knockout, Gene Expression Regulation, Developmental, In Situ Nick-End Labeling, LDL-Receptor Related Proteins, Zebrafish Proteins, Core Binding Factor Alpha 1 Subunit, Wnt Proteins, Mice, Low Density Lipoprotein Receptor-Related Protein-5

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

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