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Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor
Open accessAbstract
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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“Given that loss-of-function mutations in the Wnt receptor LRP5 results in low bone mass in both humans (47) and mice (48), the down-regulation of sFRP4, taken together with changes in levels of several Wnt inhibitors, suggests that altered Wnt signaling may play a role in bone loss resulting from exposure to microgravity and that the protective effect of ACVR2B/Fc on microgravity-induced bone loss”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [48]
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“By using co-immunoprecipitation, several group reported that LRP6 can bind Wnt1, Wnt3a and Xenopus Wnt8 (Tamai et al., 2000;Mao et al., 2001;Kato et al., 2002;Itasaki et al., 2003;Liu et al., 2003).”
From Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding (2005) · cites this paper as Kato et al., 2002
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Metadata
- 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
- 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
- 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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