The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650020617 · Cited by 5,344
Bone Histomorphometry : Standardization of Nomenclature, Symbols, and Units
PARFITT, A. M., Drezner, M. K., Glorieux, F. H., Kanis, J. А., Malluche, H. H., Meunier, P. J., Ott, S. M., & Recker, R. R. (1987) · Journal of Bone and Mineral Research · Cited by 3,258
Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon Carcinoma
Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., Vogelstein, B., & Clevers, H. (1997) · Science · doi:10.1126/science.275.5307.1784 · Cited by 2,905
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00571-2 · Cited by 2,235
MECHANISMS OF WNT SIGNALING IN DEVELOPMENT
Wodarz, A., & Nusse, R. (1998) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.14.1.59 · Cited by 2,030
The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain
McMahon, A. P., & Bradley, A. (1990) · Cell · doi:10.1016/0092-8674(90)90385-r · Cited by 1,540
A new member of the frizzled family from Drosophila functions as a Wingless receptor
Bhanot, P., van den Brink, M. R. M., Samos, C. H., Hsieh, J.-C., Wang, Y., Macke, J. P., Andrew, D. J., Nathans, J., & Nusse, R. (1996) · Nature · doi:10.1038/382225a0 · Cited by 1,504
Little, R. D., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., Zweier, S., Braunschweiger, K., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/338450 · Cited by 1,282
Female development in mammals is regulated by Wnt-4 signalling
Vainio, S. J., Heikkilä, M. M., Kispert, A., Chin, N., & McMahon, A. P. (1999) · Nature · doi:10.1038/17068 · Cited by 1,263
LDL-receptor-related proteins in Wnt signal transduction
Tamai, K., Semenov, M., Kato, Y., Spokony, R., Liu, C., Katsuyama, Y., Hess, F., Saint-Jeannet, J.-P., & He, X. (2000) · Nature · doi:10.1038/35035117 · Cited by 1,128
An LDL-receptor-related protein mediates Wnt signalling in mice
Pinson, K. I., Brennan, J., Monkley, S. J., Avery, B. J., & Skarnes, W. C. (2000) · Nature · doi:10.1038/35035124 · Cited by 1,086
LRP: a multifunctional scavenger and signaling receptor
Herz, J., & Strickland, D. K. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13992 · Cited by 908
LRP: a multifunctional scavenger and signaling receptor
Herz, J., & Strickland, D. K. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200113992 · Cited by 908
Mao, J., Wang, J., Liu, B., Pan, W., Farr, G. H., Flynn, C., Yuan, H., Takada, S., Kimelman, D., Li, L., et al. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00224-6 · Cited by 839 · cited 3×
“Wnt proteins and postnatal bone formation Cell culture analyses have shown that LRP5 acts as a coreceptor for Wnt proteins (Mao et al., 2001).”
BackgroundInfluentialA Cbfa1-dependent genetic pathway controls bone formation beyond embryonic developmentPreprint
Ducy, P. F., Starbuck, M., Priemel, M., Shen, J., Pinero, G. J., Geoffroy, V., Amling, M., & Karsenty, G. (1999) · Genes & Development · doi:10.1101/gad.13.8.1025 · Cited by 772
Self-citationNew aspects of Wnt signaling pathways in higher vertebrates
Huelsken, J., & Birchmeier, W. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00231-8 · Cited by 561
Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skinPreprint
Merrill, B. J., Gat, U., DasGupta, R., & Fuchs, E. V. (2001) · Genes & Development · doi:10.1101/gad.891401 · Cited by 559
Hartmann, C., & Tabin, C. J. (2001) · Cell · doi:10.1016/s0092-8674(01)00222-7 · Cited by 487
Self-citationDual roles of Wnt signaling during chondrogenesis in the chicken limb
Hartmann, C., & Tabin, C. J. (2000) · Development · doi:10.1242/dev.127.14.3141 · Cited by 472
Self-citationTHE MAMMALIAN LOW-DENSITY LIPOPROTEIN RECEPTOR FAMILY
Hussain, M. M., Strickland, D. K., & Bakillah, A. (1999) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.19.1.141 · Cited by 390
Macrophages are required for cell death and tissue remodeling in the developing mouse eye
Lang, R. A., & Bishop, J. M. (1993) · Cell · doi:10.1016/0092-8674(93)80047-i · Cited by 366
Self-citationSexually dimorphic development of the mammalian reproductive tract requires Wnt-7a
Parr, B. A., & McMahon, A. P. (1998) · Nature · doi:10.1038/27221 · Cited by 358
The genetic transformation of bone biologyPreprint
Karsenty, G. (1999) · Genes & Development · doi:10.1101/gad.13.23.3037 · Cited by 311
Self-citationLimb development in mouse embryos. I. Analysis of teratogenic effects of retinoic acid
Kochhar, D. M. (1973) · Teratology · doi:10.1002/tera.1420070310 · Cited by 288
Dynamic histomorphometry of alveolar bone remodeling in the adult rat
Vignery, A., & Baron, R. (1980) · The Anatomical Record · doi:10.1002/ar.1091960210 · Cited by 260
Cytoskeletal reorganization by soluble Wnt‐3a protein signalling
Shibamoto, Higano, K., Takada, R., Ito, F., Takeichi, M., & Takada, S. (1998) · Genes to Cells · doi:10.1046/j.1365-2443.1998.00221.x · Cited by 251
Gong, Y., Vikkula, M., Boon, L. M., Liu, J., Beighton, P., Ramesar, R., Peltonen, L., Somer, H., Hirose, T., Dallapiccola, B., et al. (1996) · PubMed Central · Cited by 245
Apolipoprotein E receptors: linking brain development and alzheimer's disease
Herz, J., & Beffert, U. (2000) · Nature reviews. Neuroscience · doi:10.1038/35036221 · Cited by 224
Cloning of a novel member of the low-density lipoprotein receptor family
Hey, P. J., Twells, R. C. J., Phillips, M. S., Nakagawa, Y., Brown, S. D., Kawaguchi, Y., Cox, R., Xie, G., Dugan, V., Hammond, H. A., et al. (1998) · Gene · doi:10.1016/s0378-1119(98)00311-4 · Cited by 222
Regression of the hyaloid vessels and pupillary membrane of the mouse
Ito, M., & Yoshioka, M. (1999) · Anatomy and Embryology · doi:10.1007/s004290050289 · Cited by 217
Yamazaki, H., Bujo, H., Kusunoki, J., Seimiya, K., Kanaki, T., Morisaki, N., Schneider, W. J., & Saitō, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.40.24761 · Cited by 205
Brown, S. D., Twells, R. C. J., Hey, P. J., Cox, R. D., Levy, E. R., Soderman, A. R., Metzker, M. L., Caskey, C. T., Todd, J. A., & Hess, J. F. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9061 · Cited by 176
Apoptosis during macrophage-dependent ocular tissue remodelling
Lang, R. A., Lustig, M., Francois, F., Sellinger, M., & Plesken, H. (1994) · Development · doi:10.1242/dev.120.12.3395 · Cited by 165
Self-citationThe low-density lipoprotein receptor gene family: multiple roles in lipid metabolism
Willnow, T. E. (1999) · Journal of Molecular Medicine · doi:10.1007/s001090050356 · Cited by 165
Macrophages induce apoptosis in normal cells in vivo
Diez‐Roux, G., & Lang, R. A. (1997) · Development · doi:10.1242/dev.124.18.3633 · Cited by 153
Self-citationMeeson, A. P., Palmer, M. A. J., Calfon, M. A., & Lang, R. A. (1996) · Development · doi:10.1242/dev.122.12.3929 · Cited by 139
Self-citationNegative Feedback Mechanisms and Their Roles during Pattern Formation
Perrimon, N., & McMahon, A. P. (1999) · Cell · doi:10.1016/s0092-8674(00)80710-2 · Cited by 130
Kim, D.-H., Inagaki, Y., Suzuki, T., Ioka, R. X., Yoshioka, S. Z., Magoori, K., Kang, M.-J., Cho, Y., Nakano, A. Z., Liu, Q., et al. (1998) · Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022223 · Cited by 99
Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege
Lang, R. A. (1997) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400211 · Cited by 77
Self-citationYu, D. L., Lathrop, W. F., Weaver, D. R., Qiu, Q., Cini, J. K., Bertolini, D. R., & Chen, D. J. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9545 · Cited by 73
Determinants of peak bone mass
Johnston, C. C., & Slemenda, C. W. (1993) · Osteoporosis International · doi:10.1007/bf01621864 · Cited by 66
Figueroa, D. J., Hess, J. F., Ky, B., Brown, S. D., Sandig, V., Hermanowski‐Vosatka, A., Twells, R. C. J., Todd, J. A., & Austin, C. P. (2000) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540004801006 · Cited by 64
Tomita, Y., Kim, D. H., Magoori, K., Fujino, T., & Yamamoto, T. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022180 · Cited by 53
Ishii, H., Kim, D.-H., Fujita, T., Endo, Y., Saeki, S., & Yamamoto, T. (1998) · Genomics · doi:10.1006/geno.1998.5339 · Cited by 46
Staining of the calcification front in human bone using contrasting fluorochromes in vitro.
Aaron, J. E., Makins, N. B., Francis, R. M., & Peacock, M. (1984) · Journal of Histochemistry & Cytochemistry · doi:10.1177/32.12.6209330 · Cited by 38
Osteoporosis‐pseudoglioma or osteogenesis imperfecta?
Superti‐Furga, A., Steinmann, B., & Perfumo, F. (1986) · Clinical Genetics · doi:10.1111/j.1399-0004.1986.tb01249.x · Cited by 12
Flagged first, then by citations
Research works printed but not linked: 8
- 1996, Am. J. Hum. Genet., 59, 146
- 2001, Curr. Opin. Genet. Dev., 5, 543
- 1993, Osteoporos. Int., 1, S54
- 1987, J. Bone Miner. Res., 6, 595
- 1998, Nature., 95, 707
- 1998, Cell., 97, 707
- 1986, Clin. Genet., 2, 185
- 1999, J. Mol. Med., 77, 306, 10.1007/s001090050356 · DOI
Cited by
Sorted by citations
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568
Wnt/β-catenin signaling and disease
Clevers, H., & Nusse, R. (2012) · Cell · doi:10.1016/j.cell.2012.05.012 · Cited by 5,554
Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities
Liu, J., Xiao, Q., Xiao, J., Niu, C., Li, Y., Zhang, X., Zhou, Z., Shu, G., & Yin, G. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00762-6 · Cited by 2,519
WNT signaling in bone homeostasis and disease: From human mutations to treatments
Baron, R., & Kneissel, M. (2013) · Nature Medicine · doi:10.1038/nm.3074 · Cited by 2,093
Day, T. F., Guo, X., Garrett-Beal, L., & Yang, Y. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.03.016 · Cited by 1,616
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
