The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
VEGFA is necessary for chondrocyte survival during bone development
Open accessAbstract
To directly examine the role of vascular endothelial growth factor (VEGFA)in cartilage development, we conditionally knocked out Vegfa in chondrocytes, using the Col2a1 promoter to drive expression of Cre recombinase. Our study of Vegfa conditional knockout (CKO) mice provides new in-vivo evidence for two important functions of VEGFA in bone formation. First, VEGFA plays a significant role in both early and late stages of cartilage vascularization, since Vegfa CKO mice showed delayed invasion of blood vessels into primary ossification centers and delayed removal of terminal hypertrophic chondrocytes. Second, VEGFA is crucial for chondrocyte survival, since massive cell death was seen in joint and epiphyseal regions of Vegfa CKO endochondral bones. Chondrocytes in these regions were found to upregulate expression of Vegfa in wild-type mice at the time when massive cell death occurred in the Vegfa CKO mice. The expression of the VEGFA receptors Npr1 and Npr2 in epiphyseal chondrocytes and lack of blood vessel reduction in the vicinity of the cartilaginous elements in the Vegfa CKO mice raise the possibility that the observed cell death is the result of a direct involvement of VEGFA in chondrocyte survival. Interestingly, the extensive cell death seen in Vegfa CKO null bones had a striking similarity to the cell death phenotype observed when hypoxia-inducible factor 1α (Hif1a)expression was abolished in developing cartilage. This similarity of cell death phenotypes and the deficient VEGFA production in Hif1a null epiphyseal chondrocytes demonstrate that HIF1α and VEGFA are components of a key pathway to support chondrocyte survival during embryonic bone development.
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.
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
The biology of VEGF and its receptors
Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003) · Nature Medicine · doi:10.1038/nm0603-669 · Cited by 9,591
Self-citationTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1×
“…Semenza and Wang, 1992; Wang and Semenza, 1993; Wang and Semenza, 1995; Zelzer et al., 1998); the tumorsuppressor protein von Hippel-Lindau (VHL) protein is a key element in this regulation (Bruick and McKnight, 2001; Ivan et al., 2001; Jaakkola et al., 2001; Masson et al., 2001; Yu et al., 2001).”
BackgroundThe Biology of Vascular Endothelial Growth Factor
Ferrara, N., & Davis-Smyth, T. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.1.0287 · Cited by 4,330
Self-citationSemenza, G. L., & Wang, G. L. (1992) · Molecular and Cellular Biology · doi:10.1128/mcb.12.12.5447 · Cited by 2,617
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
Purification and Characterization of Hypoxia-inducible Factor 1
Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,073
Gerber, H.-P., McMurtrey, A., Kowalski, J., Yan, M., Keyt, B. A., Dixit, V., & Ferrara, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30336 · Cited by 1,981
Self-citationMolecular and Biological Properties of the Vascular Endothelial Growth Factor Family of Proteins
FERRARA, N., HOUCK, K., JAKEMAN, L., & LEUNG, D. W. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-1-18 · Cited by 1,655
Self-citationBenjamin, L. E., Golijanin, D., Itin, A., Pode, D., & Keshet, E. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5028 · Cited by 1,241
Park, J. E., Keller, G. A., & Ferrara, N. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.12.1317 · Cited by 1,122
Self-citationInduction of Pancreatic Differentiation by Signals from Blood Vessels
Lammert, E., Cleaver, O., & Melton, D. (2001) · Science · doi:10.1126/science.1064344 · Cited by 1,050
Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · cited 2×
“…Semenza and Wang, 1992; Wang and Semenza, 1993; Wang and Semenza, 1995; Zelzer et al., 1998); the tumorsuppressor protein von Hippel-Lindau (VHL) protein is a key element in this regulation (Bruick and McKnight, 2001; Ivan et al., 2001; Jaakkola et al., 2001; Masson et al., 2001; Yu et al., 2001).”
BackgroundExpression of Cre recombinase in the developing mouse limb bud driven by a Prxl enhancer
Logan, M., Martin, J. F., Nagy, A., Lobe, C., Olson, E. N., & Tabin, C. J. (2002) · genesis · doi:10.1002/gene.10092 · Cited by 1,005
Gerber, H.-P., Dixit, V., & Ferrara, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.13313 · Cited by 981
Self-citationVEGF is required for growth and survival in neonatal mice
Gerber, H.-P., Hillan, K. J., Ryan, A. M., Kowalski, J., Keller, G.-A., Rangell, L., Wright, B. D., Radtke, F., Aguet, M., & Ferrara, N. (1999) · Development · doi:10.1242/dev.126.6.1149 · Cited by 915
Self-citationLiver Organogenesis Promoted by Endothelial Cells Prior to Vascular Function
Matsumoto, K., Yoshitomi, H., Rossant, J., & Zaret, K. S. (2001) · Science · doi:10.1126/science.1063889 · Cited by 875
Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia.
Wang, G. L., & Semenza, G. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80571-7 · Cited by 862
Olsen, B. R., Reginato, A. M., & Wang, W. (2000) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.16.1.191 · Cited by 822
Self-citationHypoxia in cartilage: HIF-1α is essential for chondrocyte growth arrest and survival
Schipani, E., Ryan, H. E., Didrickson, S., Kobayashi, T., Knight, M., & Johnson, R. S. (2001) · Genes & Development · doi:10.1101/gad.934301 · Cited by 806
Self-citationHIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796
Ivkovic, S., Yoon, B. S., Popoff, S. N., Safadi, F. F., Libuda, D. E., Stephenson, R. C., Daluiski, A., & Lyons, K. M. (2003) · Development · doi:10.1242/dev.00505 · Cited by 713
VEGF regulates haematopoietic stem cell survival by an internal autocrine loop mechanism
Gerber, H.-P., Malik, A. K., Solar, G. P., Sherman, D., Liang, X. H., Meng, G., Hong, K., Marsters, J. C., & Ferrara, N. (2002) · Nature · doi:10.1038/nature00821 · Cited by 706
Self-citationCarmeliet, P., Ng, Y.-S., Nuyens, D., Theilmeier, G., Brusselmans, K., Cornelissen, I., Ehler, E., Kakkar, V. V., Stalmans, I., Mattot, V., et al. (1999) · Nature Medicine · doi:10.1038/8379 · Cited by 679
Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.
Feldser, D. M., Agani, F. H., Iyer, N. V., Pak, B. J., Ferreira, G., & Semenza, G. L. (1999) · PubMed · Cited by 638
(2003) · PubMed · Cited by 624
Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S
McLeod, M. J. (1980) · Teratology · doi:10.1002/tera.1420220306 · Cited by 613
Insulin induces transcription of target genes through the hypoxia-inducible factor HIF-1alpha /ARNT
Zelzer, E. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5085 · Cited by 575
Self-citationDeckers, M. M. L. (2000) · Endocrinology · doi:10.1210/en.141.5.1667 · Cited by 552
Endothelial signaling during development
Cleaver, O., & Melton, D. A. (2003) · Nature Medicine · doi:10.1038/nm0603-661 · Cited by 517
Dual 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
Maes, C., Carmeliet, P., Moermans, K., Stockmans, I., Smets, N., Collen, D., Bouillon, R., & Carmeliet, G. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(01)00601-3 · Cited by 456
Skeletal defects in VEGF120/120 mice reveal multiple roles for VEGF in skeletogenesis
Zelzer, E., McLean, W., Ng, Y.-S., Fukai, N., Reginato, A. M., Lovejoy, S., D’Amore, P. A., & Olsen, B. R. (2002) · Development · doi:10.1242/dev.129.8.1893 · Cited by 445
Self-citationBachelder, R. E., Crago, A. M., Chung, J., Wendt, M. A., Shaw, L. M., Robinson, G. S., & Mercurio, A. M. (2001) · PubMed · Cited by 438
Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.6.2423 · Cited by 411
The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis
Hall, B. K., & Miyake, T. (1992) · Anatomy and Embryology · doi:10.1007/bf00174948 · Cited by 375
Shima, D. T., Adamis, A. P., Ferrara, N., Yeo, K.-T., Yeo, T.-K., Allende, R., Folkman, J., & D’Amore, P. A. (1995) · Molecular Medicine · doi:10.1007/bf03401566 · Cited by 352
Self-citationTissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2
Zelzer, E., Glotzer, D. J., Hartmann, C., Thomas, D., Fukai, N., Soker, S., & Olsen, B. R. (2001) · Mechanisms of Development · doi:10.1016/s0925-4773(01)00428-2 · Cited by 339
Self-citationThe Mouse Gene for Vascular Endothelial Growth Factor
Shima, D. T., Kuroki, M., Deutsch, U., Ng, Y.-S., Adamis, A. P., & D'Amore, P. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3877 · Cited by 327
The genetic transformation of bone biology
Karsenty, G. (1999) · Genes & Development · doi:10.1101/gad.13.23.3037 · Cited by 312
Vasculotropin/Vascular Endothelial Growth Factor Induces Differentiation in Cultured Osteoblasts
Midy, V., & Plouet, J. (1994) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1994.1240 · Cited by 285
HIF-1α controls extracellular matrix synthesis by epiphyseal chondrocytes
Pfander, D., Cramer, T., Schipani, E., & Johnson, R. S. (2003) · Journal of Cell Science · doi:10.1242/jcs.00385 · Cited by 258
Self-citationWang, L., Zeng, H., Wang, P., Soker, S., & Mukhopadhyay, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m310047200 · Cited by 211
Haigh, J. J., Gerber, H.-P., Ferrara, N., & Wagner, E. F. (2000) · Development · doi:10.1242/dev.127.7.1445 · Cited by 192
Self-citationFoster, R. R., Hole, R., Anderson, K., Satchell, S. C., Coward, R. J., Mathieson, P. W., Gillatt, D. A., Saleem, M. A., Bates, D. O., & Harper, S. J. (2003) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00276.2002 · Cited by 176
Pfander, D., Kobayashi, T., Knight, M. C., Zelzer, E., Chan, D. A., Olsen, B. R., Giaccia, A. J., Johnson, R. S., Haase, V. H., & Schipani, E. (2004) · Development · doi:10.1242/dev.01138 · Cited by 128
Self-citation
Cited by
Matrix-embedded cells control osteoclast formation
Xiong, J., Onal, M., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & O'Brien, C. A. (2011) · Nature Medicine · doi:10.1038/nm.2448 · Cited by 1,304
Endothelial cells and VEGF in vascular development
Coultas, L., Chawengsaksophak, K., & Rossant, J. (2005) · Nature · doi:10.1038/nature04479 · Cited by 1,016
The roles of vascular endothelial growth factor in bone repair and regeneration
Hu, K., & Olsen, B. R. (2016) · Bone · doi:10.1016/j.bone.2016.06.013 · Cited by 678
Self-citationOsteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair
Hu, K., & Olsen, B. R. (2016) · Journal of Clinical Investigation · doi:10.1172/jci82585 · Cited by 668
Self-citationSaito, T., Fukai, A., Mabuchi, A., Ikeda, T., Yano, F., Ohba, S., Nishida, N., Akune, T., Yoshimura, N., Nakagawa, T., et al. (2010) · Nature Medicine · doi:10.1038/nm.2146 · Cited by 532
Metadata
- Authors
- Zelzer, E., Mamluk, R., Ferrara, N., Johnson, R. S., Schipani, E., & Olsen, B. R.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2004-05-01
- Volume
- 131
- Issue
- 9
- Pages
- 2161-2171
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2086964102
- Cited by
- 401
- References
- 48
- FWCI
- 9.20
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.