The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
The hypoxia-inducible factor α pathway couples angiogenesis to osteogenesis during skeletal development
Open accessAbstract
Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia-inducible factor alpha (HIF alpha) pathway. Here we provide evidence that HIF alpha promotes angiogenesis and osteogenesis by elevating VEGF levels in osteoblasts. Mice overexpressing HIF alpha in osteoblasts through selective deletion of the von Hippel-Lindau gene (Vhl) expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones. By contrast, mice lacking Hif1a in osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long bones were significantly thinner and less vascularized than those of controls. Loss of Vhl in osteoblasts increased endothelial sprouting from the embryonic metatarsals in vitro but had little effect on osteoblast function in the absence of blood vessels. Mice lacking both Vhl and Hif1a had a bone phenotype intermediate between those of the single mutants, suggesting overlapping functions of HIFs in bone. These studies suggest that activation of the HIF alpha pathway in developing bone increases bone modeling events through cell-nonautonomous mechanisms to coordinate the timing, direction, and degree of new blood vessel formation in bone.
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 tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · cited 1×
“Hypoxia triggers the changes in oxygen-regulated gene expression via the activation of the Per/Arnt/Sim (PAS) subfamily of basic helix-loop-helix (bHLH) transcription factors (2).”
BackgroundDifferential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865
Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis
Karhausen, J., Furuta, G. T., Tomaszewski, J. E., Johnson, R. S., Colgan, S. P., & Haase, V. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421086 · Cited by 655
Self-citationCirculating Osteoblast-Lineage Cells in Humans
Eghbali-Fatourechi, G. Z., Lamsam, J., Fraser, D., Nagel, D., Riggs, B. L., & Khosla, S. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044264 · Cited by 418
Failure to prolyl hydroxylate hypoxia‐inducible factor α phenocopies VHL inactivation in vivo
Kim, W. Y., Safran, M., Buckley, M. R., Ebert, B. L., Glickman, J., Bosenberg, M., Regan, M., & Kaelin, W. G. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601300 · Cited by 235
Cited by
Hypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis
Xie, H., Cui, Z., Wang, L., Xia, Z., Hu, Y., Xian, L., Li, C., Xie, L., Crane, J., Wan, M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3668 · Cited by 951
Self-citationWeidemann, A., & Johnson, R. S. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.12 · Cited by 941
Self-citationThe 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
Mechanical regulation of bone remodeling
Wang, L., You, X., Zhang, L., Zhang, C., & Zou, W. (2022) · Bone Research · doi:10.1038/s41413-022-00190-4 · Cited by 641
Metadata
- Authors
- Wang, Y., Wan, C., Deng, L., Liu, X., Cao, X., Gilbert, S. R., Bouxsein, M. L., Faugere, M.-C., Guldberg, R. E., Gerstenfeld, L. C., Haase, V. H., Johnson, R. S., Schipani, E., & Clemens, T. L.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-06-01
- Volume
- 117
- Issue
- 6
- Pages
- 1616-1626
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2038607522
- Cited by
- 733
- References
- 10
- FWCI
- 13.29
- 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.
