The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist
Open accessAbstract
Sclerosteosis, a skeletal disorder characterized by high bone mass due to increased osteoblast activity, is caused by loss of the SOST gene product, sclerostin. The localization in bone and the mechanism of action of sclerostin are not yet known, but it has been hypothesized that it may act as a bone morphogenetic protein (BMP) antagonist. We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483). Although sclerostin shares some of the actions of the BMP antagonist noggin, we show here that it also has actions distinctly different from it. In contrast to noggin, sclerostin did not inhibit basal alkaline phosphatase (ALP) activity in KS483 cells, nor did it antagonize BMP-stimulated ALP activity in mouse C2C12 cells. In addition, sclerostin had no effect on BMP-stimulated Smad phosphorylation and direct transcriptional activation of MSX-2 and BMP response element reporter constructs in KS483 cells. Its unique localization and action on osteoblasts suggest that sclerostin may be the previously proposed osteocyte-derived factor that is transported to osteoblasts at the bone surface and inhibits bone formation.
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Cites
Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)
Balemans, W. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.5.537 · Cited by 1,147
Brunkow, M. E., Gardner, J. C., Van Ness, J., Paeper, B. W., Kovacevich, B. R., Proll, S., Skonier, J. E., Zhao, L., Sabo, P. J., Fu, Y.-H., et al. (2001) · The American Journal of Human Genetics · doi:10.1086/318811 · Cited by 1,011
Self-citationIdentification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease
Balemans, W., Patel, N., Ebeling, M., Van Hul, E., Wuyts, W., Lacza, C., Dioszegi, M., Dikkers, F. G., Hildering, P., Willems, P. J., et al. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.2.91 · Cited by 698
Cited by
Bonewald, L. F. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.320 · Cited by 2,287
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
Cellular and molecular mechanisms of bone remodeling
Raggatt, L. J., & Partridge, N. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.041087 · Cited by 1,402
Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling
Li, X., Zhang, Y., Kang, H., Liu, W., Liu, P., Zhang, J., Harris, S. E., & Wu, D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413274200 · Cited by 1,366
BIOMECHANICAL AND MOLECULAR REGULATION OF BONE REMODELING
Robling, A. G., Castillo, A. B., & Turner, C. H. (2006) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.8.061505.095721 · Cited by 1,343
Metadata
- Authors
- van Bezooijen, R. L., Roelen, B. A. J., Visser, A., van der Wee-Pals, L., de Wilt, E., Karperien, M., Hamersma, H., Papapoulos, S. E., ten Dijke, P., & Löwik, C. W. G. M.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2004-03-15
- Volume
- 199
- Issue
- 6
- Pages
- 805-814
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2108403721
- Cited by
- 892
- References
- 3
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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- van Bezooijen, R. L., Roelen, B. A. J., Visser, A., van der Wee-Pals, L., de Wilt, E., Karperien, M., Hamersma, H., Papapoulos, S. E., ten Dijke, P., & Löwik, C. W. G. M. (2004). Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20031454
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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.