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Cited by 892

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 access
van Bezooijen, Rutger L., Roelen, Bernard A.J., Visser, Annemieke, van der Wee-Pals, Lianne, de Wilt, Edwin, Karperien, Marcel, Hamersma, Herman, Papapoulos, Socrates E., ten Dijke, Peter, Löwik, Clemens W.G.M.·2004·The Journal of Experimental Medicine

Abstract

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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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
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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CoChat. (2026). Citation check: Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist. https://app.cochat.ai/papers/10.1084/jem.20031454
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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.