The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
LRP5 Mutations Linked to High Bone Mass Diseases Cause Reduced LRP5 Binding and Inhibition by SOST
Open accessAbstract
The low density lipoprotein (LDL) receptor-related protein 5 (LRP5) is a co-receptor for Wnt proteins and a major regulator in bone homeostasis. Human genetic studies have shown that recessive loss-of-function mutations in LRP5 are linked to osteoporosis, while on the contrary, dominant missense LRP5 mutations are associated with high bone mass (HBM) diseases. All LRP5 HBM mutations are clustered in a single region in the LRP5 extracellular domain and presumably result in elevated Wnt signaling in bone forming cells. Here we show that LRP5 HBM mutant proteins exhibit reduced binding to a secreted bone-specific LRP5 antagonist, SOST, and consequently are more refractory to inhibition by SOST. As loss-of-function mutations in the SOST gene are associated with Sclerosteosis, another disorder of excessive bone growth, our study suggests that the SOST-LRP5 antagonistic interaction plays a central role in bone mass regulation and may represent a nodal point for therapeutic intervention for osteoporosis and other bone diseases.
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Cites
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Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling
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Cited by
Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases
MacDonald, B. T., Tamai, K., & He, X. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.06.016 · Cited by 5,583
Self-citationWnt/β-catenin signaling and disease
Clevers, H., & Nusse, R. (2012) · Cell · doi:10.1016/j.cell.2012.05.012 · Cited by 5,554
Mechanical Stimulation of Bone in Vivo Reduces Osteocyte Expression of Sost/Sclerostin
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Molecular and cellular mechanisms of the anabolic effect of intermittent PTH
Jilka, R. L. (2007) · Bone · doi:10.1016/j.bone.2007.03.017 · Cited by 720
Metadata
- Authors
- Semenov, M. V., & He, X.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 281
- Issue
- 50
- Pages
- 38276-38284
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1998758244
- Cited by
- 222
- References
- 14
- FWCI
- 16.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Semenov, M. V., & He, X. (2006). LRP5 Mutations Linked to High Bone Mass Diseases Cause Reduced LRP5 Binding and Inhibition by SOST. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m609509200
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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).
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