The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength
Open accessAbstract
Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone. Materials and Methods: Gene targeting was used to inactivate SOST and generate a line of SOST KO mice. Radiography, densitometry, μCT, histomorphometry, and mechanical testing were used to characterize the impact of sclerostin deficiency on bone in male and female mice. Comparisons were made between same sex KO and wildtype (WT) mice. Results: The results for male and female SOST KO mice were similar, with differences only in the magnitude of some effects. SOST KO mice had increased radiodensity throughout the skeleton, with general skeletal morphology being normal in appearance. DXA analysis of lumbar vertebrae and whole leg showed that there was a significant increase in BMD (>50%) at both sites. μCT analysis of femur showed that bone volume was significantly increased in both the trabecular and cortical compartments. Histomorphometry of trabecular bone revealed a significant increase in osteoblast surface and no significant change in osteoclast surface in SOST KO mice. The bone formation rate in SOST KO mice was significantly increased for trabecular bone (>9-fold) at the distal femur, as well as for the endocortical and periosteal surfaces of the femur midshaft. Mechanical testing of lumbar vertebrae and femur showed that bone strength was significantly increased at both sites in SOST KO mice. Conclusions: SOST KO mice have a high bone mass phenotype characterized by marked increases in BMD, bone volume, bone formation, and bone strength. These results show that sclerostin is a key negative regulator of a powerful, evolutionarily conserved bone formation pathway that acts on both trabecular and cortical bone.
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Cites
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High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
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Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling
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Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)
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“Mutations in a previously undescribed gene, SOST, were identified by positional cloning as being responsible for causing sclerosteosis.((3,4)) Sclerostin, the pro-”
BackgroundOsteocyte control of bone formation via sclerostin, a novel BMP antagonist
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Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation
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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
Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis
Saag, K. G., Petersen, J., Brandi, M. L., Karaplis, A. C., Lorentzon, M., Thomas, T., Maddox, J., Fan, M., Meisner, P. D., & Grauer, A. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1708322 · Cited by 1,544
Matrix-embedded cells control osteoclast formation
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Romosozumab in Postmenopausal Women with Low Bone Mineral Density
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Metadata
- Authors
- Li, X., Ominsky, M. S., Niu, Q.-T., Sun, N., Daugherty, B., D'Agostin, D., Kurahara, C., Gao, Y., Cao, J., Gong, J., Asuncion, F., Barrero, M., Warmington, K., Dwyer, D., Stolina, M., Morony, S., Sarosi, I., Kostenuik, P. J., Lacey, D. L., Simonet, W. S., Ke, H. Z., & Paszty, C.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06-01
- Volume
- 23
- Issue
- 6
- Pages
- 860-869
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2068916684
- Cited by
- 936
- References
- 28
- FWCI
- 52.12
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Li, X., Ominsky, M. S., Niu, Q.-T., Sun, N., Daugherty, B., D'Agostin, D., Kurahara, C., Gao, Y., Cao, J., Gong, J., Asuncion, F., Barrero, M., Warmington, K., Dwyer, D., Stolina, M., Morony, S., Sarosi, I., Kostenuik, P. J., Lacey, D. L., . . . Paszty, C. (2008). Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength. Journal of Bone and Mineral Research. https://doi.org/10.1359/jbmr.080216
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