The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β-Catenin Signaling
Open accessAbstract
Reduced mechanical stress leads to bone loss, as evidenced by disuse osteoporosis in bedridden patients and astronauts. Osteocytes have been identified as major cells responsible for mechanotransduction; however, the mechanism underlying the response of bone to mechanical unloading remains poorly understood. In this study, we found that mechanical unloading of wildtype mice caused decrease of Wnt/β-catenin signaling activity accompanied by upregulation of Sost. To further analyze the causal relationship among these events, Sost gene targeting mice were generated. We showed that sclerostin selectively inhibited Wnt/β-catenin in vivo, and sclerostin suppressed the activity of osteoblast and viability of osteoblasts and osteocytes. Interestingly, Sost−/− mice were resistant to mechanical unloading-induced bone loss. Reduction in bone formation in response to unloading was also abrogated in the mutant mice. Moreover, in contrast to wildtype mice, Wnt/β-catenin signaling was not altered by unloading in Sost−/− mice. Those data implied that sclerostin played an essential role in mediating bone response to mechanical unloading, likely through Wnt/β-catenin signaling. Our findings also indicated sclerostin is a promising target for preventing disuse osteoporosis.
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Citations
Cites
Regulation of bone mass by Wnt signaling
Krishnan, V. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28551 · Cited by 1,407
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 · cited 3×
“gether with previous data that sclerostin bound to Lrp5/Lrp6 and inhibited Wnt/b-catenin signaling in vitro,((19,20)) strongly implied sclerostin was an antagonist of Wnt/b-catenin sig-”
BackgroundResultMechanical Stimulation of Bone in Vivo Reduces Osteocyte Expression of Sost/Sclerostin
Robling, A. G., Niziolek, P. J., Baldridge, L. A., Condon, K. W., Allen, M. R., Alam, I., Mantila, S. M., Gluhak-Heinrich, J., Bellido, T. M., Harris, S. E., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705092200 · Cited by 1,350
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
Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation
Poole, K. E. S., Van Bezooijen, R. L., Loveridge, N., Hamersma, H., Papapoulos, S. E., Löwik, C. W., & Reeve, J. (2005) · The FASEB Journal · doi:10.1096/fj.05-4221fje · Cited by 965
Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow
Bafico, A., Liu, G., Yaniv, A., Gazit, A., & Aaronson, S. A. (2001) · Nature Cell Biology · doi:10.1038/35083081 · Cited by 772
Identification 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
The Osteocyte: An Endocrine Cell … and More
Dallas, S. L., Prideaux, M., & Bonewald, L. F. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1026 · Cited by 1,042
Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms
Booth, F. W., Roberts, C. K., Thyfault, J. P., Ruegsegger, G. N., & Toedebusch, R. G. (2017) · Physiological Reviews · doi:10.1152/physrev.00019.2016 · Cited by 696
Osteocyte Wnt/β-Catenin Signaling Is Required for Normal Bone Homeostasis
Kramer, I., Halleux, C., Keller, H., Pegurri, M., Gooi, J. H., Weber, P. B., Feng, J. Q., Bonewald, L. F., & Kneissel, M. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01428-09 · Cited by 567
Metadata
- Authors
- Lin, C., Jiang, X., Dai, Z., Guo, X., Weng, T., Wang, J., Li, Y., Feng, G., Gao, X., & He, L.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-10-01
- Volume
- 24
- Issue
- 10
- Pages
- 1651-1661
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2043991983
- Cited by
- 628
- References
- 8
- FWCI
- 42.57
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lin, C., Jiang, X., Dai, Z., Guo, X., Weng, T., Wang, J., Li, Y., Feng, G., Gao, X., & He, L. (2009). Sclerostin Mediates Bone Response to Mechanical Unloading Through Antagonizing Wnt/β-Catenin Signaling. Journal of Bone and Mineral Research. https://doi.org/10.1359/jbmr.090411
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