The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Wnt signalling in osteoblasts regulates expression of the receptor activator of NFκB ligand and inhibits osteoclastogenesis in vitro
Abstract
Reports implicating Wnt signalling in the regulation of bone mass have prompted widespread interest in the use of Wnt mimetics for the treatment of skeletal disorders. To date much of this work has focused on their anabolic effects acting on cells of the osteoblast lineage. In this study we provide evidence that Wnts also regulate osteoclast formation and bone resorption, through a mechanism involving transcriptional repression of the gene encoding the osteoclastogenic cytokine receptor activator of NFκB ligand (RANKL or TNFSF11) expressed by osteoblasts. In co-cultures of mouse mononuclear spleen cells and osteoblasts, inhibition of GSK3β with LiCl or exposure to Wnt3a inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated cells compared with controls. However, these treatments had no consistent effect on the differentiation, survival or activity of osteoclasts generated in the absence of supporting stromal cells. Activation of Wnt signalling downregulated RANKL mRNA and protein expression, and overexpression of fulllength β-catenin, but not transcriptionally inactive β-catenin ΔC(695-781), inhibited RANKL promoter activity. Since previous studies have demonstrated an absence of resorptive phenotype in mice lacking LRP5, we determined expression of a second Wnt co-receptor LRP6 in human osteoblasts, CD14+ osteoclast progenitors and mature osteoclasts. LRP5 expression was undetectable in CD14-enriched cells and mature human osteoclasts, although LRP6 was expressed at high levels by these cells. Our evidence of Wnt-dependent regulation of osteoclastogenesis adds to the growing complexity of Wnt signalling mechanisms that are now known to influence skeletal function and highlights the requirement to develop novel therapeutics that differentially target anabolic and catabolic Wnt effects in bone.
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Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T., & Martin, T. J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0367 · Cited by 2,336
A molecular mechanism for the effect of lithium on development.
Klein, P. S., & Melton, D. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8455 · Cited by 2,301
Wnt proteins are lipid-modified and can act as stem cell growth factors
Willert, K., Brown, J. D., Danenberg, E., Duncan, A. W., Weissman, I. L., Reya, T., Yates, J. R., & Nusse, R. (2003) · Nature · doi:10.1038/nature01611 · Cited by 2,257
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00571-2 · Cited by 2,235
Therapeutic Approaches to Bone Diseases
Rodan, G. A., & Martin, T. J. (2000) · Science · doi:10.1126/science.289.5484.1508 · Cited by 1,767
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5
Boyden, L. M., Mao, J., Belsky, J., Mitzner, L., Farhi, A., Mitnick, M. A., Wu, D., Insogna, K., & Lifton, R. P. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa013444 · Cited by 1,591
Canonical wnt signaling in differentiated osteoblasts controls osteoclast differentiation.
Glass, D. A., Bialek, P., Ahn, J. D., Starbuck, M., Patel, M. S., Clevers, H., Taketo, M. M., Long, F., McMahon, A. P., Lang, R. A., et al. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.02.017 · Cited by 1,558
Tian, E., Zhan, F., Walker, R., Rasmussen, E., Ma, Y., Barlogie, B., & Shaughnessy, J. D. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030847 · Cited by 1,503
Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells
Stambolic, V., Ruel, L., & Woodgett, J. R. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70790-2 · Cited by 1,321
Little, R. D., Folz, C., Manning, S. P., Swain, P. M., Zhao, S.-C., Eustace, B., Lappe, M. M., Spitzer, L., Zweier, S., Braunschweiger, K., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/338450 · Cited by 1,282
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The role of Dickkopf-1 in bone development, homeostasis, and disease
Pinzone, J. J., Hall, B. M., Thudi, N. K., Vonau, M., Qiang, Y.-W., Rosol, T. J., & Shaughnessy, J. D. (2009) · Blood · doi:10.1182/blood-2008-03-145169 · Cited by 408
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Roodman, G. D. (2009) · Leukemia · doi:10.1038/leu.2008.336 · Cited by 398
Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease
Hu, L., Chen, W., Qian, A., & Li, Y.-P. (2024) · Bone Research · doi:10.1038/s41413-024-00342-8 · Cited by 359
Delmas, V., Beermann, F., Martinozzi, S., Carreira, S., Ackermann, J., Kumasaka, M., Denat, L., Goodall, J., Luciani, F., Viros, A., et al. (2007) · Genes & Development · doi:10.1101/gad.450107 · Cited by 311
Metadata
- Authors
- Spencer, G. J., Utting, J. C., Etheridge, S. L., Arnett, T. R., & Genever, P. G.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2006-04-01
- Volume
- 119
- Issue
- 7
- Pages
- 1283-1296
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2149248348
- Cited by
- 334
- References
- 60
- FWCI
- 8.23
- Type
- journal article
- Language
- en
- Open access
- closed
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- Spencer, G. J., Utting, J. C., Etheridge, S. L., Arnett, T. R., & Genever, P. G. (2006). Wnt signalling in osteoblasts regulates expression of the receptor activator of NFκB ligand and inhibits osteoclastogenesis in vitro. Journal of Cell Science. https://doi.org/10.1242/jcs.02883
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