The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals
Open accessAbstract
In diabetic LDLR-/- mice, an ectopic BMP2-Msx2 gene regulatory program is upregulated in association with vascular calcification. We verified the procalcific actions of aortic Msx2 expression in vivo. CMV-Msx2 transgenic (CMV-Msx2Tg(+)) mice expressed 3-fold higher levels of aortic Msx2 than nontransgenic littermates. On high-fat diets, CMV-Msx2Tg(+) mice exhibited marked cardiovascular calcification involving aortic and coronary tunica media. This corresponded to regions of Msx2 immunoreactivity in adjacent adventitial myofibroblasts, suggesting a potential paracrine osteogenic signal. To better understand Msx2-regulated calcification, we studied actions in 10T1/2 cells. We found that conditioned media from Msx2-transduced 10T1/2 cells (Msx2-CM) is both pro-osteogenic and adipostatic; these features are characteristic of Wnt signaling. Msx2-CM stimulated Wnt-dependent TCF/LEF transcription, and Msx2-transduced cells exhibited increased nuclear beta-catenin localization with concomitant alkaline phosphatase induction. Msx2 upregulated Wnt3a and Wnt7a but downregulated expression of the canonical inhibitor Dkk1. Dkk1 treatment reversed osteogenic and adipostatic actions of Msx2. Teriparatide, a PTH1R agonist that inhibits murine vascular calcification, suppressed vascular BMP2-Msx2-Wnt signaling. Analyses of CMV-Msx2Tg(+) mice confirmed that Msx2 suppresses aortic Dkk1 and upregulates vascular Wnts; moreover, TOPGAL(+) (Wnt reporter); CMV-Msx2Tg(+) mice exhibited augmented aortic LacZ expression. Thus, Msx2-expressing cells elaborated an osteogenic milieu that promotes vascular calcification in part via paracrine Wnt signals.
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Cites
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
Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling
Mao, B., Wu, W., Davidson, G., Marhold, J., Li, M., Mechler, B. M., Delius, H., Hoppe, D., Stannek, P., Walter, C., et al. (2002) · Nature · doi:10.1038/nature756 · Cited by 1,038
Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation
Satokata, I., Ma, L., Ohshima, H., Bei, M., Woo, I., Nishizawa, K., Maeda, T., Takano, Y., Uchiyama, M., Heaney, S., et al. (2000) · Nature Genetics · doi:10.1038/74231 · Cited by 737
Shao, J.-S., Cheng, S.-L., Charlton-Kachigian, N., Loewy, A. P., & Towler, D. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308825200 · Cited by 174
Self-citationReciprocal Roles of Msx2 in Regulation of Osteoblast and Adipocyte Differentiation
Ichida, F., Nishimura, R., Hata, K., Matsubara, T., Ikeda, F., Hisada, K., Yatani, H., Cao, X., Komori, T., Yamaguchi, A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403621200 · Cited by 173
Cited by
Lindman, B. R., Clavel, M.-A., Mathieu, P., Iung, B., Lancellotti, P., Otto, C. M., & Pibarot, P. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.6 · Cited by 982
Rajamannan, N. M., Evans, F. J., Aikawa, E., Grande-Allen, K. J., Demer, L. L., Heistad, D. D., Simmons, C. A., Masters, K. S., Mathieu, P., O'Brien, K. D., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.006767 · Cited by 842
Self-citationYahagi, K., Kolodgie, F. D., Lutter, C., Mori, H., Romero, M. E., Finn, A. V., & Virmani, R. (2017) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.116.306256 · Cited by 573
Vascular calcification: Mechanisms of vascular smooth muscle cell calcification
Leopold, J. A. (2015) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2014.10.021 · Cited by 468
Yutzey, K. E., Demer, L. L., Body, S. C., Huggins, G. S., Towler, D. A., Giachelli, C. M., Hofmann-Bowman, M. A., Mortlock, D. P., Rogers, M. B., Sadeghi, M. M., et al. (2014) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.114.302523 · Cited by 371
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Metadata
- Authors
- Shao, J.-S., Cheng, S.-L., Pingsterhaus, J. M., Charlton-Kachigian, N., Loewy, A. P., & Towler, D. A.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-04-14
- Volume
- 115
- Issue
- 5
- Pages
- 1210-1220
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2051580972
- Cited by
- 452
- References
- 5
- FWCI
- 11.76
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Shao, J.-S., Cheng, S.-L., Pingsterhaus, J. M., Charlton-Kachigian, N., Loewy, A. P., & Towler, D. A. (2005). Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals. Journal of Clinical Investigation. https://doi.org/10.1172/jci200524140
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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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