The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists
Open accessAbstract
Heterotopic ossification consists of ectopic bone formation within soft tissues after surgery or trauma. It can have debilitating consequences, but there is no definitive cure. Here we show that heterotopic ossification was essentially prevented in mice receiving a nuclear retinoic acid receptor-γ (RAR-γ) agonist. Side effects were minimal, and there was no significant rebound effect. To uncover the mechanisms of these responses, we treated mouse mesenchymal stem cells with an RAR-γ agonist and transplanted them into nude mice. Whereas control cells formed ectopic bone masses, cells that had been pretreated with the RAR-γ agonist did not, suggesting that they had lost their skeletogenic potential. The cells became unresponsive to rBMP-2 treatment in vitro and showed decreases in phosphorylation of Smad1, Smad5 and Smad8 and in overall levels of Smad proteins. In addition, an RAR-γ agonist blocked heterotopic ossification in transgenic mice expressing activin receptor-like kinase-2 (ALK2) Q207D, a constitutively active form of the receptor that is related to ALK2 R206H found in individuals with fibrodysplasia ossificans progressiva. The data indicate that RAR-γ agonists are potent inhibitors of heterotopic ossification in mouse models and, thus, may also be effective against injury-induced and congenital heterotopic ossification in humans.
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Cites
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The retinoids—Biology, chemistry and medicine
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BMP type I receptor inhibition reduces heterotopic ossification
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Self-citationHeterotopic ossification: A review
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Miron, R. J., & Zhang, Y. F. (2012) · Journal of Dental Research · doi:10.1177/0022034511435260 · Cited by 334
Tissue Engineering and Regenerative Medicine: Recent Innovations and the Transition to Translation
Fisher, M. B., & Mauck, R. L. (2013) · Tissue Engineering Part B: Reviews · doi:10.1089/ten.teb.2012.0723 · Cited by 263
Emerging roles for retinoids in regeneration and differentiation in normal and disease states
Gudas, L. J. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.08.002 · Cited by 158
Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling
Rauner, M., Baschant, U., Roetto, A., Pellegrino, R. M., Rother, S., Salbach-Hirsch, J., Weidner, H., Hintze, V., Campbell, G., Petzold, A., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-018-0005-8 · Cited by 87
Metadata
- Authors
- Shimono, K., Tung, W.-E., Macolino, C., Chi, A. H.-T., Didizian, J. H., Mundy, C., Chandraratna, R. A., Mishina, Y., Enomoto-Iwamoto, M., Pacifici, M., & Iwamoto, M.
- Venue
- Nature Medicine
- Published
- 2011-04
- Volume
- 17
- Issue
- 4
- Pages
- 454-460
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2088295232
- Cited by
- 334
- References
- 35
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- green
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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).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
