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Interleukin 17A: a Janus-faced regulator of osteoporosis

Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in ost...

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Autores principales: Scheffler, J. M., Grahnemo, L., Engdahl, C., Drevinge, C., Gustafsson, K. L., Corciulo, C., Lawenius, L., Iwakura, Y., Sjögren, K., Lagerquist, M. K., Carlsten, H., Ohlsson, C., Islander, U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105470/
https://www.ncbi.nlm.nih.gov/pubmed/32231224
http://dx.doi.org/10.1038/s41598-020-62562-2
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author Scheffler, J. M.
Grahnemo, L.
Engdahl, C.
Drevinge, C.
Gustafsson, K. L.
Corciulo, C.
Lawenius, L.
Iwakura, Y.
Sjögren, K.
Lagerquist, M. K.
Carlsten, H.
Ohlsson, C.
Islander, U.
author_facet Scheffler, J. M.
Grahnemo, L.
Engdahl, C.
Drevinge, C.
Gustafsson, K. L.
Corciulo, C.
Lawenius, L.
Iwakura, Y.
Sjögren, K.
Lagerquist, M. K.
Carlsten, H.
Ohlsson, C.
Islander, U.
author_sort Scheffler, J. M.
collection PubMed
description Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which is of importance for the development of new treatments of post-menopausal osteoporosis.
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spelling pubmed-71054702020-04-06 Interleukin 17A: a Janus-faced regulator of osteoporosis Scheffler, J. M. Grahnemo, L. Engdahl, C. Drevinge, C. Gustafsson, K. L. Corciulo, C. Lawenius, L. Iwakura, Y. Sjögren, K. Lagerquist, M. K. Carlsten, H. Ohlsson, C. Islander, U. Sci Rep Article Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which is of importance for the development of new treatments of post-menopausal osteoporosis. Nature Publishing Group UK 2020-03-30 /pmc/articles/PMC7105470/ /pubmed/32231224 http://dx.doi.org/10.1038/s41598-020-62562-2 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Scheffler, J. M.
Grahnemo, L.
Engdahl, C.
Drevinge, C.
Gustafsson, K. L.
Corciulo, C.
Lawenius, L.
Iwakura, Y.
Sjögren, K.
Lagerquist, M. K.
Carlsten, H.
Ohlsson, C.
Islander, U.
Interleukin 17A: a Janus-faced regulator of osteoporosis
title Interleukin 17A: a Janus-faced regulator of osteoporosis
title_full Interleukin 17A: a Janus-faced regulator of osteoporosis
title_fullStr Interleukin 17A: a Janus-faced regulator of osteoporosis
title_full_unstemmed Interleukin 17A: a Janus-faced regulator of osteoporosis
title_short Interleukin 17A: a Janus-faced regulator of osteoporosis
title_sort interleukin 17a: a janus-faced regulator of osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105470/
https://www.ncbi.nlm.nih.gov/pubmed/32231224
http://dx.doi.org/10.1038/s41598-020-62562-2
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