IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

Abstract The IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains el...

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Autores principales:	Wida Razawy, Celso H. Alves, Marijke Koedam, Patrick S. Asmawidjaja, Adriana M. C. Mus, Mohamed Oukka, Pieter J. M. Leenen, Jenny A. Visser, Bram C. J. van der Eerden, Erik Lubberts
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4178bd5619304f8498fcb69ed29bb6bc
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spelling	oai:doaj.org-article:4178bd5619304f8498fcb69ed29bb6bc2021-12-02T15:43:08ZIL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation10.1038/s41598-021-89625-22045-2322https://doaj.org/article/4178bd5619304f8498fcb69ed29bb6bc2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89625-2https://doaj.org/toc/2045-2322Abstract The IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains elusive. Therefore, we studied the role of IL-23R signaling in physiological bone remodeling using IL-23R deficient mice. Using µCT, we demonstrate that 7-week-old IL-23R−/− mice have similar bone mass as age matched littermate control mice. In contrast, 12-week-old IL-23R−/− mice have significantly lower trabecular and cortical bone mass, shorter femurs and more fragile bones. At the age of 26 weeks, there were no differences in trabecular bone mass and femur length, but most of cortical bone mass parameters remain significantly lower in IL-23R−/− mice. In vitro osteoclast differentiation and resorption capacity of 7- and 12-week-old IL-23R−/− mice are similar to WT. However, serum levels of the bone formation marker, PINP, are significantly lower in 12-week-old IL-23R−/− mice, but similar to WT at 7 and 26 weeks. Interestingly, Il23r gene expression was not detected in in vitro cultured osteoblasts, suggesting an indirect effect of IL-23R. In conclusion, IL-23R deficiency results in temporal and long-term changes in bone growth via regulation of bone formation.Wida RazawyCelso H. AlvesMarijke KoedamPatrick S. AsmawidjajaAdriana M. C. MusMohamed OukkaPieter J. M. LeenenJenny A. VisserBram C. J. van der EerdenErik LubbertsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wida Razawy Celso H. Alves Marijke Koedam Patrick S. Asmawidjaja Adriana M. C. Mus Mohamed Oukka Pieter J. M. Leenen Jenny A. Visser Bram C. J. van der Eerden Erik Lubberts IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
description	Abstract The IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains elusive. Therefore, we studied the role of IL-23R signaling in physiological bone remodeling using IL-23R deficient mice. Using µCT, we demonstrate that 7-week-old IL-23R−/− mice have similar bone mass as age matched littermate control mice. In contrast, 12-week-old IL-23R−/− mice have significantly lower trabecular and cortical bone mass, shorter femurs and more fragile bones. At the age of 26 weeks, there were no differences in trabecular bone mass and femur length, but most of cortical bone mass parameters remain significantly lower in IL-23R−/− mice. In vitro osteoclast differentiation and resorption capacity of 7- and 12-week-old IL-23R−/− mice are similar to WT. However, serum levels of the bone formation marker, PINP, are significantly lower in 12-week-old IL-23R−/− mice, but similar to WT at 7 and 26 weeks. Interestingly, Il23r gene expression was not detected in in vitro cultured osteoblasts, suggesting an indirect effect of IL-23R. In conclusion, IL-23R deficiency results in temporal and long-term changes in bone growth via regulation of bone formation.
format	article
author	Wida Razawy Celso H. Alves Marijke Koedam Patrick S. Asmawidjaja Adriana M. C. Mus Mohamed Oukka Pieter J. M. Leenen Jenny A. Visser Bram C. J. van der Eerden Erik Lubberts
author_facet	Wida Razawy Celso H. Alves Marijke Koedam Patrick S. Asmawidjaja Adriana M. C. Mus Mohamed Oukka Pieter J. M. Leenen Jenny A. Visser Bram C. J. van der Eerden Erik Lubberts
author_sort	Wida Razawy
title	IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
title_short	IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
title_full	IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
title_fullStr	IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
title_full_unstemmed	IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
title_sort	il-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4178bd5619304f8498fcb69ed29bb6bc
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IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

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