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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 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.

SUBMITTER: Razawy W

PROVIDER: S-EPMC8119722 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Razawy Wida W Alves Celso H CH Koedam Marijke M Asmawidjaja Patrick S PS Mus Adriana M C AMC Oukka Mohamed M Leenen Pieter J M PJM Visser Jenny A JA van der Eerden Bram C J BCJ Lubberts Erik E

Scientific reports 20210513 1

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<sup>-/-</sup> mice have similar bone mas ...[more]

PMID: 33986359

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

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

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