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IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappa B (RANK) expression in myeloid precursor cells

Chen, Li, Wei, Xiao-Qing ORCID: https://orcid.org/0000-0002-6274-8503, Evans, Bronwen Alice James ORCID: https://orcid.org/0000-0002-3082-1008, Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111 and Aeschlimann, Daniel ORCID: https://orcid.org/0000-0003-0930-7706 2008. IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappa B (RANK) expression in myeloid precursor cells. European Journal of Immunology 38 (10) , pp. 2845-2854. 10.1002/eji.200838192

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Abstract

Inflammation-mediated bone loss is a major feature of various bone diseases including rheumatoid arthritis, osteoarthritis and advanced periodontitis. Enhanced osteoclast development or activity at the inflammation site results in bone resorption. IL-23 is a heterodimeric cytokine belonging to the IL-6/IL-12 family that has been implicated in the pathogenesis of rheumatoid arthritis and demonstrated to play a role in osteoclastogenesis via stimulation of IL-17 production. in this study we investigated whether IL-23 contributes to the regulation of osteoclast differentiation independent of the IL-17 pathway. We show that IL-23 dose-dependently up-regulates receptor activator of NF-kappa B expression in primary murine bone marrow macrophages and RAW264.7 cells and thereby promotes commitment of myeloid precursor cells to receptor activator of NF-kappa B ligand-mediated osteoclastic differentiation. However, IL-23 by itself is insufficient to induce osteoclastogenesis. increased osteoclastic differentiation of cells was associated with enhanced cathepsin K expression and dentine resorption indicating enhanced formation of functional osteoclasts. IL-17 was not detectable in culture supernatants and when added to cultures, did not promote differentiation of RAW264.7 cells. These results demonstrate that IL-23 can act directly on myeloid precursor cells in addition to indirectly stimulating receptor activator of NF-kappa B ligand production in osteoblasts and explains its potency in driving osteoclast development in inflammation-mediated bone pathology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: John Wiley & Sons
ISSN: 0014-2980
Last Modified: 18 Oct 2022 13:53
URI: https://orca.cardiff.ac.uk/id/eprint/15804

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