Transcriptomic profiling of osteoarthritis synovial macrophages reveals a tolerized phenotype compounded by a weak corticosteroid response.

Autor:	Wang C; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., De Francesco R; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands.; Experimental Rheumatology, Department of Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Lamers LA; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Rinzema S; Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., Frölich S; Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., van Lent PLEM; Experimental Rheumatology, Department of Rheumatology, Radboud university medical center, Nijmegen, the Netherlands., Logie C; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, the Netherlands., van den Bosch MHJ; Experimental Rheumatology, Department of Rheumatology, Radboud university medical center, Nijmegen, the Netherlands.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2024 Mar 11. Date of Electronic Publication: 2024 Mar 11.
DOI:	10.1093/rheumatology/keae161
Abstrakt:	Objectives: It is well-known that long-term osteoarthritis prognosis is not improved by corticosteroid treatments. Here we investigate what could underlie this phenomenon by measuring the short term corticosteroid response of OA-Mf. Methods: We determined the genome-wide transcriptomic response to corticosteroids of end-stage osteoarthritic joint synovial macrophages (OA-Mf). This was compared with LPS-tolerized and β-glucan-trained circulating blood monocyte-derived macrophage models. Results: Upon corticosteroid stimulation, the trained and tolerized macrophages significantly alter the abundance of 201 and 257 RNA transcripts, respectively. By contrast, by the same criteria, OA-Mf have a very restricted corticosteroid response of only 12 RNA transcripts. Furthermore, while metalloproteinases 1, -2, -3 and -10 expression clearly distinguish OA-Mf from both the tolerized and trained macrophage models, OA-Mf Interleukin 1 (IL1), chemokine (CXCL) and cytokine (CCL) family member profiles resemble the tolerized macrophage model, with the exception that OA-Mf show high levels of CCL20. Conclusion: Terminal osteoarthritis joints therefore harbor macrophages with an inflammatory state that closely resembles the tolerized macrophage state and this is compounded by a weak corticosteroid response capacity that may explain the lack of positive long-term effects of corticosteroid treatment for osteoarthritis patients. (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu