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Wang, Cheng; De Francesco, Ruben; Lamers, Lieke A; Rinzema, Sybren; Frölich, Siebren; van Lent, Peter L E M; Logie, Colin; van den Bosch, Martijn H J

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

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  • Medientyp: E-Artikel
  • Titel: Transcriptomic profiling of osteoarthritis synovial macrophages reveals a tolerized phenotype compounded by a weak corticosteroid response
  • Beteiligte: Wang, Cheng; De Francesco, Ruben; Lamers, Lieke A; Rinzema, Sybren; Frölich, Siebren; van Lent, Peter L E M; Logie, Colin; van den Bosch, Martijn H J
  • Erschienen: Oxford University Press (OUP), 2024
  • Erschienen in: Rheumatology
  • Sprache: Englisch
  • DOI: 10.1093/rheumatology/keae161
  • ISSN: 1462-0324; 1462-0332
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objectives</jats:title> <jats:p>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 osteoarthritic joint synovial macrophages (OA-Mf).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We determined the genome-wide transcriptomic response to corticosteroids of end-stage OA-Mf. This was compared with lipopolysaccharide-tolerized and β-glucan-trained circulating blood monocyte-derived macrophage models.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Upon corticosteroid stimulation, the trained and tolerized macrophages significantly altered the abundance of 201 and 257 RNA transcripts, respectively. By contrast, by the same criteria, OA-Mf had 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 IL-1, chemokine (CXCL) and cytokine (CCL) family member profiles resembled the tolerized macrophage model, with the exception that OA-Mf showed high levels of CCL20.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Terminal osteoarthritis joints harbour 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.</jats:p> </jats:sec>