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
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.
Rheumatology (Oxford). 2025 Feb 1;64(2):860-869. doi: 10.1093/rheumatology/keae161.
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).
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.
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.
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.
众所周知，皮质类固醇治疗并不能改善骨关节炎的长期预后。在此，我们通过测量骨关节炎关节滑膜巨噬细胞（OA-Mf）的短期皮质类固醇反应，来探究这一现象的潜在原因。
我们测定了终末期OA-Mf对皮质类固醇的全基因组转录反应。并将其与脂多糖耐受和β-葡聚糖训练的循环血单核细胞衍生巨噬细胞模型进行比较。
在皮质类固醇刺激下，经过训练和耐受的巨噬细胞分别显著改变了201个和257个RNA转录本的丰度。相比之下，按照相同标准，OA-Mf对皮质类固醇的反应非常有限，只有12个RNA转录本。此外，虽然金属蛋白酶1、2、3和10的表达明显区分了OA-Mf与耐受和训练的巨噬细胞模型，但OA-Mf的白细胞介素-1、趋化因子（CXCL）和细胞因子（CCL）家族成员谱与耐受巨噬细胞模型相似，不同之处在于OA-Mf显示出高水平的CCL20。
终末期骨关节炎关节中的巨噬细胞具有与耐受巨噬细胞状态非常相似的炎症状态，并且这种情况因皮质类固醇反应能力较弱而更加严重，这可能解释了皮质类固醇治疗对骨关节炎患者缺乏长期积极效果的原因。
