Objective Rheumatoid arthritis (RA) accompanies infiltration and activation of monocytes in inflamed joints. We investigated dominant alterations of RA monocytes in bone marrow (BM), blood and inflamed joints. Methods CD14+ cells from BM and peripheral blood (PB) of patients with RA and osteoarthritis (OA) were profiled with GeneChip microarrays. Detailed functional analysis was performed with reference transcriptomes of BM precursors, monocyte blood subsets, monocyte activation and mobilisation. Cytometric profiling determined monocyte subsets of CD14++CD16−, CD14++CD16+ and CD14+CD16+ cells in BM, PB and synovial fluid (SF) and ELISAs quantified the release of activation markers into SF and serum. Results Investigation of genes differentially expressed between RA and OA monocytes with reference transcriptomes revealed gene patterns of early myeloid precursors in RA-BM and late myeloid precursors along with reduced terminal differentiation to CD14+CD16+monocytes in RA-PB. Patterns associated with tumor necrosis factor/lipopolysaccharide (TNF/LPS) stimulation were weak and more pronounced in RA-PB than RA-BM. Cytometric phenotyping of cells in BM, blood and SF disclosed differences related to monocyte subsets and confirmed the reduced frequency of terminally differentiated CD14+CD16+monocytes in RA-PB. Monocyte activation in SF was characterised by the predominance of CD14++CD16++CD163+HLA-DR+ cells and elevated concentrations of sCD14, sCD163 and S100P. Conclusion Patterns of less mature and less differentiated RA-BM and RA-PB monocytes suggest increased turnover with accelerated monocytopoiesis, BM egress and migration into inflamed joints. Predominant activation in the joint indicates the action of local and primary stimuli, which may also promote adaptive immune triggering through monocytes, potentially leading to new diagnostic and therapeutic strategies.

中文翻译：

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类风湿性关节炎的单核细胞改变主要是从骨髓中早产释放和关节中的显着触发

目的类风湿性关节炎 (RA) 伴随发炎关节中单核细胞的浸润和活化。我们研究了骨髓 (BM)、血液和发炎关节中 RA 单核细胞的显性改变。方法 使用 GeneChip 微阵列分析 RA 和骨关节炎 (OA) 患者 BM 和外周血 (PB) 的 CD14+ 细胞。使用 BM 前体、单核细胞血亚群、单核细胞活化和动员的参考转录组进行了详细的功能分析。细胞分析确定了 BM、PB 和滑液 (SF) 中 CD14++CD16-、CD14++CD16+ 和 CD14+CD16+ 细胞的单核细胞亚群，ELISA 量化了激活标记物释放到 SF 和血清中。结果 使用参考转录组对 RA 和 OA 单核细胞之间差异表达的基因的研究揭示了 RA-BM 中早期髓样前体和晚期髓样前体的基因模式，以及 RA-PB 中向 CD14+CD16+单核细胞的终末分化减少。与肿瘤坏死因子/脂多糖 (TNF/LPS) 刺激相关的模式在 RA-PB 中比在 RA-BM 中弱且更明显。BM、血液和 SF 中细胞的细胞学表型分析揭示了与单核细胞亚群相关的差异，并证实了 RA-PB 中终末分化的 CD14+CD16+单核细胞的频率降低。SF 中单核细胞活化的特点是 CD14++CD16++CD163+HLA-DR+ 细胞占优势，sCD14、sCD163 和 S100P 浓度升高。结论 不太成熟和分化程度较低的 RA-BM 和 RA-PB 单核细胞的模式表明，随着单核细胞生成、BM 流出和迁移到发炎关节的加速，周转增加。关节中的主要激活表明局部和初级刺激的作用，这也可能通过单核细胞促进适应性免疫触发，可能导致新的诊断和治疗策略。