Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.
Synergistic Roles of Macrophages and Neutrophils in Osteoarthritis Progression.
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DOI：
10.1002/art.41486
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Kraus VB
中科院分区：
文献类型：
--
作者：
Hsueh MF;Zhang X;Wellman SS;Bolognesi MP;Kraus VB
目的探讨关节滑液（SF）和滑膜（SV）中免疫细胞及其效应细胞因子在骨关节炎（OA）发病和进展中的作用。SV和匹配的SF细胞获得的个人接受全膝关节置换术的OA（n=39）的特点是免疫细胞相关的表面标志物和细胞内细胞因子的表达，使用多色流式细胞术。其他放射学膝关节OA（Kellgren Lawrence分级≥1）患者有可用的骨显像（炎性细胞显像，n=26）或基线和3年膝关节放射学OA进展（n=85）数据。评价所有队列的SF细胞因子浓度与SV和SF细胞表型和放射学OA严重程度的相关性。巨噬细胞（SV为主，占总细胞的53%）和中性粒细胞（SF为主，占总细胞的26%）是OA关节中的主要免疫细胞群，分别表达SF转化生长因子β-1（TGF-β1）和弹性蛋白酶并与其相关。TGF-β1和弹性蛋白酶与放射学膝关节OA严重程度显著相关。基线SF浓度和影像学评分预测膝关节OA进展，受试者工作特征曲线下面积分别为0.810（TGF-β1）、0.806（弹性蛋白酶）和0.846（组合），当两者均使用时，预测的稳定性更高。我们的研究结果表明，中性粒细胞在OA的无菌炎症过程和进展中的作用迄今未被充分认识。可溶性介质SF弹性蛋白酶和TGF-β1是OA进展的强预测因子，反映了中性粒细胞和巨噬细胞群体在OA发病机制和恶化中的协同作用，可能用于识别具有更快疾病进展风险的患者。
To evaluate the role of immune cells and their effector cytokines from matched synovial fluid (SF) and synovium (SV) in the pathogenesis and progression of osteoarthritis (OA). SV and matched SF cells acquired from individuals undergoing total knee replacement for OA (n=39) were characterized for immune cell-associated surface markers and intracellular cytokine expression using polychromatic flow cytometry. Additional individuals with radiographic knee OA (Kellgren Lawrence grades ≥1) had available etarfolatide imaging (inflammatory cell imaging, n=26) or baseline and 3-year knee radiographic OA progression (n=85) data. SF cytokine concentrations of all cohorts were evaluated for associations with SV and SF cell phenotypes and radiographic OA severity. Macrophages (SV predominant, 53% of total cells) and neutrophils (SF predominant, 26% of total cells) were the major immune cell populations in OA joints, expressing and associated with SF transforming growth factor beta-1 (TGF-β1) and elastase, respectively. TGF-β1 and elastase were significantly associated with radiographic knee OA severity. Baseline SF concentrations with radiographic scores predicted knee OA progression with areas under the Receiver Operating Characteristic curves of 0.810 (TGF-β1), 0.806 (elastase), and 0.846 (combination), with greater stability of prediction when both were utilized. Our findings demonstrate the hitherto under-appreciated role of neutrophils in the sterile inflammatory process and progression of OA. The soluble mediators, SF elastase and TGF-β1, are strong predictors of OA progression reflecting a synergistic role of neutrophil and macrophage populations in the pathogenesis and worsening of OA that could potentially be utilized to identify patients with risk for more rapid disease progression.
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滑膜巨噬细胞和巨噬细胞产生的细胞因子在驱动聚集蛋白聚糖酶、基质金属蛋白酶和骨关节炎中其他破坏性和炎症反应中的作用。
影响因子：
4.9
作者：
Bondeson J;Wainwright SD;Lauder S;Amos N;Hughes CE
通讯作者：
Hughes CE
影响因子：
27.4
作者：
Atukorala I;Kwoh CK;Guermazi A;Roemer FW;Boudreau RM;Hannon MJ;Hunter DJ
通讯作者：
Hunter DJ
影响因子：
27.4
作者：
Huesa C;Ortiz AC;Dunning L;McGavin L;Bennett L;McIntosh K;Crilly A;Kurowska-Stolarska M;Plevin R;van 't Hof RJ;Rowan AD;McInnes IB;Goodyear CS;Lockhart JC;Ferrell WR
通讯作者：
Ferrell WR
影响因子：
4.6
作者：
Cheon, H;Yu, SJ;Sohn, J
通讯作者：
Sohn, J
影响因子：
27.4
作者：
Bruyere, O;Richy, F;Reginster, JY
通讯作者：
Reginster, JY