Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
Osteoarthritis Cartilage. 2013 Jul;21(7):918-22. doi: 10.1016/j.joca.2013.04.002. Epub 2013 Apr 15.
Soluble mediators in synovial fluid (SF) are acknowledged as key players in the pathophysiology of osteoarthritis (OA). However, a wide-spectrum screening of such mediators in SF is currently lacking. In this study, the levels of 47 mediators in the SF of control donors and osteoarthritic (OA) patients were compared.
MATERIALS & METHODS: SF was collected from control donors (n = 16) and end-stage knee OA patients (n = 18) and analysed for 47 cytokines, chemokines and growth factors using several multiplex enzyme-linked immunosorbent assays (ELISAs). A Mann-Whitney U test was used to determine differences between OA and control controls. A principal component analysis (PCA) was performed to cluster the 47 mediators.
The majority of the mediators could be detected in both control and OA SF. Interleukin (IL)-6, interferon inducible protein (IP)-10, macrophage derived chemokine (MDC), platelet derived growth factor (PDGF)-AA and regulated on activation normal T cell expressed and secreted (RANTES) levels were found to be higher in OA compared to control SF (P < 0.001). Leptin, IL-13, macrophage inflammatory protein (MIP)-1β, soluble CD40 (sCD40L) levels were higher and eotaxin and granulocyte colony-stimulating factor (G-CSF) levels were lower in OA SF than in control SF, albeit borderline significant (P < 0.05). The PCA enabled identification of six clusters of mediators, which explained 76% of the variance.
The current study provides the first extensive profile of cytokines, chemokines and growth factors present in control and OA SF. Increased levels of mediators such as MDC and IL-6 imply involvement of inflammatory processes and might be associated with the influx of inflammatory cells in OA synovial tissue. Moreover, the performed cluster analysis indicated multiple clusters, which could indicate different pathophysiological pathways in the joint.
关节滑液（SF）中的可溶性介质被认为是骨关节炎（OA）病理生理学的关键因素。然而，目前缺乏对 SF 中此类介质的广谱筛选。在这项研究中，比较了对照组供体和骨关节炎（OA）患者 SF 中的 47 种介质的水平。
从对照组供体（n=16）和终末期膝 OA 患者（n=18）中采集 SF，并使用多种多重酶联免疫吸附测定（ELISA）分析 47 种细胞因子、趋化因子和生长因子。使用曼-惠特尼 U 检验确定 OA 与对照组之间的差异。进行主成分分析（PCA）以聚类 47 种介质。
大多数介质均可在对照和 OA SF 中检测到。白细胞介素（IL）-6、干扰素诱导蛋白（IP）-10、巨噬细胞来源的趋化因子（MDC）、血小板衍生生长因子（PDGF）-AA 和调节激活正常 T 细胞表达和分泌（RANTES）水平在 OA 中高于对照组 SF（P<0.001）。OA SF 中的瘦素、IL-13、巨噬细胞炎症蛋白（MIP）-1β、可溶性 CD40（sCD40L）水平较高，而 OA SF 中的嗜酸性粒细胞趋化因子和粒细胞集落刺激因子（G-CSF）水平较低，尽管有边缘意义（P<0.05）。PCA 可识别 6 个介质簇，可解释 76%的方差。
本研究首次提供了控制和 OA SF 中存在的细胞因子、趋化因子和生长因子的广泛概况。MDC 和 IL-6 等介质水平升高表明炎症过程的参与，并且可能与 OA 滑膜组织中炎症细胞的涌入有关。此外，进行的聚类分析表明存在多个聚类，这可能表明关节中的不同病理生理途径。
