Induction of an Inflammatory and Prodegradative Phenotype in Autologous Fibroblast-like Synoviocytes by the Infrapatellar Fat Pad From Patients With Knee Osteoarthritis
Induction of an Inflammatory and Prodegradative Phenotype in Autologous Fibroblast-like Synoviocytes by the Infrapatellar Fat Pad From Patients With Knee Osteoarthritis
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DOI：
10.1002/art.38657
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发表时间：
2014-08-01
影响因子：
13.3
通讯作者：
Houard, Xavier
中科院分区：
文献类型：
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作者：
Eymard, Florent;Pigenet, Audrey;Houard, Xavier
目标。膝关节的膝盖骨下脂肪垫(IFP)在骨关节炎(OA)中具有炎症性表型。IFP靠近滑膜，提示IFP可能参与了骨性关节炎滑膜炎的发生。本研究旨在探讨成纤维细胞样滑膜细胞(FLS)对自体IFP和严重膝关节OA患者皮下脂肪组织(SCAT)的反应。手术中采集了28例终末期膝关节骨性关节炎患者的IFP、SCAT和接近IFP的自体滑膜组织的样本。用自体IFP或SCAT条件培养液刺激14例患者的FLS，检测IL-6、IL-8、分泌型磷脂酶A(2)、胞浆磷脂酶A(2)、环氧合酶2(COX-2)、微体前列腺素E合成酶、前列腺素E-2(PGE(2))、基质金属蛋白酶(MMPs)1、3、9和13的信使RNA(MRNA)表达和蛋白释放水平。采用酶联免疫吸附试验检测IFP和SCAT条件培养液中IL-6、可溶性IL-6受体(sIL-6R)、IL-8、肿瘤坏死因子α(TNFα)、前列腺素E(2)、IL-1β和干扰素-γ的分泌。此外，用PGE(2)受体拮抗剂处理OAFLS，以评价IFP来源的PGE(2)在FLS对IFP的炎症反应中的作用。用IFP条件培养液刺激OA FLS后，IL-6、IL-8、SplA(2)、COX-2、PGE(2)和MMPs1、3、9、13的mRNA表达和蛋白释放均有增加，且IFP条件培养液的刺激作用明显强于SCAT条件培养液。IL-6、sIL-6R、IL-8、肿瘤坏死因子α和前列腺素E(2)的分泌量在IFP条件培养液中明显高于SCAT条件培养液，尤其是PGE(2)，其分泌量是IFP条件培养液的75倍(P<；0.0001)。PGE(2)受体拮抗剂呈剂量依赖性抑制IFP刺激的FL释放IL-6、IL-8和PGE(2)。这项研究表明，IFP在重度膝骨性关节炎患者的滑膜炎症诱导中具有潜在的作用。此外，IFP分泌的PGE(2)可能参与了骨性关节炎的炎症过程。
Objective. The infrapatellar fat pad (IFP) of the knee joint has an inflammatory phenotype in osteoarthritis (OA). Its close proximity to the synovial membrane suggests that the IFP could be involved in the induction of OA synovitis. This study was undertaken to investigate the response of fibroblast-like synoviocytes (FLS) to autologous IFP and subcutaneous adipose tissue (SCAT) from patients with severe knee OA.Methods. Samples of IFP, SCAT, and autologous synovial membrane tissue close to the IFP were harvested during surgery from 28 patients with end-stage knee OA. FLS from 14 patients were stimulated with autologous IFP- or SCAT-conditioned medium, and levels of messenger RNA (mRNA) expression and protein release of interleukin-6 (IL-6), IL-8, secretory phospholipase A(2) (sPLA(2)), cytosolic PLA(2), cyclooxygenase 2 (COX-2), microsomal prostaglandin E synthase, prostaglandin E-2 (PGE(2)), and matrix metalloproteinases (MMPs) 1, 3, 9, and 13 were evaluated. Both IFP- and SCAT-conditioned medium were evaluated by enzyme-linked immunosorbent assay for secretion of IL-6, soluble IL-6 receptor (sIL-6R), IL-8, tumor necrosis factor alpha (TNF alpha), PGE(2), IL-1 beta, and interferon-gamma. In addition, OA FLS were treated with PGE(2) receptor antagonists to evaluate the contribution of IFP-derived PGE(2) to the inflammatory response of FLS to the IFP.Results. Stimulation of OA FLS with IFP-conditioned medium induced the mRNA expression and protein release of IL-6, IL-8, sPLA(2), COX-2, PGE(2), and MMPs 1, 3, 9, and 13. The extent of stimulation was consistently stronger with IFP-conditioned medium than with SCAT-conditioned medium. Moreover, secretion of IL-6, sIL-6R, IL-8, TNF alpha, and PGE(2) was greater in IFP-conditioned medium than in SCAT-conditioned medium, especially PGE(2), whose secretion was 75-fold stronger in IFP-conditioned medium (P < 0.0001). PGE(2) receptor antagonists dose-dependently inhibited the release of IL-6, IL-8, and PGE(2) by IFP-stimulated FLS.Conclusion. This study showed that the IFP has a potential role in the induction of synovial inflammation in patients with severe knee OA. Furthermore, secretion of PGE(2) by the IFP may be involved in the OA inflammatory process.