IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity.
IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity.
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DOI：
10.1038/s41598-017-03759-w
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发表时间：
2017-06-14
影响因子：
4.6
通讯作者：
Lord JM
中科院分区：
文献类型：
--
作者：
Pearson MJ;Herndler-Brandstetter D;Tariq MA;Nicholson TA;Philp AM;Smith HL;Davis ET;Jones SW;Lord JM
越来越多的证据表明，炎症在某些骨性关节炎(OA)患者的关节病理中起着核心作用。由于许多髋关节骨性关节炎患者肥胖且肥胖增加与慢性炎症相关，我们调查了髋部骨性关节炎肥胖患者与正常体重的髋部骨性关节炎患者相比，是否表现出不同的促炎细胞因子信号以及外周和局部淋巴细胞群。在肥胖和正常体重的髋关节骨性关节炎患者之间，没有发现外周血或局部淋巴细胞群的差异。然而，与体重正常的患者相比，肥胖的骨性关节炎患者的滑膜成纤维细胞分泌了更多的促炎细胞因子IL-6(p <； 0.05)，这反映了在肥胖的骨性关节炎患者的滑液中检测到的更高的IL-6水平。对炎症机制的研究表明，滑膜成纤维细胞分泌IL-6是由软骨细胞来源的IL-6诱导的。此外，这种由软骨细胞-滑膜成纤维细胞相互作用介导的IL-6炎症反应，被肥胖相关的脂肪因子瘦素增强。这项研究表明，肥胖通过增加促炎脂肪因子瘦素的水平，增强了软骨细胞和滑膜成纤维细胞之间的相互作用，导致OA患者产生更多的IL-6。
Increasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p < 0.05), which reflected the greater levels of IL-6 detected in the synovial fluid of the obese OA patients. Investigation into the inflammatory mechanism demonstrated that IL-6 secretion from synovial fibroblasts was induced by chondrocyte-derived IL-6. Furthermore, this IL-6 inflammatory response, mediated by chondrocyte-synovial fibroblast cross-talk, was enhanced by the obesity-related adipokine leptin. This study suggests that obesity enhances the cross-talk between chondrocytes and synovial fibroblasts via raised levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA patients.