The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis
The role of resolvin D1 in the regulation of inflammatory and catabolic mediators in osteoarthritis
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DOI：
10.1007/s00011-016-0946-x
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发表时间：
2016-08-01
影响因子：
6.7
通讯作者：
Benderdour, Mohamed
中科院分区：
文献类型：
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作者：
Benabdoune, Houda;Rondon, Elsa-Patricia;Benderdour, Mohamed
Resolvin D1（RvD 1）是一种omega-3脂肪酸衍生物，在解决炎症，促进组织修复和保持组织完整性方面表现出显着的特性。在这项研究中，我们研究了RvD 1对骨关节炎（OA）病理生理学主要过程的影响。人OA软骨细胞用1 ng/ml白细胞介素-1 β（IL-1 β）或20 μ M 4-羟基壬烯醛（HNE）处理，然后用增加浓度的RvD 1（0-10 μ M）处理或不处理。通过酶免疫测定法测量来自实验性OA犬模型和从我们先前的研究获得的假手术犬的滑液中的RvD 1水平。通过3-（4，5-二甲基-噻唑基）-2，5-二苯基-SH-溴化四唑测定评价细胞活力。通过酶联免疫吸附试验、蛋白质印迹和定量聚合酶链反应测定与炎症、细胞增殖和细胞凋亡相关的参数。用商品化试剂盒测定谷胱甘肽（GSH）。通过Western blot检测有丝分裂原活化蛋白激酶和核因子-κ B（NF-κ B）通路的活化情况，结果显示OA关节滑液中RvD 1的水平高于对照组。在OA人软骨细胞，我们证明，RvD 1是没有毒性高达10 μ M和抑制IL-1 β诱导的环氧合酶2，前列腺素E2，诱导型一氧化氮合酶，一氧化氮和基质金属蛋白酶-13。我们对信号通路的研究表明，RvD 1抑制IL-1 β诱导的NF-κ B B/p65、p38/MAPK和JNK的激活（1/2）。此外，RvD 1防止HNE诱导的细胞凋亡和氧化应激，如通过半胱天冬酶的失活、乳酸脱氢酶释放的抑制、Bcl 2和AKT的水平增加以及GSH所指示的。RvD 1消除了许多已知参与OA发病机制的因素，使其成为预防该疾病的有临床价值的药物。
Resolvin D1 (RvD1), an omega-3 fatty acid derivative, has shown remarkable properties in resolving inflammation, promoting tissue repair and preserving tissue integrity. In this study, we investigated RvD1 effects on major processes involved in osteoarthritis (OA) pathophysiology.Human OA chondrocytes were treated with either 1 ng/ml interleukin-1 beta (IL-1 beta) or 20 mu M 4-hydroxynonenal (HNE), then treated or not with increased concentrations of RvD1 (0-10 mu M). RvD1 levels were measured by enzyme immunoassay in synovial fluids from experimental dog model of OA and sham operated dogs obtained from our previous study. Cell viability was evaluated by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-SH-tetrazolium bromide assay. Parameters related to inflammation, catabolism and apoptosis were determined by enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Glutathione (GSH) was assessed by commercial kit. The activation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-kappa B) pathways was evaluated by Western blot.We showed that RvD1 levels were higher in synovial fluids from OA joint compared to controls. In OA human chondrocytes, we demonstrated that RvD1 was not toxic up to 10 mu M and stifled IL-1 beta-induced cyclooxygenase 2, prostaglandin E2, inducible nitric oxide synthase, nitric oxide, and matrix metalloproteinase-13. Our study of signalling pathways revealed that RvD1 suppressed IL-1 beta-induced activation of NF-kappa B/p65, p38/MAPK and JNK(1/2). Moreover, RvD1 prevented HNE-induced cell apoptosis and oxidative stress, as indicated by inactivation of caspases, inhibition of lactate dehydrogenase release, and increased levels of Bcl2 and AKT, as well as GSH.This is the first in vitro study demonstrating the beneficial effect of RvD1 in OA. That RvD1 abolishing a number of factors known to be involved in OA pathogenesis renders it a clinically valuable agent in prevention of the disease.