Diacerein has a weak effect on the catabolic pathway of human osteoarthritis synovial fibroblast -: comparison to its effects on osteoarthritic chondrocytes
Diacerein has a weak effect on the catabolic pathway of human osteoarthritis synovial fibroblast -: comparison to its effects on osteoarthritic chondrocytes
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DOI：
10.1093/rheumatology/ken116
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发表时间：
2008-05-01
期刊：
影响因子：
5.5
通讯作者：
Largo, R.
中科院分区：
文献类型：
--
作者：
Alvarez-Soria, M. A.;Herrero-Beaumont, G.;Largo, R.
目标。滑膜细胞在导致骨关节炎结构损伤的炎症反应中起着至关重要的作用。我们的目的是评估双乙醇胺和非甾体抗炎药对滑膜细胞的细胞反应的影响，这些细胞反应与关节软骨的炎症和结构完整性有关。研究了双乙醇胺、塞来昔布、双氯芬酸、美洛昔康和消炎痛对骨性关节炎滑膜细胞和软骨细胞前列腺素E_2(PG-E_2)产生、环氧合酶-2(COX-2)蛋白表达、亚硝酸盐水平、基质金属蛋白酶-1和-13的表达以及核因子-kappaB(NF-kappa B)活化的影响。Dacerein和NSAIDs均可抑制IL-1β刺激的滑膜细胞和软骨细胞的NF-kappaB活化，但滑膜细胞中的消炎痛除外。双乙醇胺进一步增加IL-β1刺激的滑膜细胞COX-2蛋白表达和PGE2合成，而对刺激的软骨细胞无影响。NSAIDs在两种细胞中的PGE2释放几乎达到基础水平，令人惊讶的是，这些药物还降低了滑膜细胞和软骨细胞中COX-2的蛋白表达。在结构介质方面，双乙酸乙酯降低了滑膜细胞中基质金属蛋白酶-13的水平，但不改变基质金属蛋白酶-1的存在。非甾体抗炎药诱导两种细胞的基质金属蛋白酶-1水平和软骨细胞基质金属蛋白酶-13水平均显著升高。Diacerein似乎并没有减少而是增加了滑膜细胞中的炎症介质，但它并不总体上影响软骨细胞的炎症情况。
Objectives. Synoviocytes play a crucial role in the inflammatory response leading to structural damage in OA. Our aim was to assess the effects of diacerein and NSAIDs on cellular responses of synoviocytes associated with inflammation and structural integrity of cartilage in OA.Methods. The effects of diacerein, celecoxib, diclofenac, meloxicam and indomethacin on prostaglandin (PG) E2 production, cyclo-oxygenase-2 (COX-2) protein expression, nitrite levels, presence of MMP-1 and -13, and activation of nuclear factor-kappa B (NF-kappa B) were studied on stimulated OA synoviocytes and chondrocytes.Results. Diacerein and NSAIDs inhibited IL-1 beta-stimulated NF-kappa B activation in synoviocytes and chondrocytes except indomethacin in synoviocytes. Diacerein further increased COX-2 protein expression and PGE2 synthesis in synoviocytes stimulated with IL-beta 1, while no effect was observed on stimulated chondrocytes. NSAIDs diminished until almost basal levels PGE2 release in both cells and, surprisingly, these drugs also diminished COX-2 protein expression both in synoviocytes and chondrocytes. With regard to structural mediators, diacerein decreased MMP-13 levels in synoviocytes but did not modify MMP-1 presence. NSAIDs induced a significant increase in MMP-1 levels in both cell types and in MMP-13 levels in chondrocytes.Conclusions. Diacerein does not seem to reduce but rather increase inflammatory mediators in synoviocytes, while it does not overall affect chondrocyte inflammatory profile.