Comparison of Anti-Inflammatory Analgesics for Mechanical Stress-induced Inflammation in a Human Synovial Sarcoma Cell Line

Haruna Shirako, Yuko Udaka, Akiko Sasaki, S. Nakamura, Mayumi Tsuji, Y. Kiuchi
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Abstract

: Osteoarthritis is a complicated clinical condition affected by age, mechanical stress, cartilage hypertrophy, cytokines, and genetic predisposition. In this study, we compared the effects of various anti-inflammatory analgesics on mechanical stress-induced inflammation in a synovial sarcoma cell line ( SW982 cells ) . SW982 cells exposed to mechanical stress by shaking with hydroxyapatite-simulating bone chips were treated with acetaminophen, ketoprofen, triamcinolone acetonide, celecoxib, or neurotrophin for 48 hr. The expression of integrin α 5 β 1 receptor, observed in fibroblasts and synovium, was evaluated. Levels of the transcription factor, nuclear factor- κ B, the inflammatory cytokine, tumor necrosis factor- α , the proteolytic enzyme, matrix metalloproteinase-3, and prostaglandin E 2 , which is associated with pain and arachidonate cascade product levels, were measured by ELISA. The expression of integrin α 5 β 1 was significantly increased by mechanical stress. Activation of nuclear factor- κ B by mechanical stress was significantly suppressed by celecoxib only. Mechanical stress-induced increases in tumor necrosis factor- α and matrix metalloproteinase-3 levels were significantly suppressed by acetaminophen, triamcinolone acetonide, and neurotrophin. mechanical stress-induced increase in prostaglandin E 2 levels was significantly suppressed by acetaminophen, ketoprofen, and celecoxib. 1, a membrane receptor protein that binds to fibronectin and the extracellular matrix, and is involved in cell proliferation, differentiation, and neovascularization in osteoarthritis, was significantly upregulated. Following evaluation using this model, acetaminophen was found to possess anti-inflammatory, analgesic, and joint-destruction suppression properties. This drug may, therefore, have applications in the treatment of mechanical stress-induced inflammation.
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抗炎镇痛药治疗人滑膜肉瘤细胞系机械应力诱导炎症的比较
骨关节炎是一种复杂的临床疾病,受年龄、机械应力、软骨肥大、细胞因子和遗传易感性的影响。在这项研究中,我们比较了各种抗炎镇痛药对滑膜肉瘤细胞系(SW982细胞)机械应力诱导炎症的影响。用羟基磷灰石模拟骨片震荡暴露于机械应力下的SW982细胞,分别用对乙酰氨基酚、酮洛芬、曲安奈德、塞来昔布或神经营养因子处理48小时。观察成纤维细胞和滑膜中整合素α 5 β 1受体的表达。采用ELISA法检测与疼痛相关的转录因子、核因子- κ B、炎症细胞因子、肿瘤坏死因子- α、蛋白水解酶、基质金属蛋白酶-3、前列腺素e2水平及花生四烯酸级联产物水平。机械应力显著提高了整合素α 5 β 1的表达。仅塞来昔布可显著抑制机械应力对核因子- κ B的激活。对乙酰氨基酚、曲安奈德和神经营养因子显著抑制机械应力诱导的肿瘤坏死因子- α和基质金属蛋白酶-3水平升高。对乙酰氨基酚、酮洛芬和塞来昔布显著抑制机械应力引起的前列腺素e2水平升高。1是一种结合纤维连接蛋白和细胞外基质的膜受体蛋白,参与骨关节炎的细胞增殖、分化和新生血管形成,该蛋白显著上调。在使用该模型进行评估后,发现对乙酰氨基酚具有抗炎、镇痛和抑制关节破坏的特性。因此,这种药物可能在治疗机械应力引起的炎症方面有应用。
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