Regulated factors of NF-kB activity in synovial fibroblasts by repetitive mechanical stretch

重复机械拉伸对滑膜成纤维细胞NF-kB活性的调节因素

• 批准号: 17592095
• 负责人: KAWAKAMI Tetsuji
• 金额: $ 2.24万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17592095/
• 关键词: Temporomandibular joint (TMJ); Cyclooxygenase-2 (COX-2); Mechanical stretch; Svnovial fibroblasts; Nuclear factor-κB (NF-κB); 培養滑膜細胞(HIG-82); Nuclear factorκB (NF-κB); Nuclear factor κB(NF-κB)

It is proposed that synovial inflammation mediated by induced cyclooxygenase-2 (COX-2) has important roles in the onset of temporomandibular joint (TMJ) pain. However, we have little knowledge about the pathophysiology of TMJ pain. In our previous studies, we have demonstrated that COX-2 and the transcription factor nuclear factor κB (NF-κB) were induced in lapine synovial fibroblast cells (HIG-82) by excessive mechanical stretch (140% peak to peak). In this study, we examined whether COX-2 and NF-κB were induced in HIG-82 cells by repetitive and weak stretch (120% peak to peak) such as bruxism and clenching. Moreover, we examined regulated factors of NF-κB activity induced by mechanical stretch in HIG-82 cells.Reporter gene assay showed that NF-κB activity in HIG-82 transiently increased according to the increase of stretching periods and decreased gradually, suggesting that NF-κB activity in HIG-82 with dynamic weak repetitive stretch was significantly higher than static excessive st … More retch. Similarly, COX-2 protein induced by repetitive mechanical stress transiently increased. This suggested that synovial inflammation due to repetitive motion might lead to TMJ pain.To examine regulated factors of NF-κB activity induced by mechanical stretch in HIG-82 cells, the cells were incubated for 1 hour with some COX-2 inhibitors (BAY11-7085 (2μM), curcumin (10〜40μM), MG132 (2μM), PDTC (5μM), and SP600125 (5μM) ) prior to cycling stretch. NF-κB activity in response to stretching is significantly suppressed by COX-2 inhibitor (curcumin, BAY11-7085, MG132 and PDTC). Similarly, COX-2 inhibitors suppressed induction of COX-2 in response to repetitive stretch. Among them, curcumin, a major component of food spice turmeric, is known for anti-inflammatory and antioxidant properties. This suggested that pharmacotherapy using COX-2 inhibitors (e.g. curcumin) could be applied to a new treatment for TMD.The present study suggested that synovial inflammation due to repetitive motion, such as bruxism and clenching, might lead to TMJ pain, and that inflammation of synoviocyte was able to suppress by pretreatment of COX-2 inhibitors. Less

有人提出，诱导环氧合酶-2 (COX-2) 介导的滑膜炎症在颞下颌关节 (TMJ) 疼痛的发生中起重要作用。然而，我们对颞下颌关节疼痛的病理生理学知之甚少。在我们之前的研究中，我们已经证明，过度机械拉伸（140% 峰峰值）会在兔滑膜成纤维细胞 (HIG-82) 中诱导 COX-2 和转录因子核因子 κB (NF-κB)。在本研究中，我们检查了重复性和弱拉伸（120% 峰峰值）（例如磨牙症和咬紧牙关）是否会在 HIG-82 细胞中诱导 COX-2 和 NF-κB。此外，我们还检测了HIG-82细胞中机械拉伸诱导的NF-κB活性的调节因素。报告基因检测显示，HIG-82中的NF-κB活性随着拉伸周期的增加而短暂增加，并逐渐下降，表明动态弱重复拉伸的HIG-82中NF-κB活性显着高于静态过度拉伸。同样，重复机械应力诱导的 COX-2 蛋白短暂增加。这表明重复运动引起的滑膜炎症可能导致颞下颌关节疼痛。为了检查HIG-82细胞中机械拉伸诱导的NF-κB活性的调节因素，将细胞与一些COX-2抑制剂（BAY11-7085（2μM）、姜黄素（10〜40μM）、MG132（2μM）、PDTC（5μM）和 SP600125 (5μM) ) 在循环拉伸之前。 COX-2 抑制剂（姜黄素、BAY11-7085、MG132 和 PDTC）显着抑制拉伸反应中的 NF-κB 活性。同样，COX-2 抑制剂可抑制重复拉伸时 COX-2 的诱导。其中，姜黄素是食品香料姜黄的主要成分，以抗炎和抗氧化特性而闻名。这表明使用COX-2抑制剂（例如姜黄素）的药物疗法可以应用于治疗TMD的新方法。本研究表明，由于重复运动（例如磨牙和咬紧牙关）引起的滑膜炎症可能会导致颞下颌关节疼痛，而滑膜细胞的炎症可以通过COX-2抑制剂的预处理来抑制。较少的