Pressure and inflammatory stimulation induced increase of cadherin-11 is mediated by PI3K/Akt pathway in synovial fibroblasts from temporomandibular joint
Pressure and inflammatory stimulation induced increase of cadherin-11 is mediated by PI3K/Akt pathway in synovial fibroblasts from temporomandibular joint
复制标题
压力和炎症刺激诱导的 cadherin-11 增加是由 PI3K/Akt 通路介导的颞下颌关节滑膜成纤维细胞
DOI：
10.1016/j.joca.2013.07.015
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发表时间：
2013
影响因子：
7
通讯作者：
Gu Zhiyuan
中科院分区：
文献类型：
--
作者：
Wu Mengjie;Xu Ting;Zhou Yiqun;Lu Haiping;Gu Zhiyuan
方法分离大鼠颞下颌关节（TMJ）滑膜成纤维细胞（SFs），分别给予30、60、90、120 kPa的静水压力（HP）和肿瘤坏死因子-α（TNF-α）处理12、12、14、16、18、18、19、19、20、20、30、21、22、32、34、24、36、38、38、40、40、50、60、60、90、120 kPa，观察机械刺激和炎症刺激对SFs中钙粘蛋白11（cadherin-11）表达的影响。24、48和72 h。免疫荧光显微镜观察cadherin-11的定位，实时定量PCR和Western blot检测cadherin-11的表达。结果HP和TNF-α刺激后，SF的细胞-细胞接触部位钙粘蛋白-11（cadherin-11）表达增加。cadherin-11的mRNA和蛋白表达与HP的严重程度和TNF-α治疗的持续时间呈正相关。用PI 3 K抑制剂LY 294002治疗可以减弱压力或炎症细胞因子诱导的钙粘蛋白-11，VEGF-D，和FGF-2在mRNA和蛋白水平上的表达。11可能在机械负荷和炎症刺激后的SFs中发挥重要作用。此外，PI 3 K/Akt信号通路与压力或炎症诱导的钙粘蛋白-11表达有关，可能参与了颞下颌关节疾病的发病机制。
ObjectiveThe goal of the study was to investigate the expression of cadherin-11 in synovial fibroblasts (SFs) under mechanical or inflammatory stimuli, and its potential relationship with PI3K/Akt signaling pathway.MethodsSFs separated from rat temporomandibular joint (TMJ) were treated with hydrostatic pressures (HP) of 30, 60, 90, and 120 kPa, as well as tumor necrosis factor-α (TNF-α) for 12, 24, 48, and 72 h. The location of cadherin-11 was observed by immunofluorescence microscopy, and its expression was detected by real-time PCR and Western blot. We also studied the activation of PI3K/Akt signaling pathway in SFs with HP or TNF-α stimulation.ResultsThe results showed that increased expression of cadherin-11 could be found in the cell–cell contact site of SFs in response to HP and inflammatory stimulation. The mRNA and protein expression of cadherin-11 was positively correlated with the intensity of HP and the duration time of TNF-α treatment. Increased expression of vascular endothelial growth factor-D (VEGF-D) and activation of Akt were also found. Treatment with PI3K inhibitor LY294002 attenuated the pressure or inflammatory cytokine induction increases of cadherin-11, VEGF-D, and FGF-2 both in mRNA and protein levels.ConclusionsThese findings suggest that cadherin-11 may play important roles in SFs following exposure to mechanical loading and inflammatory stimulation. In addition, PI3K/Akt pathway was associated with pressure or inflammation-induced cadherin-11 expression, which may involve in the pathogenesis of temporomandibular diseases.