摘要
目的探讨S100A11-RAGE通过P38MAPK信号转导通路对小鼠骨关节炎软骨细胞肥大和细胞外基质代谢的调控。方法不同浓度的外源性S100A11(0、1.25、2.50、5.00及10.00μg/ml)与小鼠软骨细胞孵育48 h,检测基质金属蛋白酶13(MMP-13)、ADAMTS-5以及Ⅱ型、Ⅹ型胶原蛋白表达,以筛选作用最显著的S100A11浓度。加入不同浓度Anti-P38(0、1.25、2.50、5.00及10.00μg/ml)与小鼠软骨细胞预孵育12 h后,再加入作用最强的外源性S100A11孵育(10μg/ml)48 h,检测MMP-13、ADAMTS-5以及Ⅱ型、Ⅹ型胶原蛋白表达。结果小鼠软骨细胞MMP-13、ADAMTS-5以及Ⅹ型胶原蛋白表达随外源性S100A11浓度的增加而增加,且明显高于对照组;而Ⅱ型胶原蛋白表达随外源性S100A11浓度的增加而减少,且明显低于对照组。加入Anti-P38预处理后,MMP-13、ADAMTS-5以及Ⅹ型胶原蛋白表达均明显低于S100A11单独处理组,而Ⅱ型胶原蛋白表达明显高于S100A11单独处理组。结论外源性S100A11通过与RAGE结合,并经P38MARK信号转导通路诱导软骨细胞肥大和细胞外基质的降解,其机制可能与通过P38MAPK信号转导通路诱导MMP-13、ADAMTS-5以及Ⅹ型胶原蛋白表达,并降低Ⅱ型胶原蛋白表达。
Objective To investigate the regulation of EIOOAll-RAGE on the hypertrophy and extracellular matrix metabolism of chondrocytes by P38MAPK signal pathway in mice. Methods Different concentrations of exogenous SIOOAll and cartilage cells were incubated for 48 h. Expressions of MMP-13, ADAMTS-5, type Ⅱ and type X collagen were detected by PCR, Westem Blot and immunohistochemistry, respectively. Anti-P38 and cartilage cells were incubated for 12 h, and then incubated 48 h after exogenous S100A11 was added. Expressions of MMP-13, ADAMTS-5, type Ⅱ and type X collagen were detected. Results The expression of MMP-13, ADAMTS-5 and type X collagen of cartilage cells increased with the increase of the concentration of exogenous S100A11, and was significantly higher than that of the control group. The expression of type lI collagen decreased with the increase of the concentration of exogenous S100A1, and was significantly lower than that of the control group. After the addition of Anti-P38, the expressions of MMP-13, ADAMTS-5 and type X collagen were significantly lower than that of S100A11 alone treatment group, and the expression of type Ⅱ collagen was significantly higher than that of SIOOA 11 alone treatment group. Conclusions S100A11-RAGE can regulate the hypertrophy and extracellular matrixdegradation of chondrocytes in mice, and the mechanism may be related to the induced MMP-13, ADAMTS-5 and type X collagen expression and reduce type Ⅱ collagen expression through the P38 MAPK signal pathway.
出处
《中国现代医学杂志》
CAS
北大核心
2016年第16期6-11,共6页
China Journal of Modern Medicine
