Cyclic Tensile Strain Upregulates Pro-Inflammatory Cytokine Expression Via FAK-MAPK Signaling in Chondrocytes
Cyclic Tensile Strain Upregulates Pro-Inflammatory Cytokine Expression Via FAK-MAPK Signaling in Chondrocytes
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DOI：
10.1007/s10753-018-0805-8
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发表时间：
2018-05
期刊：
影响因子：
5.1
通讯作者：
Makoto Yanoshita;N. Hirose;Yuki Okamoto;C. Sumi;Mami Takano;Sayuri Nishiyama;Yuki Asakawa-Tanne;Kayo Horie;Azusa Onishi;Y. Yamauchi;T. Mitsuyoshi;R. Kunimatsu;K. Tanimoto
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文献类型：
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作者：
Makoto Yanoshita;N. Hirose;Yuki Okamoto;C. Sumi;Mami Takano;Sayuri Nishiyama;Yuki Asakawa-Tanne;Kayo Horie;Azusa Onishi;Y. Yamauchi;T. Mitsuyoshi;R. Kunimatsu;K. Tanimoto
过度的机械刺激被认为是软骨细胞破坏的一个重要因素。粘着斑激酶（FAK）是一种非受体酪氨酸激酶，与许多不同的信号蛋白相关。机械刺激下FAK在软骨细胞中的作用尚不清楚。本研究探讨了FAK在机械信号转导中的作用以及周期性拉伸应变（CTS）诱导炎症相关因子表达的机制。用FAK抑制剂使小鼠ATDC 5软骨形成细胞经受0.5Hz至10%细胞伸长的CTS。应用CTS和FAK抑制剂后，使用实时RT-PCR检测编码考克斯-2、IL-1β和TNF-α的基因的表达。通过蛋白质印迹分析p-38、ERK和JNK的磷酸化。用蛋白质印迹法比较用FAK、p-38、ERK和JNK抑制剂预处理后考克斯-2表达的差异。我们发现CTS增加了编码考克斯-2、IL-1β和TNF-α的基因的表达，并激活了FAK、p-38、ERK和JNK的磷酸化。用FAK抑制剂预处理2 h可降低由CTS相关炎症诱导的编码考克斯-2、IL-1β和TNF-α的基因表达，并降低FAK、p-38、ERK和JNK的磷酸化。用FAK、p-38、ERK和JNK抑制剂预处理显著抑制考克斯-2和IL-1β蛋白表达。总之，FAK似乎通过CTSviaMAPK途径调节软骨细胞中的炎症。
AbstractExcessive mechanical stimulation is considered an important factor in the destruction of chondrocytes. Focal adhesion kinase (FAK) is non-receptor tyrosine kinase related to a number of different signaling proteins. Little is known about the function of FAK in chondrocytes under mechanical stimulation. In the present study, we investigated the function of FAK in mechanical signal transduction and the mechanism through which cyclic tensile strain (CTS) induces expression of inflammation-related factors. Mouse ATDC5 chondrogenic cells were subjected to CTS of 0.5 Hz to 10% cell elongation with an FAK inhibitor. The expression of genes encoding COX-2, IL-1β, and TNF-α was examined using real-time RT-PCR after CTS application with FAK inhibitor. Phosphorylation of p-38, ERK, and JNK was analyzed by Western blotting. Differences in COX-2 expression following pretreatment with FAK, p-38, ERK, and JNK inhibitors were compared by Western blotting. We found that CTS increased the expression of genes encoding COX-2, IL-1β, and TNF-α and activated the phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with an FAK inhibitor for 2 h reduced the expression of genes encoding COX-2, IL-1β, and TNF-α induced by CTS-associated inflammation and decreased phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with FAK, p-38, ERK, and JNK inhibitors markedly suppressed COX-2 and IL-1β protein expression. In conclusion, FAK appears to regulate inflammation in chondrocytes under CTSviaMAPK pathways.