Interleukin-6 Promotes Proliferation but Inhibits Tenogenic Differentiation via the Janus Kinase/Signal Transducers and Activators of Transcription 3 (JAK/STAT3) Pathway in Tendon-Derived Stem Cells.
Interleukin-6 Promotes Proliferation but Inhibits Tenogenic Differentiation via the Janus Kinase/Signal Transducers and Activators of Transcription 3 (JAK/STAT3) Pathway in Tendon-Derived Stem Cells.
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Interleukin-6 通过肌腱衍生干细胞中的 Janus 激酶/信号转导子和转录激活剂 3 (JAK/STAT3) 途径促进增殖，但抑制肌腱分化。
DOI：
10.12659/msm.908802
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发表时间：
2018-03-16
期刊：
影响因子：
--
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Chen S;Deng G;Li K;Zheng H;Wang G;Yu B;Zhang K
以前的研究表明，肌腱来源的干细胞（TDSCs）是重要的愈合细胞，并且在损伤的肌腱中抗炎细胞因子IL-6的mRNA表达显著上调。本研究旨在探讨IL-6对体外培养的TDSC的影响。从SD大鼠跟腱分离的TDSCs与不同浓度的IL-6共培养。采用细胞增殖、细胞周期分析、实时荧光定量PCR、蛋白质印迹分析和统计学分析等方法进行研究。结果表明，IL-6可显著增强TDSC的增殖能力，诱导TDSC细胞周期活化，由G1期向G2/M期转变。然而，IL-6处理强烈抑制TDSC中的硬化蛋白、胶原1、腱调节蛋白、胶原3、早期生长反应蛋白1、核心蛋白聚糖、光蛋白聚糖、双糖链蛋白聚糖和纤维调节蛋白的基因表达。它还强烈抑制肌腱细胞标志物如巩膜轴、胶原蛋白1、胶原蛋白3和腱调节蛋白的蛋白质表达。IL-6处理强烈激活TDSC中的JAK/Stat 3信号通路。JAK/Stat 3信号通路抑制剂WP1066可阻断IL-6对TDSC的作用。这些结果表明，IL-6在体外对TDSC具有双重作用：通过JAK/Stat 3途径强烈促进其增殖，但抑制其向肌腱分化。
Previous studies demonstrated that tendon-derived stem cells (TDSCs) were vital healing cells and that mRNA expression of anti-inflammatory cytokine IL-6 was significantly upregulated in injured tendons. The aim of the present study was to investigate the effects of IL-6 on the TDSCs in vitro. TDSCs isolated from the Achilles tendons in SD rats were co-cultured with various concentrations of IL-6. Cell proliferation, cell cycle analysis, quantitative real-time PCR, western blotting analysis, and statistical analysis were used in the study. The result showed that IL-6 strongly increased proliferation capability, and induced cell cycle activation and transition into G2/M phase from G1 phase in TDSCs. However, IL-6 treatment strongly inhibited gene expression of Scleraxis, Collagen 1, Tenomodulin, Collagen 3, Early Growth Response Protein 1, Decorin, Lumican, Biglycan and Fibromodulin in TDSCs. It also strongly inhibited protein expression of tendon cell markers like scleraxis, collagen 1, collagen 3, and tenomodulin. IL-6 treatment strongly activated the JAK/Stat3 signaling pathway in TDSCs. Furthermore, WP1066, a JAK/Stat3 signaling pathway inhibitor, abrogated the effects of IL-6 on TDSCs. These findings indicated that IL-6 might exert dual effects on TDSCs in vitro: strongly enhancing their proliferation but inhibiting their tenogenic differentiation via the JAK/Stat3 pathway.
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