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首页> 外文期刊>Arthritis & Rheumatism >Enhancement of intervertebral disc cell senescence by WNT/β-catenin signaling–induced matrix metalloproteinase expression
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Enhancement of intervertebral disc cell senescence by WNT/β-catenin signaling–induced matrix metalloproteinase expression

机译：WNT /β-catenin信号转导诱导的基质金属蛋白酶表达增强椎间盘细胞衰老

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ObjectiveTo determine whether intervertebral disc (IVD) cells express β-catenin and to assess the role of the WNT/β-catenin signaling pathway in cellular senescence and aggrecan synthesis.MethodsThe expression of β-catenin messenger RNA (mRNA) and protein in rat IVD cells was assessed by using several real-time reverse transcription–polymerase chain reaction, Western blot, immunohistochemical, and immunofluorescence analyses. The effect of WNT/β-catenin on nucleus pulposus (NP) cells was examined by transfection experiments, an MTT assay, senescence-associated β-galactosidase staining, a cell cycle analysis, and a transforming growth factor (TGFβ)/bone morphogenetic protein (BMP) pathway–focused microarray analysis.ResultsWe found that β-catenin mRNA and protein were expressed in discs in vivo and that rat NP cells exhibited increased β-catenin mRNA and protein upon stimulation with lithium chloride, a known activator of WNT signaling. LiCl treatment inhibited the proliferation of NP cells in a time- and dose-dependent manner. In addition, there was an increased level of cellular senescence in LiCl-treated cells. Long-term treatment with LiCl induced cell cycle arrest and promoted subsequent apoptosis in NP cells. Activation of WNT/β-catenin signaling also regulated the expression of aggrecan. We also demonstrated that WNT/β-catenin signaling induced the expression of matrix metalloproteinases (MMPs) and TGFβ in NP cells.ConclusionThe activation of WNT/β-catenin signaling promotes cellular senescence and may modulate MMP and TGFβ signaling in NP cells. We hypothesize that the activation of WNT/β-catenin signaling may lead to an increased breakdown of the matrix, thereby promoting IVD degeneration.
机译：目的确定椎间盘（IVD）细胞是否表达β-catenin，并评估WNT /β-catenin信号通路在细胞衰老和聚集蛋白聚糖合成中的作用。方法大鼠IVD中β-cateninMessenger RNA（mRNA）和蛋白质的表达通过使用几种实时逆转录聚合酶链反应，蛋白质印迹，免疫组织化学和免疫荧光分析来评估细胞。通过转染实验，MTT分析，衰老相关的β-半乳糖苷酶染色，细胞周期分析和转化生长因子（TGFβ）/骨形态发生蛋白，研究了WNT /β-catenin对髓核（NP）细胞的影响。结果，我们发现β-cateninmRNA和蛋白在体内的椎间盘中表达，而大鼠NP细胞在被氯化锂（一种已知的WNT信号激活剂）刺激后表现出增加的β-cateninmRNA和蛋白。 LiCl处理以时间和剂量依赖性方式抑制NP细胞的增殖。另外，在LiCl处理的细胞中细胞衰老水平增加。 LiCl的长期治疗诱导细胞周期停滞，并促进随后的NP细胞凋亡。 WNT /β-catenin信号的激活也调节了聚集蛋白聚糖的表达。我们还证明了WNT /β-catenin信号传导诱导了NP细胞中基质金属蛋白酶（MMPs）和TGFβ的表达。我们假设WNT /β-catenin信号的激活可能导致基质分解增加，从而促进IVD变性。

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  • 来源
    《Arthritis & Rheumatism》 |2010年第10期|p.3036-3047|共12页
  • 作者

    Akihiko Hiyama; Daisuke Sakai; Makarand V. Risbud; Masahiro Tanaka; Fumiyuki Arai; Koichiro Abe; Joji Mochida;

  • 作者单位

    Tokai University School of Medicine, Isehara, Japan;

    Tokai University School of Medicine, Isehara, Japan;

    Thomas Jefferson University, Philadelphia, Pennsylvania;

    Tokai University School of Medicine, Isehara, Japan;

    Tokai University School of Medicine, Isehara, Japan;

    Tokai University School of Medicine, Isehara, Japan;

    Tokai University School of Medicine, Isehara, Japan;

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