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首页> 外文期刊>Cellular Signalling >MiR-193b modulates osteoarthritis progression through targeting ST3GAL4 via sialylation of CD44 and NF-kappa B pathway
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MiR-193b modulates osteoarthritis progression through targeting ST3GAL4 via sialylation of CD44 and NF-kappa B pathway

机译：miR-193b通过CD44和NF-κB途径的唾液化通过靶向ST3GAL4来调节骨关节炎进展

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摘要

Osteoarthritis (OA) is a worldwide epidemic and debilitating disease. It is urgent to explore the potential molecular mechanisms of OA which has crucial roles in the treatment strategy. As a post-translational modification, sialylation mediates the progression of OA. In current study, differential expression of sialyltransferases (STs) in normal and OA cartilage tissues is detected. The ST3GAL4 expression is significantly increased and positively associated with modified Mankin's score in OA tissue. Alteration of ST3GAL4 respectively mediates the degradation of extracellular mechanisms (ECM), apoptosis and proliferation in chondrocytes. Additionally, miR-193b is identified as a direct regulatory target of ST3GAL4. Functional analysis shows that modulation of ST3GAL4 could be reversed by miR-193b. Over-expression ST3GAL4 modifies CD44 sialylation. Finally, sialylated CD44 reduces the binding capacity to lubricin and mediates the activity of the NF-kappa B pathway. Collectively, these researches indicate that miR-193b/ST3GAL4 axis impacts OA progression by regulating CD44 sialylation via NF-kappa B pathway. Our researches propose a precise molecular mechanism and provide a prospective therapeutic target in OA.
机译：骨关节炎（OA）是一种全球性的流行性疾病。OA在治疗策略中起着至关重要的作用，因此迫切需要探索其潜在的分子机制。作为翻译后修饰，唾液酸化介导OA的进展。在目前的研究中，检测到唾液酸转移酶（STs）在正常和OA软骨组织中的差异表达。ST3GAL4表达显著增加，并与OA组织中改良的曼金评分呈正相关。ST3GAL4的改变分别介导软骨细胞的细胞外机制（ECM）降解、凋亡和增殖。此外，miR-193b被确定为ST3GAL4的直接调控靶点。功能分析表明，miR-193b可以逆转ST3GAL4的调节。ST3GAL4的过度表达修饰CD44唾液酸化。最后，唾液酸化CD44降低了与润滑素的结合能力，并介导了NF-κB途径的活性。总之，这些研究表明，miR-193b/ST3GAL4轴通过NF-κB途径调节CD44唾液酸化，从而影响OA的进展。我们的研究提出了一个精确的分子机制，为OA提供了一个有前景的治疗靶点。

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  • 来源
    《Cellular Signalling》 |2020年第1期|共10页
  • 作者

    Wang Tianfu; Hao Zhiyu; Liu Changcheng; Yuan Lebin; Li Li; Yin Menghong; Li Qing; Qi Zhiming; Wang Zi;

  • 作者单位

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Med Univ Dept Imaging &

    Nucl Med Hosp 2 Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

    Dalian Municipal Cent Hosp Dept Sports Med 826 Southwest Rd Dalian 116033 Liaoning Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞形态学;
  • 关键词

    Osteoarthritis; miR-193b; ST3GAL4; CD44; NF-kappa B signaling pathway;

    机译：骨关节炎;miR-193b;st3gal4;cd44;nf-kappa发信号通路;

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