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A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis.

一种合成的细胞穿透肝素结合肽,来源于 BMP4,具有抗炎和成软骨功能,用于治疗关节炎。

  • 影响因子:0.0000
  • DOI:10.3390/ijms21124251
  • 作者列表:"Choi DH","Lee D","Jo BS","Park KS","Lee KE","Choi JK","Park YJ","Lee JY","Park YS
  • 发表时间:2020-06-15
Abstract

:We report dual therapeutic effects of a synthetic heparin-binding peptide (HBP) corresponding to residues 15-24 of the heparin binding site in BMP4 in a collagen-induced rheumatic arthritis model (CIA) for the first time. The cell penetrating capacity of HBP led to improved cartilage recovery and anti-inflammatory effects via down-regulation of the iNOS-IFNγ-IL6 signaling pathway in inflamed RAW264.7 cells. Both arthritis and paw swelling scores were significantly improved following HBP injection into CIA model mice. Anti-rheumatic effects were accelerated upon combined treatment with Enbrel® and HBP. Serum IFNγ and IL6 concentrations were markedly reduced following intraperitoneal HBP injection in CIA mice. The anti-rheumatic effects of HBP in mice were similar to those of Enbrel®. Furthermore, the combination of Enbrel® and HBP induced similar anti-rheumatic and anti-inflammatory effects as Enbrel®. We further investigated the effect of HBP on damaged chondrocytes in CIA mice. Regenerative capacity of HBP was confirmed based on increased expression of chondrocyte biomarker genes, including aggrecan, collagen type II and TNFα, in adult human knee chondrocytes. These findings collectively support the utility of our cell-permeable bifunctional HBP with anti-inflammatory and chondrogenic properties as a potential source of therapeutic agents for degenerative inflammatory diseases.

摘要

: 我们报道了在胶原诱导的风湿性关节炎模型 (CIA) 中,与 BMP4 中肝素结合位点残基 15-24 相对应的合成肝素结合肽 (HBP) 的双重治疗作用第一次.HBP 的细胞穿透能力通过下调炎症 RAW264.7 细胞中的 inos-ifn γ-il6 信号通路,改善软骨恢复和抗炎作用。CIA 模型小鼠注射 HBP 后,关节炎和爪肿胀评分均显著改善。Enbrel 联合治疗可加速抗风湿作用®和 HBP。CIA 小鼠腹腔注射 HBP 后,血清 ifn γ 和 IL6 浓度明显降低。HBP 在小鼠中的抗风湿作用与 Enbrel 相似®。此外,Enbrel 的组合®和 HBP 诱导的抗风湿和抗炎作用与 Enbrel 相似®。我们进一步研究了 HBP 对 CIA 小鼠受损软骨细胞的影响。HBP 的再生能力是基于成人膝关节软骨细胞中软骨细胞生物标志物基因 (包括 aggrecan 、 ⅱ 型胶原和 tnf α) 表达增加而证实的。这些发现共同支持我们的具有抗炎和软骨形成特性的细胞渗透性双功能 HBP 作为退行性炎症性疾病治疗药物的潜在来源的效用。

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DOI:10.1080/08916934.2019.1710831
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发表时间:2020-01-29
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作者列表:["Fattah SA","Abdel Fattah MA","Mesbah NM","Saleh SM","Abo-Elmatty DM","Mehanna ET"]

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