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Evaluation of the post-treatment anti-inflammatory capacity of osteoarthritic chondrocytes: An in vitro study using baicalein.
Regenerative Therapy ( IF 3.4 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.reth.2020.02.002
Chang-Chin Wu , Yi-Ru Chen , Dai-Hua Lu , Li-Ho Hsu , Kai-Chiang Yang , Shoichiro Sumi

Introduction

Targeting inflammatory cascades is considered a promising way to prevent knee osteoarthritis (OA) progression. In terms of down-regulating the expression of inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and matrix metalloproteinases (MMPs), pre-treatment with the flavonoid baicalein reportedly protects articular chondrocytes against the cytotoxicity of IL-1β. However, the benefits of post-treatment baicalein on osteoarthritic chondrocytes are not fully elucidated.

Methods

In this study, primary human chondrocytes were stimulated with IL-1β prior to baicalein application to evaluate the therapeutic effect of post-treatment.

Results

Post-treatment baicalein alleviated cell death and partially restored mitochondrial viability, while the senescence-associated secretory phenotype was not improved in IL-1β-stimulated chondrocytes. Post-treatment baicalein down-regulated the expressions of IL-1β, tumor necrosis factor-alpha, MMP-3, MMP-9, and MMP-13 mRNA as well as the protein production in stimulated cells. Even so, the levels of these factors were relative higher than those in un-treated chondrocytes. Moreover, iNOS, IL-6, IL-8, and COL1A1 expressions were consistently high, and IL-10 protein synthesis steadily increased in IL-1β-treated chondrocytes under baicalein treated status. Moreover, Western blot analyses showed that post-treatment baicalein suppressed nuclear factor kappa-light-chain-enhancer of activated B cells and p50 production while downstream cyclooxygenase-2 was still highly expressed.

Conclusion

Baicalein post-treatment to osteoarthritic chondrocytes had a minor benefit to the homeostasis of cartilaginous extracellular matrix.



中文翻译:


骨关节炎软骨细胞治疗后抗炎能力的评估:使用黄芩素的体外研究。


 介绍


针对炎症级联反应被认为是预防膝骨关节炎(OA)进展的一种有前途的方法。据报道,在下调诱导型一氧化氮合酶( iNOS )、白细胞介素 ( IL ) -6基质金属蛋白酶( MMP ) 的表达方面,黄酮类黄芩素预处理可保护关节软骨细胞免受 IL-1β 的细胞毒性。然而,治疗后黄芩素对骨关节炎软骨细胞的益处尚未完全阐明。

 方法


在这项研究中,在应用黄芩素之前用 IL-1β 刺激原代人软骨细胞,以评估治疗后的治疗效果。

 结果


治疗后黄芩素减轻了细胞死亡并部分恢复了线粒体活力,而 IL-1β 刺激的软骨细胞中与衰老相关的分泌表型并未得到改善。治疗后黄芩素下调IL-1β肿瘤坏死因子-αMMP-3MMP-9MMP -13 mRNA 的表达以及受刺激细胞中的蛋白质产生。即便如此,这些因子的水平相对高于未经处理的软骨细胞。此外,在黄芩素处理状态下,IL-1β处理的软骨细胞中iNOSIL-6、IL-8COL1A1的表达持续较高,IL-10蛋白合成稳定增加。此外,蛋白质印迹分析表明,治疗后黄芩素抑制了活化 B 细胞的核因子 kappa-轻链增强子和 p50 的产生,而下游环加氧酶-2 仍然高度表达。

 结论


黄芩素对骨关节炎软骨细胞进行后处理对软骨细胞外基质的稳态有较小的益处。

更新日期:2020-02-24
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