Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1 induced inflammation in synoviocytes in vitro
Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1 induced inflammation in synoviocytes in vitro
复制标题
编码 CrmA 的透明质酸-壳聚糖纳米粒子可在体外减轻白细胞介素 1β 诱导的滑膜细胞炎症。
DOI：
10.3892/ijmm.2018.3997
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发表时间：
2019-02-01
影响因子：
5.4
通讯作者：
Zhou, Pang-Hu
中科院分区：
文献类型：
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作者：
Qiu, Bo;Xu, Xiong-Feng;Zhou, Pang-Hu
骨关节炎（Osteoarthritis，OA）是一种常见的退行性关节疾病，其特征在于滑膜细胞的炎症和软骨的降解。在本研究中，透明质酸/壳聚糖（HA/CS）纳米粒作为载体的基因治疗OA，和细胞因子反应调节剂A（CrmA）pDNA作为目标基因的建议。制备了HA/CS/pCrmA纳米粒子，并对其性质进行了研究。纳米颗粒是球形的，并且在HA：CS重量比为1：4的情况下获得最小尺寸。释放分析显示在29天内持续释放。pDNA与HA/CS纳米颗粒完全结合，并且HA/CS纳米颗粒保护pDNA免于降解。随后，将HA/CS/pDNA纳米颗粒转染大鼠滑膜细胞，结果表明HA/CS纳米颗粒能够提高pDNA的转染能力。另外使用MTS试验检测HA/CS/pDNA纳米颗粒的细胞毒性，以确保HA/CS纳米颗粒是安全的载体。为了进一步研究HA/CS/pCrmA纳米颗粒对OA滑膜细胞的影响，在基因和蛋白表达水平上检测MMP-3和MMP-13基因表达水平。这些结果表明HA/CS/pCrmA纳米颗粒减弱了滑膜细胞中白介素-1介导的炎症。结论：HA/CS/pCrmA纳米粒有望成为治疗骨关节炎的新途径。
Osteoarthritis (OA) is a common degenerative joint disease characterized by inflammation of synoviocytes and degradation of cartilage. In the present study, hyaluronic acid/chitosan (HA/CS) nanoparticles were used as a vehicle for gene therapy of OA, and the cytokine response modifier A (CrmA) pDNA was proposed as the target gene. The HA/CS/pCrmA nanoparticles were prepared and the characteristics of the nanoparticles were examined. The nanoparticles were spherical, and the smallest size was obtained with the HA:CS weight ratio of 1:4. The release analysis exhibited a constant release over 29 days. The pDNA was completely combined with HA/CS nanoparticles and the HA/CS nanoparticles protected pDNA from degradation. Subsequently, rat synoviocytes were transfected with HA/CS/pDNA nanoparticles, and the results demonstrated that the HA/CS nanoparticles were able to improve the transfection capacity of pDNA. The cytotoxicity of the HA/CS/pDNA nanoparticles was additionally detected using a MTS assay to ensure that the HA/CS nanoparticle was a safe carrier. To additionally investigate the effects of HA/CS/pCrmA nanoparticles on synoviocytes in OA, the MMP-3 and MMP-13 gene expression levels were detected at the gene and protein expression levels. These results indicated that the HA/CS/pCrmA nanoparticles attenuated interleukin-1-mediated inflammation in synoviocytes. It was concluded that the HA/CS/pCrmA nanoparticles may provide a novel approach to the treatment of OA.