In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis.
In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis.
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DOI：
10.1016/j.joca.2012.08.011
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发表时间：
2012-12
影响因子：
7
通讯作者：
Bertone, A. L.
中科院分区：
文献类型：
--
作者：
Santangelo, K. S.;Nuovo, G. J.;Bertone, A. L.
关键词：
在原发性骨关节炎模型中，通过基于RNA干扰的转录减少或受体阻断来减少白细胞介素-1 β（IL-1β）信号传导，并量化其他介质的转录表达变化。在第60天注射病毒载体（N=4/处理组/日期）后，在120和180日龄时采集Hartley豚鼠的膝关节。两组接受含有敲低序列的腺相关病毒血清型5载体（TV）或编码IL-1受体拮抗剂蛋白的腺病毒载体（Ad-IRAP）;治疗与给予相应载体对照的对侧膝关节进行对比。第三组评估了TV相对于仅注射生理盐水的膝关节。将软骨病和免疫组织化学结果与未处理豚鼠进行比较。使用比较CT（2-ΔΔCT）方法计算软骨中的转录物表达水平，并使用Tukey 95%置信区间通过单因素ANOVA进行成对比较分析。在两个收获日期均确认了载体转导。相对于载体对照，TV和Ad-IRAP显著降低IL-1β。炎症介质[肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、干扰素-γ（IFN-γ）]和分解代谢基质金属蛋白酶13（MMP 13）也减少，而合成代谢转化生长因子-β1（TGF-β1）增加。与生理盐水相比，TV也降低了IL-1β，MMP 13降低，TGF-β1升高; TNF-α、IL-8和IFN-γ一过性升高。这项工作证实，通过任何一种方法都可以减少IL-1β信号传导，导致三种炎症介质和一种分解代谢剂的表达减少，以及一种合成代谢分子的表达增加。因此，有证据表明IL-1β在体内自发性骨关节炎中发挥作用，并且这些翻译工具可提供有益的疾病修饰。
Diminish interleukin-1β (IL-1β) signaling in a model of primary osteoarthritis by RNA interference-based transcript reduction or receptor blockade, and quantify changes incurred on transcript expression of additional mediators. Knees of Hartley guinea pigs were collected at 120 and 180 days of age following injection with viral vectors (N=4/treatment group/date) at 60 days. Two groups received either adeno-associated viral serotype 5 vector containing a knockdown sequence (TV), or adenoviral vector encoding for IL-1 receptor antagonist protein (Ad-IRAP); treatments were contrasted with opposite knees administered corresponding vector controls. A third group evaluated TV relative to saline-only injected knees. Chondropathy and immunohistochemistry findings were compared to untreated guinea pigs. Transcript expression levels in cartilage were calculated using the comparative CT (2−ΔΔCT) method and analyzed by one-way ANOVA with pairwise comparisons using Tukey 95% confidence intervals. Vector transduction was confirmed at both harvest dates. TV and Ad-IRAP, relative to vector controls, significantly decreased IL-1β. Inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ)], and catabolic matrix metalloproteinase 13 (MMP13) were also decreased, while anabolic transforming growth factor-β1 (TGF-β1) was increased. IL-1β was also decreased by TV versus saline, with a decrease in MMP13 and increase TGF-β1; TNF-α, IL-8, and IFN-γ were transiently increased. This work confirmed that a reduction in IL-1β signaling was accomplished by either method, resulting in decreased expression of three inflammatory mediators and one catabolic agent, and increased expression of an anabolic molecule. Thus, evidence is provided that IL-1β serves a role in vivo in spontaneous osteoarthritis and that these translational tools may provide beneficial disease modification.
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影响因子：
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作者：
Clements, KM;Price, JS;Mason, RM
通讯作者：
Mason, RM
DOI：
10.2741/martel
发表时间：
1999-10-15
期刊：
Frontiers in Bioscience
影响因子：
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作者：
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