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首页> 外文期刊>Cell and Tissue Research >Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice
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Effect of inhibiting MMP13 and ADAMTS5 by intra-articular injection of small interfering RNA in a surgically induced osteoarthritis model of mice

机译：抑制MMP13和Adamts5在手术诱导的小鼠骨关节炎模型中小干扰RNA的关节内注射

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Matrix metalloproteinase 13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) are thought to play critical roles in cartilage degradation at the early phase of osteoarthritis (OA). The aim of this study is to examine the effect of chemically modified Mmp13 or Adamts5 small interfering RNA (siRNA), alone or in combination, in a mouse OA model. OA pathology was surgically induced in 9-week-old male C57/BL6 mice (n = 64) via destabilization of the medial meniscus (DMM). We used chemically modified siRNA (Accell siRNAsA (R)) for Mmp13 and Adamts5, as well as a non-targeting control and evaluated their combined and individual effects after injection in the DMM model. The control group (n = 16) was injected with non-targeting siRNA and the normal group (n = 16) did not undergo any surgical induction or intra-articular injection. Histological assessment of the articular cartilage was conducted at 4 and 8 weeks post-DMM surgery to evaluate OA progression. Significant improvement in the histological score was observed at 8 weeks after DMM in all three siRNA-treated groups compared to the control siRNA-injected group. The score of the combined group was significantly lower than that of the Adamts5 siRNA-only group. No significant differences were noted between the Mmp13 siRNA-only group and the combined group. Combined intra-articular injection of Mmp13 and Adamts5 siRNA resulted in almost the same inhibitory effects as Mmp13 siRNA alone on cartilage degradation at the early phase of OA.
机译：基质金属蛋白酶13（MMP13）和具有血小板上蛋白基序5（ADAMTS5）的解毒素和金属蛋白酶被认为在骨关节炎早期阶段的软骨降解中发挥关键作用。本研究的目的是在小鼠OA模型中检查化学修饰的MMP13或AdamTS5小干扰RNA（siRNA），单独或组合的影响。通过内侧弯月面（DMM）的稳定化，在9周龄雄性C57 / BL6小鼠（n = 64）中诱导了OA病理学。我们使用化学修饰的siRNA（Accell SiRNA（R））用于MMP13和Adamts5，以及非靶向对照，并在DMM模型中注射后评估其组合和个体效果。对照组（n = 16）注射非靶向siRNA，并且正常组（n = 16）未进行任何手术诱导或内颈内注射。关节软骨的组织学评估在DMM手术后4和8周进行，以评估OA进展。与对照SiRNA注射的基团相比，在所有三个siRNA治疗组中，在DMM后8周观察到组织学评分的显着改善。合并组的得分显着低于Adamts5 siRNA的群体。在MMP13 siRNA组和组合组之间没有发现显着差异。关节内注射的MMP13和AdamTS5 siRNA导致几乎与单独的MMP13 siRNA在OA的早期阶段的软骨降解相同的抑制作用。

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