Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model.
Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model.
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DOI：
10.1302/2046-3758.56.bjr-2015-0001
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发表时间：
2016-06
影响因子：
4.6
通讯作者：
Cui YP
中科院分区：
文献类型：
--
作者：
Cheng NT;Guo A;Cui YP
最近的研究表明，全身注射雷帕霉素可以预防人类软骨细胞发生骨关节炎（OA）样变化，并减轻实验性 OA 的严重程度。然而，全身注射雷帕霉素会导致许多副作用。本研究的目的是确定关节内注射 Torin 1 对兔骨关节炎模型关节软骨退变的影响，并探讨 Torin 1 对实验性 OA 影响的机制。 Torin 1 是 mTOR 的特异性抑制剂，可诱导自噬，与雷帕霉素类似。将胶原酶（II 型）注射到 3 个月大的兔子的双膝中两次以诱导 OA，并结合两次关节内注射 Torin 1 (400 nM)。注射后八周，使用Mankin评分系统通过组织学评估关节软骨的退化。透射电镜观察软骨细胞变性和自噬体。通过定量RT-PCR (qPCR) 分析基质金属肽酶-13 (MMP-13) 和血管内皮生长因子(VEGF) 表达。通过Western blotting 检查Beclin-1 和轻链3 (LC3) 表达。关节内注射 Torin 1 显着减少诱导 OA 后关节软骨的退化。 Torin 1 处理的兔子软骨细胞中自噬体、Beclin-1 和 LC3 表达增加。注射胶原酶后八周，Torin 1 治疗还降低了 MMP-13 和 VEGF 的表达。我们的结果表明，关节内注射 Torin 1 可减少胶原酶诱导的 OA 中关节软骨的退化，至少部分是通过自噬激活，这提出了一种预防软骨退化和治疗 OA 的新治疗方法。引用这篇文章：N-T。程，A. 郭，Y-P。崔。关节内注射 Torin 1 可减少兔骨关节炎模型中关节软骨的退化。骨关节研究2016；5：218–224。 DOI：10.1302/2046-3758.56.BJR-2015-0001。
Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001.