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Laquinimod Mitigated IL-1β-Induced Impairment of the Cartilage Extracellular Matrix in Human ATDC5 Chondrocytes.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-03-19 , DOI: 10.1021/acs.chemrestox.9b00482 Peng Xie 1 , Feng Dan 1 , Guoyong Yu 1 , Wenhui Ruan 1 , Hong Yu 1
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-03-19 , DOI: 10.1021/acs.chemrestox.9b00482 Peng Xie 1 , Feng Dan 1 , Guoyong Yu 1 , Wenhui Ruan 1 , Hong Yu 1
Affiliation
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To date, a safe and reliable treatment of osteoarthritis (OA) has not yet been announced. Inflammatory response and degradation of the articular extracellular matrix (ECM) induced by IL-1β are important pathological characteristics of OA. Laquinimod is a quinoline-3-carboxamide and a novel oral immunomodulatory compound in clinical use. However, whether laquinimod has a beneficial effect in OA is not known. In our research, we found that laquinimod could ameliorate IL-1β-induced generation of ROS and improve mitochondrial function by increasing mitochondrial membrane potential (ΔΨm). Furthermore, treatment with laquinimod suppressed IL-1β-induced production of TNF-α and IL-6. Notably, laquinimod prevented the degradation of type II collagen by inhibiting MMP-3 and MMP-13. Meanwhile, the presence of laquinimod attenuated the reduction in aggrecan by mediating ADAMTS-4 and ADAMTS-5. Mechanistically, laquinimod ameliorated IL-1β-induced inflammation and degeneration of ECM by suppressing the activation of NF-κB. Taken together, our findings reveal that laquinimod possesses a beneficial effect against IL-1β insults in human chondrocytes, implying an important role of laquinimod in OA.
中文翻译：
拉喹莫德缓解了人ATDC5软骨细胞中IL-1β诱导的软骨细胞外基质的损伤。
迄今为止，尚未宣布安全可靠的骨关节炎（OA）治疗方法。IL-1β引起的炎症反应和关节细胞外基质（ECM）降解是OA的重要病理特征。拉喹莫德是一种喹啉-3-羧酰胺，在临床上是一种新型的口服免疫调节化合物。然而，拉喹莫德在OA中是否具有有益作用尚不清楚。在我们的研究中，我们发现拉喹莫德可以通过增加线粒体膜电位（ΔΨm）来改善IL-1β诱导的ROS生成并改善线粒体功能。此外，用拉喹莫德治疗抑制了IL-1β诱导的TNF-α和IL-6的产生。值得注意的是，拉喹莫德通过抑制MMP-3和MMP-13阻止了II型胶原的降解。与此同时，拉喹莫德的存在通过介导ADAMTS-4和ADAMTS-5减弱了聚集蛋白聚糖的减少。从机理上讲，拉喹莫德通过抑制NF-κB的活化改善了IL-1β引起的炎症和ECM变性。综上所述，我们的发现表明拉喹莫德对人软骨细胞中的IL-1β损伤具有有益的作用，这暗示了拉喹莫德在OA中的重要作用。
更新日期：2020-04-23
中文翻译：
拉喹莫德缓解了人ATDC5软骨细胞中IL-1β诱导的软骨细胞外基质的损伤。
迄今为止，尚未宣布安全可靠的骨关节炎（OA）治疗方法。IL-1β引起的炎症反应和关节细胞外基质（ECM）降解是OA的重要病理特征。拉喹莫德是一种喹啉-3-羧酰胺，在临床上是一种新型的口服免疫调节化合物。然而，拉喹莫德在OA中是否具有有益作用尚不清楚。在我们的研究中，我们发现拉喹莫德可以通过增加线粒体膜电位（ΔΨm）来改善IL-1β诱导的ROS生成并改善线粒体功能。此外，用拉喹莫德治疗抑制了IL-1β诱导的TNF-α和IL-6的产生。值得注意的是，拉喹莫德通过抑制MMP-3和MMP-13阻止了II型胶原的降解。与此同时，拉喹莫德的存在通过介导ADAMTS-4和ADAMTS-5减弱了聚集蛋白聚糖的减少。从机理上讲，拉喹莫德通过抑制NF-κB的活化改善了IL-1β引起的炎症和ECM变性。综上所述，我们的发现表明拉喹莫德对人软骨细胞中的IL-1β损伤具有有益的作用，这暗示了拉喹莫德在OA中的重要作用。
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