Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou 325000, Zhejiang Provinece, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China; The Second School of Medicine, WenZhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
Int Immunopharmacol. 2020 Jul;84:106511. doi: 10.1016/j.intimp.2020.106511. Epub 2020 May 1.
Osteoarthritis (OA) is a long-term, chronic, progressive joint condition caused by a pathology characterized by the deterioration of joint cartilage and proliferation of subchondral bone. Myricitrin (Myr) is a flavonoid compound extracted from myrica rubra with potent anti-inflammatory properties, as demonstrated in various studies. However, the mechanisms by which Myr plays a protective role in OA are not completely understood. In this study, the anti-inflammatory properties and potential mechanisms of Myr on mouse chondrocytes treated with interleukin (IL) -1beta (β) were explored in vitro and the role of Myr in a mouse model of OA in vivo. The production of pro-inflammatory factors, such as IL-6, tumor necrosis factor alpha (TNF-α), prostaglandin E2 (PGE2) and nitric oxide (NO) were assessed by enzyme linked immunosorbent assay (ELISA) and the Griess reaction. Protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Collagen-II, matrix metalloproteinase(MMP)-13, MMP-3, thrombospondin motifs 5(ADAMTS5), inhibitor ofnuclear factor kappa-B (IκB), p-IκB, p65, p-p65, c-jun-terminal kinase (JNK), p-JNK, extracellular regulated protein kinases (ERK), p-ERK, p38 and p-p38 were quantified using Western blot analysis. In the present study, we found that Myr inhibited IL-1β-induced production of NO and PGE2, expression of MMP-13, MMP-3 and ADAMTS5 and degradation of collagen-II in mouse chondrocytes. Mechanistically, Myr inhibited the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) treated with IL-1β in mouse chondrocytes. In vivo, Myr decreased OA Research Society International (OARSI) scores in a surgically-induced mouse model of OA. These data suggest that Myr could be developed as a potential therapyfor OA.
骨关节炎（OA）是一种长期、慢性、进行性的关节疾病，由关节软骨恶化和软骨下骨增生为特征的病理学引起。杨梅素（Myr）是一种从杨梅中提取的类黄酮化合物，具有很强的抗炎特性，这在各种研究中得到了证实。然而，Myr 在 OA 中发挥保护作用的机制尚不完全清楚。在这项研究中，我们在体外研究了 Myr 对白细胞介素（IL）-1β（β）处理的小鼠软骨细胞的抗炎特性及其潜在机制，并在体内研究了 Myr 在 OA 小鼠模型中的作用。通过酶联免疫吸附试验（ELISA）和格里斯反应评估促炎因子如白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、前列腺素 E2（PGE2）和一氧化氮（NO）的产生。诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、胶原-II、基质金属蛋白酶（MMP）-13、MMP-3、血小板反应蛋白基序 5（ADAMTS5）、核因子κB 抑制剂（IκB）、p-IκB、p65、p-p65、c-jun 末端激酶（JNK）、p-JNK、细胞外调节蛋白激酶（ERK）、p-ERK、p38 和 p-p38 的蛋白表达水平通过 Western blot 分析进行量化。在本研究中，我们发现 Myr 抑制了 IL-1β诱导的 NO 和 PGE2 的产生、MMP-13、MMP-3 和 ADAMTS5 的表达以及胶原-II 的降解在小鼠软骨细胞中。在机制上，Myr 抑制了 MAPK 和核因子 kappa-B（NF-κB）在 IL-1β处理的小鼠软骨细胞中的激活。在体内，Myr 降低了手术诱导的 OA 研究协会国际（OARSI）评分在 OA 小鼠模型中。这些数据表明，Myr 可开发为 OA 的潜在治疗方法。
