Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Department of Orthopedic Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Sci Rep. 2017 Feb 22;7:43205. doi: 10.1038/srep43205.
Pathophysiological events that modulate the progression of structural changes in osteoarthritis (OA) include the secretion of inflammatory molecules, such as proinflammatory cytokines. Interleukin-1beta (IL-1β) is the prototypical inflammatory cytokine that activates OA synovial cells to release cytokines and chemokines in support of the inflammatory response. The monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes in response to inflammation. We show in this study that IL-1β-induced MCP-1 expression and monocyte migration in OA synovial fibroblasts (OASFs) is effectively inhibited by soya-cerebroside, an extract of Cordyceps militaris. We found that soya-cerebroside up-regulated of microRNA (miR)-432 expression via inhibiting AMPK and AKT signaling pathways in OASFs. Soya-cerebroside also effectively decreased monocyte infiltration and prevented cartilage degradation in a rat inflammatory model. Our findings are the first to demonstrate that soya-cerebroside inhibits monocyte/macrophage infiltration into synoviocytes, attenuating synovial inflammation and preventing cartilage damage by reducing MCP-1 expression in vitro and in vivo. Taken together, we suggest a novel therapeutic strategy based on the use of soya-cerebroside for the management of OA.
调节骨关节炎 (OA) 结构变化进展的病理生理事件包括炎症分子的分泌,如促炎细胞因子。白细胞介素-1β (IL-1β) 是典型的炎症细胞因子,可激活 OA 滑膜细胞释放细胞因子和趋化因子,以支持炎症反应。单核细胞趋化蛋白-1 (MCP-1/CCL2) 是调节单核细胞迁移和浸润的关键趋化因子之一,以响应炎症。我们在这项研究中表明,IL-1β 诱导的 OA 滑膜成纤维细胞 (OASF) 中 MCP-1 的表达和单核细胞迁移被虫草素的提取物——大豆脑苷脂有效抑制。我们发现大豆脑苷脂通过抑制 OASF 中的 AMPK 和 AKT 信号通路而上调 microRNA (miR)-432 的表达。大豆脑苷脂还可有效减少单核细胞浸润并预防炎症模型中的软骨降解。我们的研究结果首次证明,大豆脑苷脂通过减少 MCP-1 的表达,在体外和体内抑制单核细胞/巨噬细胞浸润滑膜细胞,从而减轻滑膜炎症和防止软骨损伤,从而为 OA 的治疗提供了一种新的策略。