Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways.
Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways.
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DOI：
10.1186/s13075-021-02512-z
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发表时间：
2021-05-14
影响因子：
4.9
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Lu J;Zhang H;Pan J;Hu Z;Liu L;Liu Y;Yu X;Bai X;Cai D;Zhang H
目的：探讨白玉兰主要成分白玉兰蛋白在骨关节炎（OA）发展过程中软骨和滑膜巨噬细胞重编程和串扰中的作用及其调控机制。将10周龄雄性C57BL/6小鼠随机分为载药组、胶原酶诱导的OA （CIOA）组和CIOA联合关节内蛋白治疗组。关节软骨退变采用国际骨关节炎研究协会（OARSI）评分进行评估。免疫染色和western blot检测相关蛋白。用LPS或IL-4处理Raw264.7细胞，研究极化巨噬细胞的作用。用IL-1β处理ADTC5细胞，收集条件培养基，观察软骨细胞和巨噬细胞之间的串扰。Fargesin减轻了关节软骨退变和滑膜炎，导致国际骨关节炎研究学会（OARSI）和滑膜炎评分显著降低。特别是，与对照组相比，fagesin处理的CIOA小鼠滑膜巨噬细胞M2极化明显增加，M1极化明显减少。同时血清中IL-6、IL-1β下调，IL-10上调。经蛋白蛋白酶处理的M1巨噬细胞条件培养基（CM）降低了OA软骨细胞中基质金属蛋白酶-13、RUNX2和X型胶原的表达，并增加了Col2a1和SOX9的表达，但单独使用蛋白蛋白酶不影响软骨细胞的分解代谢过程。此外，fargesin通过抑制p38/ERK MAPK和p65/NF-κB信号通路发挥保护作用。本研究表明，fargesin通过下调p38/ERK MAPK和p65/NF-κB信号，将巨噬细胞的极化表型从M1亚型转换为M2亚型，部分阻止软骨退变。针对巨噬细胞重编程或阻断巨噬细胞与软骨细胞之间的串扰可能是早期OA的有效预防策略。
To investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development. Ten-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages. Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling. This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.
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影响因子：
27.4
作者：
Atukorala I;Kwoh CK;Guermazi A;Roemer FW;Boudreau RM;Hannon MJ;Hunter DJ
通讯作者：
Hunter DJ
影响因子：
4.6
作者：
Fu, Ting;Chai, Bowen;Ye, Xiyun
通讯作者：
Ye, Xiyun
五味子 B 通过抑制 NF-κB 和 MAPK 信号通路改善软骨细胞炎症和骨关节炎。
DOI：
10.2147/dddt.s162014
发表时间：
2018
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Ran J;Ma C;Xu K;Xu L;He Y;Moqbel SAA;Hu P;Jiang L;Chen W;Bao J;Xiong Y;Wu L
通讯作者：
Wu L
DOI：
10.1038/nrrheum.2016.136
发表时间：
2016-10
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Robinson WH;Lepus CM;Wang Q;Raghu H;Mao R;Lindstrom TM;Sokolove J
通讯作者：
Sokolove J
全氟辛烷磺酸通过线粒体依赖性和 NF-κB/TNF-α 介导的途径诱导氧化性肝损伤
影响因子：
8.8
作者：
Han, Rui;Hu, Mingxian;Ding, Wenjun
通讯作者：
Ding, Wenjun