Differentiated embryonic chondrocyte expressed gene-1 is a central signaling component in the development of collagen-induced rheumatoid arthritis.
Differentiated embryonic chondrocyte expressed gene-1 is a central signaling component in the development of collagen-induced rheumatoid arthritis.
复制标题
分化的胚胎软骨细胞表达的gene-1是胶原诱导的类风湿性关节炎发展中的核心信号成分。
DOI：
10.1016/j.jbc.2023.102982
复制
发表时间：
2023-03
影响因子：
4.8
通讯作者：
Yang, Jian
中科院分区：
文献类型：
--
作者：
Wu, Yichen;Wang, Haobin;Huo, Ying;Yan, Bingfang;Honda, Hiroaki;Liu, Wei;Yang, Jian
风湿性关节炎（RA）是最常见的自身免疫性疾病之一，影响近1%的人口。分化的胚胎软骨细胞表达基因1（DEC 1）与骨生成和破骨细胞生成有关。RA的特征是炎症性增生，已知DEC 1支持炎症反应并参与抗凋亡和细胞侵袭。在这里，我们的目标是测试DEC 1增强胶原诱导性关节炎（CIA）诱导的RA发展的假设，CIA是开发RA动物模型的公认方案。对DEC 1 +/+和DEC 1-/-小鼠进行CIA方案，并监测RA状况的发展。我们发现CIA强烈诱导RA表型（例如，滑膜增生）并显著增加促炎细胞因子如TNF-α的表达。然而，这些变化在DEC 1 +/+小鼠中检测到，而在DEC 1 −/−小鼠中未检测到。有趣的是，这些细胞因子强烈诱导DEC 1，并且DEC 1作为促炎细胞因子的诱导物和被促炎细胞因子诱导的这种双重作用构成了DEC 1炎症放大回路。在人MH 7A细胞中DEC 1的敲低强烈降低细胞迁移和侵袭以及与RA表型相关的基因的表达。DEC 1介导的体外迁移和侵袭与体内滑膜增生的结合机制建立了DEC 1如何参与RA表型发展的细胞基础。除了炎症信号，DEC 1在功能上与PI 3 KCA（p110α）/Akt/GSK 3 β、Wnt/β-catenin和NFATc 1相互作用。这种参与多个信号通路表明，DEC 1在发展RA中发挥协调和整体作用，RA是最常见的自身免疫性疾病之一。
Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and affects almost 1% of the population. Differentiated embryo-chondrocyte expressed gene-1 (DEC1) has been associated with both osteogenesis and osteoclastogenesis. RA condition is marked by inflammatory hyperplasia, and DEC1 is known to support inflammatory reactions and implicated in antiapoptosis and cell invasion. Here, our goal was to test the hypothesis that DEC1 enhances RA development induced by collagen-induced arthritis (CIA), a well-recognized protocol for developing RA animal models. DEC1+/+ and DEC1−/− mice were subjected to CIA protocol, and the development of RA condition was monitored. We found that CIA robustly induced RA phenotypes (e.g., synovial hyperplasia) and greatly increased the expression of proinflammatory cytokines such as TNF-α. However, these changes were detected in DEC1+/+ but not DEC1−/− mice. Interestingly, these very cytokines strongly induced DEC1, and such a dual role of DEC1, as an inducer for and being induced by proinflammatory cytokines, constitutes a DEC1-amplifying circuit for inflammation. Knockdown of DEC1 in human MH7A cells strongly decreased cell migration and invasion as well as the expression of genes related to RA phenotypes. The combination of DEC1-directed migration and invasion in vitro with synovial hyperplasia in vivo mechanistically establishes cellular bases on how DEC1 is involved in the development of RA phenotypes. In addition to inflammatory signaling, DEC1 functionally interacted with PI3KCA(p110α)/Akt/GSK3β, Wnt/β-catenin, and NFATc1. Such engagement in multiple signaling pathways suggests that DEC1 plays coordinated and integral roles in developing RA, one of the most common autoimmune diseases.
登录
查看更多内容
影响因子：
7.3
作者：
Achudhan D;Liu SC;Lin YY;Huang CC;Tsai CH;Ko CY;Chiang IP;Kuo YH;Tang CH
通讯作者：
Tang CH
淫羊藿苷可防止糖皮质激素诱导的骨质疏松症，增加骨增强剂 DEC1 的表达并调节 PI3K/Akt/GSK3β/β-连环蛋白整合信号通路。
影响因子：
5.8
作者：
Hu J;Mao Z;He S;Zhan Y;Ning R;Liu W;Yan B;Yang J
通讯作者：
Yang J
DEC1 缺乏通过增强 DKK1 活性和减弱 PI3KCA/Akt/GSK3β 信号传导导致加速骨质减少。
DOI：
10.1016/j.metabol.2021.154730
发表时间：
2021-05
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
He S;Guan Y;Wu Y;Zhu L;Yan B;Honda H;Yang J;Liu W
通讯作者：
Liu W
影响因子：
2.7
作者：
Lou, Lixia;Zhou, Jingwei;Chai, Limin
通讯作者：
Chai, Limin
影响因子：
2.7
作者：
Li, Shuai;Peng, Dan;Liu, Cong-Wei
通讯作者：
Liu, Cong-Wei