RAGE-dependent NF-kB inflammation processes in the capsule of frozen shoulders
RAGE-dependent NF-kB inflammation processes in the capsule of frozen shoulders
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DOI：
10.1016/j.jse.2020.01.076
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发表时间：
2020-09-01
影响因子：
3
通讯作者：
Itoi, Eiji
中科院分区：
文献类型：
--
作者：
Yano, Toshihisa;Hagiwara, Yoshihiro;Itoi, Eiji
背景：冻结肩（FS）的病因仍然不确定。晚期糖基化终产物（AGEs）引起胶原的交联和稳定，并在FS中增加。本研究的目的是阐明FS的发病机制，通过评估受体的AGE（AGE）依赖pathways.Methods：组织标本的喙肱韧带（CHL）和前下盂肱韧带（IGHL）收集33例FS，严重僵硬，和25肩袖撕裂（RCT）作为对照。采用实时定量聚合酶链反应评价TNF α、高迁移率族蛋白1（HMGB 1）、Toll样受体2（TLR 2）、TLR 4、核因子-κ B（NF-kB）和细胞因子的基因表达水平。还评价了羧甲基赖氨酸（CML）、戊糖甙和甘草酸的免疫反应性。结果：与RCT组相比，FS组CHLs和IGHLs中HMGB 1、TLR 2、TLR 4和NF-kB的基因表达水平均显著增高。FS组CHLs和IGHL中CML和CML的免疫反应性均强于RCT组。FS组CHLs和IGHL中的Pentosidine免疫染色较弱。结论：AGEs和HMGB 1可能通过与NF-kB信号通路结合，激活NF-kB信号通路，在FS的发病中发挥重要作用。抑制这些途径可能是FS的一种治疗选择。证据等级：基础科学研究;分子和细胞生物学（C）2020年肩肘外科董事会杂志。All rights reserved.
Background: The etiology of frozen shoulder (FS) remains uncertain. Advanced glycation end-products (AGEs) cause the cross-linking and stabilization of collagen and are increased in FS. The purpose of this study was to elucidate the pathogenesis of FS by evaluating the receptor of AGE (RAGE)-dependent pathways.Methods: Tissue samples of the coracohumeral ligament (CHL) and anterior inferior glenohumeral ligament (IGHL) were collected from 33 patients with FS, with severe stiffness, and 25 with rotator cuff tears (RCTs) as controls. Gene expression levels of RAGE, high-mobility group box 1 (HMGB1), Toll-like receptor 2 (TLR2), TLR4, nuclear factor-kappa B (NF-kB), and cytokines were evaluated using a quantitative real-time polymerase chain reaction. The immunoreactivities of carboxymethyllysine (CML), pentosidine, and RAGE were also evaluated. CML and pentosidine were further evaluated using high-performance liquid chromatography.Results: Gene expression levels of RAGE, HMGB1, TLR2, TLR4, and NF-kB were significantly greater in the CHLs and IGHLs from the FS group than in those from the RCT group. Immunoreactivities of RAGE and CML were stronger in the CHLs and IGHLs from the FS group than in those from the RCT group. Pentosidine was weakly immunostained in the CHLs and IGHLs from the FS group. CML using high-performance liquid chromatography was significantly greater in the CHLs and IGHLs from the FS group than in those from the RCT group.Conclusions: AGEs and HMGB1 might play important roles in the pathogenesis of FS by binding to RAGE and activating NF-kB signaling pathways. Suppression of these pathways could be a treatment option for FS. Level of evidence: Basic Science Study; Molecular and Cell Biology (C) 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.