Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues
Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues
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细胞外 HMGB-1 激活肌腱细胞和组织中的炎症信号传导
DOI：
10.1177/2040622320956429
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发表时间：
2020-01
影响因子：
3.5
通讯作者：
Zhou Yiqin
中科院分区：
文献类型：
--
作者：
Zhang Chuanxin;Gu Xinfeng;Zhao Guangyi;Wang Wang;Shao Jiahua;Zhu Jun;Yuan Ting;Sun Jiuyi;Nie Daibang;Zhou Yiqin
背景：越来越多的证据表明，高迁移率族蛋白 1 (HMGB-1) 的分泌与肌腱病的发生具有功能相关性。然而，细胞外HMGB-1对肌腱细胞的潜在作用和机制尚不清楚。方法：我们用分离的大鼠跟腱细胞测试了外源 HMGB-1 对细胞生长、迁移和炎症信号反应的影响。此外，我们还研究了细胞外 HMGB-1 单独给药或与强化跑步机跑步 (ITR) 引起的机械超负荷联合给药时，在刺激肌腱组织炎症反应中的作用。结果：通过使用体外和体内模型，我们首次证明外源性 HMGB-1 剂量依赖性地诱导肌腱细胞和肌腱组织的炎症反应。细胞外 HMGB-1 促进 HMGB-1 从细胞核重新分布到细胞质，并激活经典核因子 kappa B (NF-κB) 信号和丝裂原激活蛋白激酶 (MAPK) 信号。短期施用 HMGB-1 可诱导大鼠跟腱组织细胞增多，并伴有免疫细胞浸润增强。对 HMGB-1 进行额外的 ITR 治疗会使这些反应恶化，而使用 HMGB-1 特异性抑制剂甘草甜素 (GL) 可以完全消除肌腱组织中的此类炎症效应。结论：总的来说，这些结果证实了 HMGB-1 在诱发肌腱病中发挥着关键作用。我们的研究结果提高了对肌腱病发展过程中分子和细胞机制的理解，并为肌腱病的潜在靶向治疗提供了重要信息。
Background: Increasing evidence indicates that secretion of high mobility group box 1 protein (HMGB-1) is functionally associated with tendinopathy development. However, the underlying effect and mechanism of extracellular HMGB-1 on tendon cells are unclear. Methods: We tested the effect of exogenous HMGB-1 on cell growth, migration, and inflammatory signaling responses with isolated rat Achilles tendon cells. Also, we studied the role of extracellular HMGB-1, when administrated alone or in combination with mechanical overloading induced by intensive treadmill running (ITR), in stimulating inflammatory effects in tendon tissues. Results: By using in vitro and in vivo models, we show for the first time that exogenous HMGB-1 dose-dependently induces inflammatory reactions in tendon cells and tendon tissue. Extracellular HMGB-1 promoted redistribution of HMGB-1 from the nucleus to the cytoplasm, and activated canonical nuclear factor kappa B (NF-κB) signaling and mitogen-activated protein kinase (MAPK) signaling. Short-term administration of HMGB-1 induced hyper-cellularity of rat Achilles tendon tissues, accompanied with enhanced immune cell infiltration. Additional ITR to HMGB-1 treatment worsens these responses, and application of HMGB-1 specific inhibitor glycyrrhizin (GL) completely abolishes such inflammatory effects in tendon tissues. Conclusion: Collectively, these results confirm that HMGB-1 plays key roles in the induction of tendinopathy. Our findings improve the understanding of the molecular and cellular mechanisms during tendinopathy development, and provide essential information for potential targeted treatments of tendinopathy.
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影响因子：
82.9
作者：
Bi, Yanming;Ehirchiou, Driss;Young, Marian F.
通讯作者：
Young, Marian F.
DOI：
10.1002/jor.24690
发表时间：
2020-04
期刊：
Journal of Orthopaedic Research®
影响因子：
--
作者：
Ying Zhang;Xiang-Hua Deng;Amir Lebaschi;Susumu Wada;C. Carballo;Brett Croen;L. Ying;S. Rodeo
通讯作者：
Ying Zhang;Xiang-Hua Deng;Amir Lebaschi;Susumu Wada;C. Carballo;Brett Croen;L. Ying;S. Rodeo
影响因子：
1.5
作者：
Federer, Andrew E.;Steele, John R.;Adams, Samuel B.
通讯作者：
Adams, Samuel B.
DOI：
10.1038/s41584-019-0364-x
发表时间：
2020-04
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Gracey E;Burssens A;Cambré I;Schett G;Lories R;McInnes IB;Asahara H;Elewaut D
通讯作者：
Elewaut D
影响因子：
7.5
作者：
Doganyigit, Zuleyha;Okan, Asli;Silici, Sibel
通讯作者：
Silici, Sibel