Zhang Chuanxin, Gu Xinfeng, Zhao Guangyi, Wang Wang, Shao Jiahua, Zhu Jun, Yuan Ting, Sun Jiuyi, Nie Daibang, Zhou Yiqin
Department of Joint Surgery and Sports Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Joint Surgery and Sports Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China Department of Bone and Joint, Shuguang Hospital Affiliated to Shanghai University of Tradition Chinese Medicine, Shanghai, China.
Ther Adv Chronic Dis. 2020 Sep 11;11:2040622320956429. doi: 10.1177/2040622320956429. eCollection 2020.
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.
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.
By using and 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.
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.
越来越多的证据表明，高迁移率族蛋白盒1（HMGB - 1）的分泌与肌腱病的发展在功能上相关。然而，细胞外HMGB - 1对肌腱细胞的潜在作用和机制尚不清楚。
我们用分离的大鼠跟腱细胞测试了外源性HMGB - 1对细胞生长、迁移和炎症信号反应的影响。此外，我们研究了单独给予细胞外HMGB - 1或与高强度跑步机跑步（ITR）诱导的机械过载联合使用时，其在刺激肌腱组织炎症反应中的作用。
通过使用[具体模型1]和[具体模型2]模型，我们首次表明外源性HMGB - 1剂量依赖性地诱导肌腱细胞和肌腱组织中的炎症反应。细胞外HMGB - 1促进了HMGB - 1从细胞核向细胞质的重新分布，并激活了经典的核因子κB（NF - κB）信号和丝裂原活化蛋白激酶（MAPK）信号。短期给予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。在HMGB - 1治疗基础上额外进行ITR会使这些反应恶化，而应用HMGB - 1特异性抑制剂甘草甜素（GL）可完全消除肌腱组织中的此类炎症效应。
总体而言，这些结果证实HMGB - 1在肌腱病的诱导中起关键作用。我们的研究结果增进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。
