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Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues.

ABSTRACT: 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-?B) 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.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7488923 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues.

Zhang Chuanxin C Gu Xinfeng X Zhao Guangyi G Wang Wang W Shao Jiahua J Zhu Jun J Yuan Ting T Sun Jiuyi J Nie Daibang D Zhou Yiqin Y

Therapeutic advances in chronic disease 20200911

<h4>Background</h4>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.<h4>Methods</h4>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 alo ...[more]

PMID: 32963751

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Project description:BackgroundTendon injuries are one of the most common musculoskeletal conditions in active patients. Platelet-rich plasma (PRP) has shown some promise in the treatment of tendon disorders, but little is known as to the mechanisms by which PRP can improve tendon regeneration. PRP contains numerous different growth factors and cytokines that activate various cellular signaling cascades, but it has been difficult to determine precisely which signaling pathways and cellular responses are activated after PRP treatment. Additionally, macrophages play an important role in modulating tendon regeneration, but the influence of PRP on determining whether macrophages assume a proinflammatory or anti-inflammatory phenotype remains unknown.PurposeTo use genome-wide expression profiling, bioinformatics, and protein analysis to determine the cellular pathways activated in fibroblasts treated with PRP. The effect of PRP on macrophage polarization was also evaluated.Study designControlled laboratory study.MethodsTendon fibroblasts or macrophages from rats were cultured and treated with either platelet-poor plasma (PPP) or PRP. RNA or protein was isolated from cells and analyzed using microarrays, quantitative polymerase chain reaction, immunoblotting, or bioinformatics techniques.ResultsPathway analysis determined that the most highly induced signaling pathways in PRP-treated tendon fibroblasts were TNFα and NFκB pathways. PRP also downregulated the expression of extracellular matrix genes and induced the expression of autophagy-related genes and reactive oxygen species (ROS) genes and protein markers in tendon fibroblasts. PRP failed to have a major effect on markers of macrophage polarization.ConclusionPRP induces an inflammatory response in tendon fibroblasts, which leads to the formation of ROS and the activation of oxidative stress pathways. PRP does not appear to significantly modulate macrophage polarization.Clinical relevancePRP might act by inducing a transient inflammatory event, which could then trigger a tissue regeneration response.

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Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues.

Publications

Extracellular HMGB-1 activates inflammatory signaling in tendon cells and tissues.

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