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Cyclic Stretching Exacerbates Tendinitis by Enhancing NLRP3 Inflammasome Activity via F-Actin Depolymerization

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Abstract

Modern molecular techniques have highlighted the presence of inflammation throughout the spectrum of tendinopathy. Previous studies have suggested that excessive inflammation in the tendon is a major factor leading to poor clinical treatment. Furthermore, the NLRP3 inflammasome, as a new term, is closely associated with the pathogenesis of many diseases. In the present study, we examined whether the NLRP3 inflammasome contributes to the development of tendinitis and whether cyclic stretching plays a prominent role in inflammation in the tendon. In the present study, we showed that hydrogen peroxide (H2O2) remarkably enhances the expression and release of IL-1β, TNF-α, and IL-6. The maturation of IL-1β, induced by H2O2, depends on the activation of the NLRP3 inflammasome. Cyclic stretching enhances the maturation of IL-1β via promoting H2O2-induced NLRP3 inflammasome activation in tenocytes. Furthermore, we also found that the depolymerization of filamentous actin (F-actin) was required for cyclic stretching-enhanced NLRP3 inflammasome activation. The present study suggests that NLRP3 inflammasome plays an important regulatory role in the pathogenesis of tendinitis. Disruption of the cytoskeleton by cyclic stretching exerts a proinflammatory effect via further activating the NLRP3/IL-1β pathway and hence contributes to tendinitis. These results may provide theoretical support for a new treatment strategy for preventing excessive inflammation in the tendon.

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Acknowledgements

The present study was financially supported by grants from the Natural National Science Foundation of China (11532004, 31700810, and 11772073), the Exchange Program of the National Natural Science Foundation of China and Japan Society for the Promotion of Science (11511140092), the China Postdoctoral Science Foundation (2016M602657), and the Postdoctoral Research Program of Chongqing (Xm2016033).

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  1. Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Ministry of Education, Chongqing University, Chongqing, 400044, China

    Qiufang Chen, Bingyu Zhang, Zhe Chen, Qing Luo & Guanbin Song

  2. School of Life Science, Chongqing University, Chongqing, 400044, People’s Republic of China

    Jun Zhou

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  1. Qiufang Chen
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Chen, Q., Zhou, J., Zhang, B. et al. Cyclic Stretching Exacerbates Tendinitis by Enhancing NLRP3 Inflammasome Activity via F-Actin Depolymerization. Inflammation 41, 1731–1743 (2018). https://doi.org/10.1007/s10753-018-0816-5

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