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Global Responses of Il-1β-Primed 3D Tendon Constructs to Treatment with Pulsed Electromagnetic Fields

机译:Il-1β为主的3D腱结构对脉冲电磁场​​处理的整体响应

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摘要

Tendinopathy is accompanied by a cascade of inflammatory events promoting tendon degeneration. Among various cytokines, interleukin-1β plays a central role in driving catabolic processes, ultimately resulting in the activation of matrix metalloproteinases and a diminished collagen synthesis, both of which promote tendon extracellular matrix degradation. Pulsed electromagnetic field (PEMF) therapy is often used for pain management, osteoarthritis, and delayed wound healing. In vitro PEMF treatment of tendon-derived cells was shown to modulate pro-inflammatory cytokines, potentially limiting their catabolic effects. However, our understanding of the underlying cellular and molecular mechanisms remains limited. We therefore investigated the transcriptome-wide responses of Il-1β-primed rat Achilles tendon cell-derived 3D tendon-like constructs to high-energy PEMF treatment. RNASeq analysis and gene ontology assignment revealed various biological processes to be affected by PEMF, including extracellular matrix remodeling and negative regulation of apoptosis. Further, we show that members of the cytoprotective Il-6/gp130 family and the Il-1β decoy receptor Il1r2 are positively regulated upon PEMF exposure. In conclusion, our results provide fundamental mechanistic insight into the cellular and molecular mode of action of PEMF on tendon cells and can help to optimize treatment protocols for the non-invasive therapy of tendinopathies.
机译:肌腱病伴随着一系列促进肌腱变性的炎症事件。在各种细胞因子中,白介素-1β在驱动分解代谢过程中起着核心作用,最终导致基质金属蛋白酶的活化和胶原蛋白合成的减少,两者均促进肌腱细胞外基质降解。脉冲电磁场​​(PEMF)治疗通常用于疼痛处理,骨关节炎和伤口愈合延迟。肌源性细胞的体外PEMF处理显示出可调节促炎性细胞因子,可能限制其分解代谢作用。但是,我们对潜在的细胞和分子机制的理解仍然有限。因此,我们研究了II-1β引发的大鼠跟腱细胞来源的3D肌腱样结构对高能PEMF治疗的转录组范围内的应答。 RNASeq分析和基因本体论研究揭示了PEMF影响各种生物学过程,包括细胞外基质重塑和细胞凋亡的负调控。此外,我们显示细胞保护性Il-6 / gp130家族成员和Il-1β诱饵受体Il1r2在PEMF暴露后受到正调控。总之,我们的结果提供了对PEMF在肌腱细胞上作用的细胞和分子模式的基本机制的了解,并有助于优化肌腱病的非侵入性治疗方案。

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