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首页> 外文期刊>Journal of cellular physiology. >The P2X7 purinergic receptor in intervertebral disc degeneration
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The P2X7 purinergic receptor in intervertebral disc degeneration

机译：在椎间的P2X7受体purinergic椎间盘变性

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Abstract Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)‐1β expression in IVD specimens at different stages of disease progression, and during the in vitro dedifferentiation process of the primary cells derived thereof. We found that P2X7R, NLRP3, and IL‐1β expression was higher in the IVD samples at a more advanced stage of degeneration and in the expanded IVD cells in culture which partially recapitulated the in vivo degeneration process. In IVD cells, the P2X7R showed a striking nuclear localization, while NLRP3 was mainly cytoplasmic. Stimulation with the semiselective P2X7R agonist benzoyl ATP together with lipopolysaccharide treatment triggered P2X7R transfer to the cytoplasm and P2X7R/NLRP3 colocalization. Taken together, these findings support pathophysiological evidence that the degenerated disc is a highly inflamed microenvironment and highlight the P2X7R/NLRP3 axis as a suitable therapeutic target. The immunohistochemical analysis and the assessment of subcellular localization revealed a substantial expression of P2X7R also in normal disc tissue. This gives us the opportunity to contribute to the few studies performed in natively expressed human P2X7R so far, and to understand the possible physiological ATP‐mediated P2X7R homeostasis signaling. Therefore, collectively, our findings may offer a new perspective and pave the way for the exploration of a role of P2X7R‐mediated purinergic signaling in IVD metabolism that goes beyond its involvement in inflammation.
机译：抽象发展的机制椎间盘变性只)部分已知,因此实现有效的治疗非常困难。研究中,我们调查了P2X7 purinergic受体(P2X7R) NLRP3 inflammasome和白介素(IL)量1β在试管标本在不同的表达疾病进展的阶段,期间体外去分化的主要过程细胞。NLRP3和IL 1β表达更高的试管变性的样品在一个更高级的阶段和扩大试管培养细胞中部分重现了体内变性的过程。引人注目的核本地化,而NLRP3主要是胞质。semiselective P2X7R受体激动剂苯甲酰ATP结合在一起脂多糖治疗P2X7R触发转移到细胞质和P2X7R / NLRP3colocalization。病理生理的证据支持退化盘是一个高度发炎微环境和突出P2X7R / NLRP3轴是一个合适的治疗目标。免疫组织化学分析和评估的亚细胞定位显示大量表达P2X7R也正常椎间盘组织。为执行的一些研究本机表达人类P2X7R迄今为止,理解可能的生理ATP量P2X7R内稳态信号介导的。因此,总的来说,我们的研究结果可能会提供一个新的视角和铺平了道路探索P2X7R介导应承担的角色purinergic信号在试管的新陈代谢超出其参与炎症。

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