"Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration".

IF 2.6 3区医学 Q2 CLINICAL NEUROLOGY European Spine Journal Pub Date : 2024-11-14 DOI:10.1007/s00586-024-08550-w

Gowdaman Vasudevan, Karthik Ramachandran, Chitraa Tangavel, Sharon Miracle Nayagam, Chellappa Gopalakrishnan, Raveendran Muthurajan, K S Sri Vijay Anand, Shanmuganathan Rajasekaran

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Abstract

Purpose: The endocannabinoid system (ECS) has been well-established to play a crucial role in the regulation of several physiological processes as well as many inflammatory disease conditions. However, its role in intervertebral disc degeneration has been least explored. We aim to investigate the immunomodulatory role of endocannabinoids in regulating IVD health.

Methods: The study population included 20 healthy volunteers (controls) and 40 patients with disc degeneration (disease group) (20 Modic and 20 Non Modic). 16S metagenome sequencing of the V3-V4 region was performed for the DNA extracted from NP tissue samples of both control and disease groups. Sequencing was carried out using the Novaseq 6000 platform using 250 bp paired-end chemistry. A global metabolic profile was obtained using the uHPLC system coupled with Q Exactive Plus Hybrid Quadrupole-Orbitrap mass spectrometer.

Results: Our study revealed a higher prevalence of gram-negative bacteria, particularly opportunistic pathogens like Pseudomonas, in diseased discs (71-81%) compared to healthy controls (54%). Further investigation using metabolomics identified significant changes in the lipid profiles of diseased discs. We found that the signalling molecules of the ECS, 2-arachidonylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), were significantly lower in diseased discs compared to controls (Log2FC -2.62 for 2-AG and -3.15 for AEA). Conversely, pro-inflammatory metabolites like LTA4, HPETE, HETE, and Prostaglandin G2 were elevated in diseased discs, with a Log2 fold increase greater than 2.5.

Conclusion: The study reveals that the endocannabinoid metabolites (2-AG and AEA) of the ECS could be a significant molecule influencing susceptibility to infection and inflammation within the intervertebral discs, which could be a potential target for improving disc health.

Level of evidence: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

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"阐明内源性大麻素在椎间盘退化中的免疫调节作用"。

目的：内源性大麻素系统（ECS）在调节多种生理过程和多种炎症疾病中发挥着至关重要的作用，这一点已得到充分证实。然而，人们对其在椎间盘退变中的作用探索得最少。我们旨在研究内源性大麻素在调节椎间盘健康中的免疫调节作用：研究对象包括 20 名健康志愿者（对照组）和 40 名椎间盘退变患者（疾病组）（20 名 Modic 和 20 名 Non Modic）。从对照组和疾病组的 NP 组织样本中提取的 DNA 进行了 V3-V4 区域的 16S 元基因组测序。测序采用 Novaseq 6000 平台，使用 250 bp 成对末端化学方法进行。使用 uHPLC 系统和 Q Exactive Plus 混合型四极杆-轨道阱质谱仪获得了全球代谢图谱：结果：我们的研究发现，与健康对照组（54%）相比，患病椎间盘中的革兰氏阴性菌，尤其是假单胞菌等机会致病菌的感染率更高（71%-81%）。利用代谢组学进行的进一步研究发现，患病椎间盘的脂质特征发生了显著变化。我们发现，与对照组相比，病变椎间盘中的 ECS 信号分子--2-丙烯酰甘油（2-AG）和 N-丙烯酰乙醇胺（AEA）含量明显降低（2-AG 的 Log2FC 为-2.62，AEA 为-3.15）。相反，病变椎间盘中的促炎代谢物如 LTA4、HPETE、HETE 和前列腺素 G2 则升高，Log2 倍增倍数大于 2.5：研究揭示，ECS 的内源性大麻素代谢物（2-AG 和 AEA）可能是影响椎间盘感染和炎症易感性的重要分子，这可能是改善椎间盘健康的潜在目标：诊断性：具有一致参考标准和盲法的单项横断面研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Spine Journal 医学-临床神经学

CiteScore

4.80

自引率

10.70%

发文量

373

审稿时长

2-4 weeks

期刊介绍： "European Spine Journal" is a publication founded in response to the increasing trend toward specialization in spinal surgery and spinal pathology in general. The Journal is devoted to all spine related disciplines, including functional and surgical anatomy of the spine, biomechanics and pathophysiology, diagnostic procedures, and neurology, surgery and outcomes. The aim of "European Spine Journal" is to support the further development of highly innovative spine treatments including but not restricted to surgery and to provide an integrated and balanced view of diagnostic, research and treatment procedures as well as outcomes that will enhance effective collaboration among specialists worldwide. The “European Spine Journal” also participates in education by means of videos, interactive meetings and the endorsement of educative efforts. Official publication of EUROSPINE, The Spine Society of Europe