Vasudevan Gowdaman, Ramachandran Karthik, Tangavel Chitraa, Nayagam Sharon Miracle, Gopalakrishnan Chellappa, Muthurajan Raveendran, Sri Vijay Anand K S, Rajasekaran Shanmuganathan
Ganga Research Centre, SF No.442, NGGO Colony Post, Vattamalaipalayam, Coimbatore, TamilNadu, 641022, India.
Department of Spine Surgery, Ganga Hospital, 313, Mettupalayam Road, Coimbatore, India.
Eur Spine J. 2025 Jan;34(1):308-315. doi: 10.1007/s00586-024-08550-w. Epub 2024 Nov 14.
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.
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.
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.
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.
Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.
内源性大麻素系统（ECS）在多种生理过程以及许多炎症性疾病状态的调节中发挥关键作用已得到充分证实。然而，其在椎间盘退变中的作用研究最少。我们旨在研究内源性大麻素在调节椎间盘健康方面的免疫调节作用。
研究人群包括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型和20名非Modic型）。对从对照组和疾病组的髓核组织样本中提取的DNA进行V3-V4区域的16S宏基因组测序。使用Novaseq 6000平台，采用250 bp双端化学法进行测序。使用超高效液相色谱系统与Q Exactive Plus混合四极杆-轨道阱质谱仪获得全局代谢谱。
我们的研究表明，与健康对照组（54%）相比，患病椎间盘中革兰氏阴性菌，特别是如假单胞菌等机会性病原体的患病率更高（71%-81%）。使用代谢组学的进一步研究确定了患病椎间盘脂质谱的显著变化。我们发现，与对照组相比，患病椎间盘中ECS的信号分子2-花生四烯酸甘油酯（2-AG）和N-花生四烯酰乙醇胺（AEA）显著降低（2-AG的Log2FC为-2.62，AEA为-3.15）。相反，患病椎间盘中促炎代谢物如白三烯A4、氢过氧化二十碳四烯酸、羟化二十碳四烯酸和前列腺素G2升高，Log2倍增加大于2.5。
该研究表明，ECS的内源性大麻素代谢物（2-AG和AEA）可能是影响椎间盘内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靶点。
诊断性：采用一致应用的参考标准和盲法的个体横断面研究。
