Gowdaman Vasudevan, Karthik Ramachandran, Chitraa Tangavel, Sharon Miracle Nayagam, Chellappa Gopalakrishnan, Raveendran Muthurajan, K S Sri Vijay Anand, Shanmuganathan Rajasekaran
{"title":"\"阐明内源性大麻素在椎间盘退化中的免疫调节作用\"。","authors":"Gowdaman Vasudevan, Karthik Ramachandran, Chitraa Tangavel, Sharon Miracle Nayagam, Chellappa Gopalakrishnan, Raveendran Muthurajan, K S Sri Vijay Anand, Shanmuganathan Rajasekaran","doi":"10.1007/s00586-024-08550-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Level of evidence: </strong>Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.</p>","PeriodicalId":12323,"journal":{"name":"European Spine Journal","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"\\\"Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration\\\".\",\"authors\":\"Gowdaman Vasudevan, Karthik Ramachandran, Chitraa Tangavel, Sharon Miracle Nayagam, Chellappa Gopalakrishnan, Raveendran Muthurajan, K S Sri Vijay Anand, Shanmuganathan Rajasekaran\",\"doi\":\"10.1007/s00586-024-08550-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Level of evidence: </strong>Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.</p>\",\"PeriodicalId\":12323,\"journal\":{\"name\":\"European Spine Journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-11-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Spine Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00586-024-08550-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Spine Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00586-024-08550-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
"Elucidating the immunomodulatory role of endocannabinoids in intervertebral disc degeneration".
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.
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
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