Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC

Lie, Marie Udnesseter; Pedersen, Linda M.; Heuch, Ingrid; Winsvold, Bendik Slagsvold; Gjerstad, Johannes; Hasvik, Eivind; Nygaard, Øystein P.; Grotle, Margreth; Matre, Dagfinn; Zwart, John‐Anker; Nilsen, Kristian Bernhard

doi:10.3389/fgene.2021.757632

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…[ 5 , 6 , 7 ] Recently, the genome‐wide association studies (GWAS) have identified accumulated genetic loci. [ 8 , 9 , 10 , 11 ] A large‐scale GWAS study of over 500 000 individuals identified a common underlying genetic component between disc pathology and low back pain, identifying three BP‐associated loci. [ 8 ] Another large‐scale genome‐wide association study meta‐analysis identified 41 variants at 33 motifs associated with back pain.…”

Section: Introductionmentioning

confidence: 99%

Insight into the Causal Relationship between Gut Microbiota and Back Pain: A Two Sample Bidirectional Mendelian Randomization Study

Hui,

Chen,

et al. 2023

Advanced Genetics

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Observational studies have shown that alterations in gut microbiota composition are associated with low back pain. However, it remains unclear whether the association is causal. To reveal the causal association between gut microbiota and low back pain, a two‐sample bidirectional Mendelian randomization (MR) analysis is performed. The inverse variance weighted regression (IVW) is performed as the principal MR analysis. MR‐Egger and Weighted Median is further conducted as complementary analysis to validate the robustness of the results. Finally, a reverse MR analysis is performed to evaluate the possibility of reverse causation. The inverse variance weighted (IVW) method suggests that Peptostreptococcaceae (odds ratio [OR] 1.056, 95% confidence interval [CI] [1.015–1.098], PIVW = 0.010), and Lactobacillaceae (OR 1.070, 95% CI [1.026–1.115], PIVW = 0.003) are positively associated with back pain. The Ruminococcaceae (OR 0.923, 95% CI [0.849–0.997], PIVW = 0.033), Butyricicoccus (OR 0.920, 95% CI [0.868 ‐ 0.972], PIVW = 0.002), and Lachnospiraceae (OR 0.948, 95% CI [0.903–0.994], PIVW = 0.022) are negatively associated with back pain. In this study, underlying causal relationships are identified among gut microbiota and low back pain. Notably, further research is needed on the biological mechanisms by which gut microbiota influences low back pain.

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Section: Introductionmentioning

confidence: 99%

Insight into the Causal Relationship between Gut Microbiota and Back Pain: A Two Sample Bidirectional Mendelian Randomization Study

Hui,

Chen,

et al. 2023

Advanced Genetics

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“…In addition to the three above mentioned loci, a follow up study by Freidin et al also found that mutations in SPOCK2 and CHST3 potentially contribute to disc generation and general back pain in a study of 509,000 European individuals ( Freidin et al, 2019 ). However, there is debate as to whether the SOX5 , CCDC26/GSDMC , and DCC loci are associated with back pain based on another study of Caucasian individuals in Norway ( Lie et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods

Hickman

Kumar

Peck

2022

Front. Cell Dev. Biol.

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The intervertebral disc (IVD) is the fibrocartilaginous joint located between each vertebral body that confers flexibility and weight bearing capabilities to the spine. The IVD plays an important role in absorbing shock and stress applied to the spine, which helps to protect not only the vertebral bones, but also the brain and the rest of the central nervous system. Degeneration of the IVD is correlated with back pain, which can be debilitating and severely affects quality of life. Indeed, back pain results in substantial socioeconomic losses and healthcare costs globally each year, with about 85% of the world population experiencing back pain at some point in their lifetimes. Currently, therapeutic strategies for treating IVD degeneration are limited, and as such, there is great interest in advancing treatments for back pain. Ideally, treatments for back pain would restore native structure and thereby function to the degenerated IVD. However, the complex developmental origin and tissue composition of the IVD along with the avascular nature of the mature disc makes regeneration of the IVD a uniquely challenging task. Investigators across the field of IVD research have been working to elucidate the mechanisms behind the formation of this multifaceted structure, which may identify new therapeutic targets and inform development of novel regenerative strategies. This review summarizes current knowledge base on IVD development, degeneration, and regenerative strategies taken from traditional genetic approaches and omics studies and discusses the future landscape of investigations in IVD research and advancement of clinical therapies.

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Pyroptosis in health and disease

Imre

2024

American Journal of Physiology-Cell Physiology

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The field of cell death has witnessed significant advancements since the initial discovery of apoptosis in the 1970s. This review delves into the intricacies of pyroptosis, a more recently identified form of regulated, lytic cell death, and explores the roles of pyroptotic effector molecules, with a strong emphasis on their mechanisms and relevance in various diseases. Pyroptosis, characterized by its proinflammatory nature, is driven by the accumulation of large plasma membrane pores comprised of gasdermin family protein subunits. In different contexts of cellular homeostatic perturbations, infections and tissue damage, proteases, such as caspase-1 and caspase-4/5 play pivotal roles in pyroptosis by cleaving gasdermins. Gasdermin-D (GSDMD), the most extensively studied member of the gasdermin protein family, is expressed in various immune cells and certain epithelial cells. Upon cleavage by caspases, GSDMD oligomerizes and forms transmembrane pores in the cell membrane, leading to release of pro-inflammatory cytokines. GSDMD-N, the N-terminal fragment, displays an affinity for specific lipids, contributing to its role in pore formation in pyroptosis. While GSDMD is the primary focus, other gasdermin family members are also discussed in detail. These proteins exhibit distinct tissue-specific functions and contribute to different facets of cell death regulation. Additionally, genetic variations in some gasdermins have been linked to diseases, underscoring their clinical relevance. Furthermore, the interplay between GSDM pores and activation of other effectors, such as ninjurin-1 is elucidated, providing insights into the complexity of pyroptosis. The findings underscore the molecular mechanisms that govern pyroptosis and its implications for various physiological and pathological processes.

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Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC

Cited by 3 publications

References 33 publications

Insight into the Causal Relationship between Gut Microbiota and Back Pain: A Two Sample Bidirectional Mendelian Randomization Study

Insight into the Causal Relationship between Gut Microbiota and Back Pain: A Two Sample Bidirectional Mendelian Randomization Study

Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods

Pyroptosis in health and disease

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