Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions

Bone Research, Journal Year: 2021, Volume and Issue: 9(1)

Published: Jan. 29, 2021

Abstract Low back pain (LBP), as a leading cause of disability, is common musculoskeletal disorder that results in major social and economic burdens. Recent research has identified inflammation related signaling pathways important factors the onset progression disc degeneration, significant contributor to LBP. Inflammatory mediators also play an indispensable role discogenic The suppression LBP primary goal clinical practice but not received enough attention studies. Here, overview advances inflammation-related degeneration provided, with discussion on IVD induction. Puncture models, mechanical spontaneous models main animal study painful are discussed, underlying summarized. Furthermore, potential drug candidates, either under laboratory investigation or undergoing trials, suppress by eliminating explored. We hope attract more interest address IDD contribute promoting translational research.

Language: Английский

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Mitophagy in degenerative joint diseases

Autophagy, Journal Year: 2020, Volume and Issue: 17(9), P. 2082 - 2092

Published: Sept. 24, 2020

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis function important. Mitophagy, a process that selectively clears damaged or dysfunctional through autophagic machinery, functions to maintain mitochondrial quality control homeostasis. IVDD OA are similar joint diseases involving degradation cartilaginous tissues mainly caused by oxidative stress, cell apoptosis extracellular matrix (ECM) degradation. Over past decade, accumulating evidence indicates essential role mitophagy pathogenesis OA. Importantly, strategies regulation exert beneficial effects pre-clinical experiments. Given importance novelty mitophagy, we provide an overview pathways discuss roles We also highlight potential targeting for treatment diseases.Abbreviations: AD: Alzheimer disease; AF: annulus fibrosus; ADORA2A/A2AR: adenosine A2a receptor; AMBRA1: autophagy beclin 1 regulator 1; BMSCs: bone marrow mesenchymal stem cells; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B 3-like; CDH6: cadherin 6; CEP: endplates; circRNA: circular RNA; DNM1L/DRP1: dynamin 1-like; ECM: matrix; HIF1A: hypoxia inducible factor 1: alpha subunit; IL1B: interleukin beta; IMM: inner membranes; IVDD: degeneration; MAPK8/JNK: mitogen-activated kinase 8; MFN1: mitofusin MFN2: 2; MIA: monosodium iodoacetate; RHOT/MIRO: ras homolog family member T; MMP: transmembrane potential; CALCOCO2/NDP52: calcium binding coiled-coil domain NFE2L2: nuclear factor: erythroid 2 like NP: nucleus pulposus; OA: osteoarthritis; OPA1: GTPase; OPTN: optineurin; PRKN: parkin RBR E3 ubiquitin ligase; PD: Parkinson PGAM5: PGAM 5; PPARGC1A/PGC-1A: peroxisome proliferator activated receptor: gamma: coactivator alpha; PHF23: PHD finger 23; PINK1: PTEN induced putative ROS: reactive oxygen species; SfMSCs: synovial fluid MSCs; SIRT1: sirtuin SIRT2: SIRT3: SQSTM1/p62: sequestosome TNF: tumor necrosis factor; Ub: ubiquitin; UBL: ubiquitin-like; VDAC: voltage-dependent anion channel.

Language: Английский

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Is Melatonin the Cornucopia of the 21st Century?

Antioxidants, Journal Year: 2020, Volume and Issue: 9(11), P. 1088 - 1088

Published: Nov. 5, 2020

Melatonin, an indoleamine hormone produced and secreted at night by pinealocytes extra-pineal cells, plays important role in timing circadian rhythms (24-h internal clock) regulating the sleep/wake cycle humans. However, recent years melatonin has gained much attention mainly because of its demonstrated powerful lipophilic antioxidant free radical scavenging action. Melatonin been proven to be twice as active vitamin E, believed most effective antioxidant. Melatonin-induced signal transduction through receptors promotes expression enzymes well inflammation-related genes. also exerts immunomodulatory action stimulation high-affinity expressed immunocompetent cells. Here, we reviewed efficacy, safety side effects supplementation treating oxidative stress- and/or disorders, such obesity, cardiovascular diseases, immune infectious cancer, neurodegenerative osteoporosis infertility.

Language: Английский

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Oxidative stress in intervertebral disc degeneration: Molecular mechanisms, pathogenesis and treatment

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(9)

Published: March 13, 2023

Abstract Low back pain (LBP) is a leading cause of labour loss and disability worldwide, it also imposes severe economic burden on patients society. Among symptomatic LBP, approximately 40% caused by intervertebral disc degeneration (IDD). IDD the pathological basis many spinal degenerative diseases such as herniation stenosis. Currently, therapeutic approaches for mainly include conservative treatment surgical treatment, neither which can solve problem from root terminating process (IVD). Therefore, further exploring pathogenic mechanisms adopting targeted strategies one current research hotspots. complex pathophysiological processes IDD, oxidative stress considered main factor. The delicate balance between reactive oxygen species (ROS) antioxidants essential maintaining normal function survival IVD cells. Excessive ROS levels damage to macromolecules nucleic acids, lipids, proteins cells, affect cellular activities functions, ultimately lead cell senescence or death. This review discusses potential role in understand provides IDD.

Language: Английский

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Causes of and Molecular Targets for the Treatment of Intervertebral Disc Degeneration: A Review

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 394 - 394

Published: Jan. 24, 2022

Intervertebral disc degeneration (IVDD) is a pathological condition that can lead to intractable back pain or secondary neurological deficits. There no fundamental cure for this condition, and current treatments focus on alleviating symptoms indirectly. Numerous studies have been performed date, the major strategy all of IVDD prevent cell loss due programmed regulated death. Accumulating evidence suggests several types death other than apoptosis, including necroptosis, pyroptosis, ferroptosis, are also involved in IVDD. In study, we discuss molecular pathway each type review literature has identified their role We summarize recent advances targeted therapy at RNA level, modulations through interference regulation non-coding RNAs, preventing subsequent Therefore, causes possible therapeutic targets intervention future direction research field.

Language: Английский

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Single-Cell RNA-Seq Analysis of Cells from Degenerating and Non-Degenerating Intervertebral Discs from the Same Individual Reveals New Biomarkers for Intervertebral Disc Degeneration

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3993 - 3993

Published: April 3, 2022

In this study, we used single-cell transcriptomic analysis to identify new specific biomarkers for nucleus pulposus (NP) and inner annulus fibrosis (iAF) cells, define cell populations within non-degenerating (nD) degenerating (D) human intervertebral discs (IVD) of the same individual. Cluster based on differential gene expression delineated 14 clusters. Gene profiles at resolution revealed potential functional differences linked degeneration, among NP iAF subpopulations. GO KEGG analyses discovered molecular functions, biological processes, transcription factors type degeneration state. We propose two lists biomarkers, one as type, including C2orf40, MGP, MSMP, CD44, EIF1, LGALS1, RGCC, EPYC, HILPDA, ACAN, MT1F, CHI3L1, ID1, ID3 TMED2. The second list proposes predictive IVD genes, MT1G, SPP1, HMGA1, FN1, FBXO2, SPARC, VIM, CTGF, MGST1, TAF1D, CAPS, SPTSSB, S100A1, CHI3L2, PLA2G2A, TNRSF11B, FGFBP2, SLPI, DCN, MT-ND2, MTCYB, ADIRF, FRZB, CLEC3A, UPP1, S100A2, PRG4, COL2A1, SOD2 MT2A. Protein mRNA vimentin, SYF2 (p29) genes validated our scRNA-seq findings. Our data provide insights into disc cells phenotypes that could improve diagnostic therapeutic options.

Language: Английский

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Intervertebral disc degeneration—Current therapeutic options and challenges

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: July 6, 2023

Degeneration of the intervertebral disc (IVD) is a normal part aging. Due to spine's declining function and development pain, it may affect one's physical health, mental socioeconomic status. Most degeneration (IVDD) therapies today focus on symptoms low back pain rather than underlying etiology or mechanical disc. The deteriorated typically not restored by conservative surgical that largely correcting structural abnormalities. To enhance clinical outcome quality life patient, several therapeutic modalities have been created. In this review, we discuss genetic environmental causes IVDD describe promising modern endogenous exogenous approaches including their applicability relevance process.

Language: Английский

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The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102323 - 102323

Published: May 9, 2024

Oxidative stress is one of the main driving mechanisms intervertebral disc degeneration(IDD). has been associated with inflammation in disc, cellular senescence, autophagy, and epigenetics cells. It above pathological are closely linked through common hub reactive oxygen species(ROS), promote each other process degeneration development disease. This reveals important role oxidative IDD, importance great potential IDD therapy targeting stress. The efficacy traditional unstable or cannot be maintained. In recent years, due to rise materials science, many bioactive functional have applied treatment combination drugs, satisfactory achieved. At present, research review antioxidant not complete. Based on existing studies, mechanism were summarized this paper, strategies based emerging reviewed.

Language: Английский

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Melatonin modulates IL-1β-induced extracellular matrix remodeling in human nucleus pulposus cells and attenuates rat intervertebral disc degeneration and inflammation

Aging, Journal Year: 2019, Volume and Issue: 11(22), P. 10499 - 10512

Published: Nov. 26, 2019

The inflammatory-associated factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are widely reported to be associated with intervertebral disc (IVD) degeneration (IVDD). N-acetyl-5-methoxytryptamine (melatonin) is a natural hormone secreted by the pineal gland which has been shown participate in several physiological pathological progresses, such as aging, anti-inflammation, anti-apoptosis autophagy regulation. However, effects of melatonin on IVD remain unclear. In present study, we treated human nucleus pulposus cells (NPCs) discovered that could modulate extracellular matrix (ECM) remodeling induced IL-1β enhancing collagen II aggrecan expression levels downregulating metalloproteinase-3 (MMP-3) levels. These findings were verified western blot immunofluorescence assays. Intraperitoneal injection mitigated IVDD rat tail puncture model. X-ray magnetic resonance imaging (MRI), well hematoxylin-eosin (H&E), Safranine O-Green, Alcian blue Celium red staining methods adopted evaluate grades, structural integrity (NP) annulus fibrosus (AF) damage calcification cartilage endplate. Melatonin reduced inflammatory cell aggregation release IL-1β, IL-6, TNF-α determined immunohistochemistry. conclusion, study demonstrated ECM vitro attenuate induction inflammation model vivo. data may contribute restoration processs following used potential novel therapy for IVDD.

Language: Английский

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CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

Cell Death and Disease, Journal Year: 2019, Volume and Issue: 10(10)

Published: Oct. 3, 2019

Language: Английский

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