Modern views on the pathogenesis of intervertebral disc degeneration DOI Creative Commons
N. А. Shnayder, Vera V. Trefilova, A. V. Аshkhotov

et al.

The Clinician, Journal Year: 2024, Volume and Issue: 18(1), P. 37 - 48

Published: June 24, 2024

Introduction. Intervertebral disc (IVD) degeneration is defined as a multifactorial degenerative disease of the spine, starting from structures nucleus pulposus IVD, spreading to fibrous ring and other elements spinal motion segment. Unlike natural aging, pathological process that occurs in IVDs result additive effect genetic predisposition external environmental factors leads formation chronic back pain reduces patient’s quality life. Despite many years studying problem pathogenesis IVD degeneration, it far being resolved, which encourages us further study pathogenetic mechanisms development this pathology. Aim. To update knowledge practicing neurologists about results modern studies leading humans their role promising biomarkers pathology new strategies for therapy. Materials methods. A search analysis publications was carried out Russian-language (e-Library) Englishlanguage databases (PubMed, Oxford Press, Clinical Keys, Springer, Elsevier, Google Scholar). Search depth – 5 (2018–2023). Res ults . The analyzed generalized molecular influencing progression are presented. such oxidative stress NO system, cytokine imbalance, increased activity matrix metalloproteinases, dysfunction fibrillar collagens proteoglycan, well relationship with each other, were considered. Conclusion. review provides broader look at makes possible set goals future therapeutic strategies.

Language: Английский

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study DOI Creative Commons
Qingcong Zheng, Rongjie Lin, Du Wang

et al.

JOR Spine, Journal Year: 2024, Volume and Issue: 7(2)

Published: June 1, 2024

Abstract Background Numerous investigations have suggested links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs), but causality has not been proven. This study used Mendelian randomization (MR) to investigate the causal associations 91 CIPs cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), canal stenosis (SCS), spondylolisthesis/spondylolysis. Methods Genetic variants data for SDDs were obtained from genome‐wide association studies (GWAS) database. We inverse variance weighted (IVW) as primary method, analyzing validity robustness of results through pleiotropy heterogeneity tests performing reverse MR analysis test causality. Results The IVW with Bonferroni correction indicated that beta‐nerve growth factor (β‐NGF), C‐X‐C motif chemokine 6 (CXCL6), interleukin‐6 (IL‐6) can increase risk CS. Fibroblast 19 (FGF19), sulfotransferase 1A1 (SULT1A1), tumor necrosis factor‐beta (TNF‐β) PD/SD risk, whereas urokinase‐type plasminogen activator (u‐PA) decrease PD/SD. FGF19 TNF SCS risk. STAM binding protein (STAMBP) T‐cell surface glycoprotein CD6 isoform (CD6 isoform) spondylolisthesis/spondylolysis, monocyte chemoattractant 2 (MCP2) latency‐associated peptide transforming beta 1 (LAP‐TGF‐β1) spondylolisthesis/spondylolysis Conclusions multiple genetically predicted four (CS, PD/SD, SCS, spondylolisthesis/spondylolysis). provides reliable genetic evidence in‐depth exploration involvement in pathogenic mechanism novel potential targets SDDs.

Language: Английский

Citations

7
Targeting skeletal interoception: a novel mechanistic insight into intervertebral disc degeneration and pain management DOI Creative Commons
Haijun Zhu,

J.Z. Ren,

Xiangjin Wang

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 12, 2025

Despite being a leading cause of chronic pain and disability, the underlying mechanisms intervertebral disc (IVD) degeneration (IVDD) remain unclear. Emerging evidence suggests that mechanosensation (the ability skeletal system to perceive mechanical biochemical signals) mediated by abnormal loading plays critical role in regulation IVD health. This review examines complex interactions amongIVDs, intraosseous sensory mechanisms, central nervous (CNS), with particular focus on roles pathways such as PGE2/EP4, Wnt/β-catenin, NF-κB. elucidates manner which stress aberrant signaling disrupt homeostasis nucleus pulposus (NP), cartilaginous endplate (CEP) annulus fibrosus (AF), thereby driving exacerbating pain. Furthermore, targeted therapeutic strategies, including modulation interoception dynamic loading, present novel avenues for reversing IVDD progression. By integrating biology spinal pathology, this work offers perspective pathogenesis identifies promising strategies clinical intervention. These findings highlight potential targeting mitigate associated pain, paving way innovative, mechanism-driven therapies.

Language: Английский

Citations

0
Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration DOI

Jiawen Zhan,

Yongzhi Cui, Ping Zhang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 14(2)

Published: Nov. 18, 2024

Abstract Cartilage endplate cell (CEPC) and nucleus pulposus (NPC) inflammation are critical factors that contribute to intervertebral disc degeneration (IVDD). Recent evidence indicated iron ion influx, reactive oxygen species (ROS), the cGAS‐STING pathway involved in CEPC inflammatory degeneration. Moreover, cytokines produced by degenerating CEPCs lactic acid accumulation within microenvironment significantly NPC inflammation. Consequently, simultaneous alleviation of correction acidic anticipated reverse IVDD. Herein, CEPC‐targeted engineered exosomes loaded with salvianolic A incorporated into a CaCO 3 /chitosan hydrogel, forming composite gel, CAP‐sEXOs@Gel. Notably, CAP‐sEXOs@Gel shows long local retention, realizes slow release CAP‐sEXOs specific uptake CEPCs. After CEPCs, reduce intracellular ROS inhibiting hypoxia‐inducible factor‐2α (HIF‐2α)/TfR1 expression. Iron influx inhibition maintenance normal mitochondrial function reduced mtDNA leakage, suppresing pathway. Additionally, component neutralizes H + , thereby alleviating Collectively, this novel hydrogel demonstrates ability concurrently inhibit inflammation, presenting promising therapeutic approach for

Language: Английский

Citations

3
Can extracellular vesicles be considered as a potential frontier in the treatment of intervertebral disc disease? DOI Creative Commons
S.Y. Zhu, Junlin Wang,

Moran Suo

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102094 - 102094

Published: Oct. 18, 2023

As a global public health problem, low back pain (LBP) caused by intervertebral disc degeneration (IDD) seriously affects patients' quality of life. In addition, the prevalence IDD tends to be younger, which brings huge burden individuals and society economically. Current treatments do not delay or reverse progression IDD. The emergence biologic therapies has brought new hope for treatment Among them, extracellular vesicles (EVs), as nanoscale bioactive substances that mediate cellular communication, have now produced many surprising results in research This article reviews mechanisms roles EVs delaying describes prospects challenges EVs.

Language: Английский

Citations

7
Visualizing the bibliometrics of the inflammatory mechanisms in intervertebral disc degeneration DOI Creative Commons
Nan Wang,

Weihao Rong,

Yimin Xie

et al.

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 188, P. 112380 - 112380

Published: Feb. 22, 2024

Intervertebral disc degeneration (IVDD) constitutes a crucial pathological foundation for spinal degenerative diseases (SDD) and stands as primary contributor to both low back pain (LBP) disability. The progression of IVDD is linked structural functional alterations in tissues, where an imbalance the inflammatory microenvironment can induce extracellular matrix (ECM) degradation, senescence, apoptosis. This key pathomechanism disease's development, gaining considerable attention recent years. study aims conduct bibliometric analysis publications pertaining mechanisms quantitatively assess current research hotspots directions.

Language: Английский

Citations

2
The Survival of Human Intervertebral Disc Nucleus Pulposus Cells under Oxidative Stress Relies on the Autophagy Triggered by Delphinidin DOI Creative Commons
Md Entaz Bahar,

Jin Seok Hwang,

Trang Huyen Lai

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 759 - 759

Published: June 23, 2024

Delphinidin (Delp), a natural antioxidant, has shown promise in treating age-related ailments such as osteoarthritis (OA). This study investigates the impact of delphinidin on intervertebral disc degeneration (IVDD) using human nucleus pulposus cells (hNPCs) subjected to hydrogen peroxide. Various molecular and cellular assays were employed assess senescence, extracellular matrix (ECM) degradation markers, activation AMPK autophagy pathways. Initially, oxidative stress (OS)-induced hNPCs exhibited notably elevated levels senescence markers like p53 p21, which mitigated by Delp treatment. Additionally, attenuated IVDD characteristics including apoptosis ECM OS-induced (OSIS) downregulating MMP-13 ADAMTS-5 while upregulating COL2A1 aggrecans. Furthermore, reversed increased ROS production reduced observed OSIS hNPCs. Interestingly, ability regulate balance was hindered inhibition CQ. Remarkably, upregulated SIRT1 phosphorylated expression mTOR phosphorylation presence AICAR (AMPK activator), this effect Compound C, inhibitor. In summary, our findings suggest that can safeguard from promoting through SIRT1/AMPK/mTOR pathway.

Language: Английский

Citations

1
Modern views on the pathogenesis of intervertebral disc degeneration DOI Creative Commons
N. А. Shnayder, Vera V. Trefilova, A. V. Аshkhotov

et al.

The Clinician, Journal Year: 2024, Volume and Issue: 18(1), P. 37 - 48

Published: June 24, 2024

Introduction. Intervertebral disc (IVD) degeneration is defined as a multifactorial degenerative disease of the spine, starting from structures nucleus pulposus IVD, spreading to fibrous ring and other elements spinal motion segment. Unlike natural aging, pathological process that occurs in IVDs result additive effect genetic predisposition external environmental factors leads formation chronic back pain reduces patient’s quality life. Despite many years studying problem pathogenesis IVD degeneration, it far being resolved, which encourages us further study pathogenetic mechanisms development this pathology. Aim. To update knowledge practicing neurologists about results modern studies leading humans their role promising biomarkers pathology new strategies for therapy. Materials methods. A search analysis publications was carried out Russian-language (e-Library) Englishlanguage databases (PubMed, Oxford Press, Clinical Keys, Springer, Elsevier, Google Scholar). Search depth – 5 (2018–2023). Res ults . The analyzed generalized molecular influencing progression are presented. such oxidative stress NO system, cytokine imbalance, increased activity matrix metalloproteinases, dysfunction fibrillar collagens proteoglycan, well relationship with each other, were considered. Conclusion. review provides broader look at makes possible set goals future therapeutic strategies.

Language: Английский

Citations

0