Identifying the protective effects of miR‐874‐3p/ATF3 axis in intervertebral disc degeneration by single‐cell RNA sequencing and validation DOI Creative Commons
Xuke Wang, Qingfeng Wang,

Guowang Li

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(12)

Published: June 1, 2024

Intervertebral disc degeneration (IVDD) severely affects the work and quality of life people. We previously demonstrated that silencing activation transcription factor 3 (ATF3) blocked IVDD pathological process by regulating nucleus pulposus cell (NPC) ferroptosis, apoptosis, inflammation, extracellular matrix (ECM) metabolism. Nevertheless, whether miR-874-3p mediated targeting ATF3 remains unclear. performed single-cell RNA sequencing (scRNA-seq) bioinformatics analysis to identify as a key ferroptosis gene in IVDD. Then, Western blotting, flow cytometry, ELISA, animal experiments were validate roles regulatory mechanisms miR-874-3p/ATF3 signalling axis was highly expressed patients multiple types rat, revealed scRNA-seq analysis. GO unveiled involvement apoptosis ECM Furthermore, we verified might protect against inhibiting NPC degradation, inflammatory response ATF3. In vivo displayed protective effect on These findings propose potential biomarkers suggest may be therapeutic target for

Language: Английский

Lipid metabolism disorder promotes the development of intervertebral disc degeneration DOI Open Access

Jun Yi,

Qingluo Zhou, Jishang Huang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115401 - 115401

Published: Aug. 28, 2023

Lipid metabolism is a complex process that maintains the normal physiological function of human body. The disorder lipid has been implicated in various diseases, such as cardiovascular diseases and bone diseases. Intervertebral disc degeneration (IDD), an age-related degenerative disease musculoskeletal system, characterized by high morbidity, treatment cost, chronic recurrence. may promote pathogenesis IDD, potential mechanisms are complex. Leptin, resistin, nicotinamide phosphoribosyltransferase (NAMPT), fatty acids, cholesterol while lipocalin, adiponectin, progranulin (PGRN) exhibit protective activity against IDD development. contributes to extracellular matrix (ECM) degradation, cell apoptosis, cartilage calcification intervertebral discs (IVDs) activating inflammatory responses, endoplasmic reticulum (ER) stress, oxidative stress inhibiting autophagy. Several lines agents have developed target disorder. Inhibition be effective strategy for therapeutic management IDD. However, in-depth understanding molecular mechanism promoting development still needed.

Language: Английский

Citations

24
Discogenic Low Back Pain: Anatomic and Pathophysiologic Characterization, Clinical Evaluation, Biomarkers, AI, and Treatment Options DOI Open Access
Matteo De Simone, Anis Choucha, Elena Ciaglia

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(19), P. 5915 - 5915

Published: Oct. 3, 2024

Discogenic low back pain (LBP) is a significant clinical condition arising from degeneration of the intervertebral disc, common yet complex cause chronic pain, defined by fissuring in annulus fibrosus resulting vascularization growing granulation tissue and growth nociceptive nerve fibers along laceration area. This paper delves into anatomical pathophysiological underpinnings discogenic LBP, emphasizing role disc onset pain. The pathogenesis multifactorial, involving processes like mitochondrial dysfunction, accumulation advanced glycation end products, pyroptosis, all contributing to subsequent Despite its prevalence, diagnosing LBP challenging due overlapping symptoms with other forms absence definitive diagnostic criteria. Current approaches include evaluations, imaging techniques, exploration potential biomarkers. Treatment strategies range conservative management, such as physical therapy pharmacological interventions, more invasive procedures spinal injections surgery. Emerging therapies targeting molecular pathways involved are under investigation hold for future application. highlights necessity multidisciplinary approach combining clinical, imaging, data enhance accuracy diagnosis effectiveness treatment ultimately aiming improve patient outcomes.

Language: Английский

Citations

8
Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles DOI Creative Commons
Shanfeng Chen,

Yiming Dou,

Yiming Zhang

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 44 - 55

Published: Jan. 1, 2025

Language: Английский

Citations

1
Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases DOI Creative Commons
Hong Li, Peng Zhang, Minghui Lin

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 12, 2025

Bone-related diseases impact a large portion of the global population and, due to their high disability rates and limited treatment options, pose significant medical economic challenges. Mesenchymal stem cells (MSCs) can differentiate into multiple cell types offer strong regenerative potential, making them promising for treating various diseases. However, issues with immune response survival limit effectiveness transplantation. This has led increased interest in cell-free therapy, particularly use exosomes, which is most studied form this approach. Exosomes are extracellular vesicles that contain proteins, lipids, nucleic acids play key role communication material exchange. Pyroptosis, death involved innate immunity, also associated many Studies have shown MSC-derived exosomes therapeutic potential range conditions by regulating inflammation pyroptosis. study explored modulating pyroptosis improve bone-related

Language: Английский

Citations

1
Deep Learning Model for Grading and Localization of Lumbar Disc Herniation on Magnetic Resonance Imaging DOI
Yefu Xu, S. J. Zheng,

Qingyi Tian

et al.

Journal of Magnetic Resonance Imaging, Journal Year: 2024, Volume and Issue: unknown

Published: April 27, 2024

Background Methods for grading and localization of lumbar disc herniation (LDH) on MRI are complex, time‐consuming, subjective. Utilizing deep learning (DL) models as assistance would mitigate such complexities. Purpose To develop an interpretable DL model capable localizing LDH. Study Type Retrospective. Subjects 1496 patients (M/F: 783/713) were evaluated, randomly divided into training (70%), validation (10%), test (20%) sets. Field Strength/Sequence 1.5T axial T2‐weighted sequences (spin echo). Assessment The set was annotated by three spinal surgeons using the Michigan State University classification to train model. a surgery expert (as ground truth labels), two (comparison with trained model). An external employed evaluate generalizability Statistical Tests Calculated intersection over union (IoU) detection consistency, utilized Gwet's AC1 assess interobserver agreement, evaluated performance based sensitivity specificity, statistical significance at P < 0.05. Results achieved high consistency in both internal dataset (grading: mean IoU 0.84, recall 99.6%; localization: 0.82, 99.5%) 0.72, 98.0%; 0.71, 97.6%). For testing, 0.81; 0.76), Rater 1 (0.88; 0.82), 2 (0.86; 0.83) demonstrated results highly consistent labels. overall 87.0% 84.0% localization, while specificity 95.5% 94.4%. showed appreciable decrease 0.69; 0.66), (77.2%; 76.7%), (92.3%; 91.8%). Data Conclusion capabilities closely resemble those surgeons. future improvement, enriching diversity cases could enhance model's generalization. Level Evidence 4. Technical Efficacy Stage 2.

Language: Английский

Citations

5
Static magnetic field-modulated mesenchymal stem cell-derived mitochondria-containing microvesicles for enhanced intervertebral disc degeneration therapy DOI Creative Commons
Pengzhi Shi, Haiyang Gao, Zhangrong Cheng

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 31, 2024

Abstract Intervertebral disc degeneration (IVDD) is characterized by the senescence and declining vitality of nucleus pulposus cells (NPCs), often driven mitochondrial dysfunction. This study elucidates that mesenchymal stem (MSCs) play a crucial role in attenuating NPC secreting mitochondria-containing microvesicles (mitoMVs). Moreover, it demonstrates static magnetic fields (SMF) enhance secretion mitoMVs MSCs. By distinguishing mitoMV generation from exosomes, this shifts focus to understanding molecular mechanisms SMF intervention, emphasizing cargo transport plasma membrane budding processes, with RNA sequencing indicating potential involvement microtubule-based protein Kif5b. The further confirms interaction between Rab22a Kif5b, revealing Rab22a’s sorting into (MVs) potentially mediating subsequent budding. Subsequent construction gelatin methacrylate (GelMA) hydrogel delivery system addresses challenges vivo application verifies substantial delaying IVDD. research not only sheds light on intricacies SMF-enhanced but also provides innovative perspectives for future IVDD therapeutic strategies.

Language: Английский

Citations

5
Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization DOI Creative Commons
Chao Yu, Jing Zhao, Feng Cheng

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that novel circATXN1 highly accumulates aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell to cytoplasm expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate potential siRNA targeting backsplice junction circATNX1 was screened delivered tetrahedral framework nucleic acids (tFNAs) due unique compositional structural features. Our delivery system demonstrates superior abilities transfect cells, clear intracellular ROS, enhanced biological safety. Using siRNA–tFNAs silence NPCs exhibit reduced mislocalization up-regulation IGF-1R, thereby demonstrating rejuvenated phenotype improved function. In vivo, administering an cell-adapted acid pathologically expressed premature mice (zmpste24 −/− ) can ameliorate tissue, effectively delaying This study only functioning as senescence promoter IVDD first time, but also successfully demonstrated its via tFNA-based strategy.

Language: Английский

Citations

4
The Three-Step Approach for Lumbar Disk Herniation with Anatomical Insights Tailored for the Next Generation of Young Spine Surgeons DOI Open Access
Giuseppe La Rocca, Gianluca Galieri, Edoardo Mazzucchi

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(12), P. 3571 - 3571

Published: June 18, 2024

Background/Objectives: Lumbar disc herniation, a complex challenge in spinal health, significantly impacts individuals across diverse age groups. This article delves into the intricacies of this condition, emphasising pivotal role anatomical considerations its understanding and management. Additionally, lumbar discectomy might be considered an “easy” surgery; nevertheless, it carries significant risks. The aim study was to present groundbreaking “three-step approach” with some insight derived from our comprehensive clinical experiences, designed systematise surgical approach optimise outcomes, especially for young spine surgeons. We highlighted purpose introduced research question(s) context surrounding them. Methods: retrospective involved patients treated herniation at single institution. patient demographics, details, postoperative assessments were meticulously recorded. All surgeries performed by consistent team. Results: A total 847 998 initially included completed follow-up period. three-step every patient. recurrence rate 1.89%. Furthermore, incidence instability need reoperation carefully examined, presenting holistic view outcomes. Conclusions: emerged as robust effective strategy addressing herniation. structured ensures safe educational experience

Language: Английский

Citations

4
PRDM1 promotes nucleus pulposus cell pyroptosis leading to intervertebral disc degeneration via activating CASP1 transcription DOI Creative Commons
Cheng Yu, Jianjun Li,

Wenhao Kuang

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Oct. 21, 2024

Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain and poses considerable burden society. However, the molecular mechanisms underlying IVDD remain be elucidated. PR/SET domain 1 (PRDM1) regulates cell proliferation, apoptosis, inflammatory responses in various diseases. Despite these regulatory functions, mechanism of action PRDM1 remains unexplored. In this study, we investigated role progression. The expression nucleus pulposus (NP) tissues NP cells (NPCs) was assessed using western blotting, immunohistochemistry, immunofluorescence. effects on progression were vitro vivo. Mechanistically, mRNA sequencing, chromatin immunoprecipitation, dual-luciferase reporter assays performed confirm that triggered CASP1 transcription. Our study demonstrated for first time substantially upregulated degenerated NPCs. overexpression promoted NPCs pyroptosis by inhibiting mitophagy exacerbating progression, whereas silencing exerted opposite effect. Furthermore, activated transcription, thereby promoting vitro. Notably, reversed To best our knowledge, demonstrate inhibits repressing which may promising new therapeutic target IVDD.

Language: Английский

Citations

4
Harnessing Anti-Inflammatory and Regenerative Potential: GelMA Hydrogel Loaded with IL-10 and Kartogenin for Intervertebral Disc Degeneration Therapy DOI
Shaofeng Yang, Jinhui Shi, Yusen Qiao

et al.

ACS Biomaterials Science & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Intervertebral disc degeneration (IVDD) is a major contributor to chronic back pain and disability, with limited effective therapeutic options. Current treatment options, including conservative management surgical interventions, often fail effectively halt disease progression come notable side effects. IVDD characterized by the breakdown of extracellular matrix (ECM) infiltration inflammatory cells, which exacerbate degeneration. This study presents novel strategy aimed at addressing dual challenges inflammation ECM degradation in IVDD. We developed gelatin methacryloyl (GelMA) hydrogel system loaded interleukin-10 (IL-10), an anti-inflammatory cytokine, kartogenin (KGN), small-molecule compound known for its regenerative properties. The KGN + IL-10@GelMA was designed deliver these agents controlled manner directly degenerated disc, targeting both microenvironment promotion nucleus pulposus (NP) tissue regeneration. In puncture-induced model, this delayed degenerative facilitated NP Our findings suggest that holds significant potential as nonsurgical option IVDD, offering promising approach mitigate enhance repair.

Language: Английский

Citations

0