Cartilaginous endplates: A comprehensive review on a neglected structure in intervertebral disc research

JOR Spine, Год журнала: 2023, Номер 6(4)

Опубликована: Окт. 21, 2023

Abstract The cartilaginous endplates (CEP) are key components of the intervertebral disc (IVD) necessary for sustaining nutrition while distributing mechanical loads and preventing from bulging into adjacent vertebral body. size, shape, composition CEP essential in maintaining its function, degeneration is considered a contributor to early IVD degeneration. In addition, implicated Modic changes, which often associated with low back pain. This review aims tackle current knowledge regarding structure, composition, permeability, role healthy disc, how they change degeneration, connect Additionally, authors suggest standardized naming convention bony endplate avoiding term endplate. Currently, there limited data on itself as reported combination endplate, or articular cartilage. However, it clear unique tissue type that differs cartilage, other tissues. Thus, future research should investigate separately fully understand degenerated IVDs. Further, most regeneration therapies development failed address, even CEP, despite stability within IVD. be potentially targeted sustainable treatments.

Язык: Английский

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The role of ferroptosis in intervertebral disc degeneration

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Июль 27, 2023

Nucleus pulposus, annulus fibrosus, and cartilage endplate constitute an avascular intervertebral disc (IVD), which is crucial for spinal joint mobility. As one of the most widespread health issues worldwide, degeneration (IVDD) recognized as a key contributor to back neck discomfort. A number degenerative disorders have strong correlation with ferroptosis, recently identified novel regulated cell death (RCD) characterized by iron-dependent mechanism buildup lipid reactive oxygen species (ROS). There growing interest in part ferroptosis plays IVDD pathophysiology. Inhibiting has been shown control development. Several studies demonstrated that TBHP-induced oxidative stress models, changes marker protein levels increased peroxidation lead cells, subsequently aggravates IVDD. Similarly, significantly relieved use inhibitors. The purpose this review was threefold: 1) discuss occurrence IVDD; 2) understand its role pathophysiology; 3) investigate feasibility prospect treatment.

Язык: Английский

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M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Май 31, 2024

Abstract Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown significance M1-type macrophages in IVDD; nevertheless, precise mechanism route it influences function nucleus pulposus cell (NPC) remain unknown. Utilizing rat acupuncture model an NPC induced lipopolysaccharide (LPS), we investigated M1 macrophage-derived exosomes (M1-Exos) both vivo vitro this study. We found that M1-Exos enhanced LPS-induced senescence, increased number SA-β-gal-positive blocked cycle, promoted activation P21 P53. derived from supernatant pretreated with exosome inhibitor GW4869 reversed result vitro. RNA-seq showed Lipocalin2 (LCN2) was enriched targeted NF-κB pathway. The quantity cells significantly reduced inhibition LCN2, expression P53 NPCs decreased. same results were obtained acupuncture-induced model. In addition, LCN2 promotes type II collagen (Col-2) inhibits matrix metalloproteinase 13 (MMP13), thereby restoring equilibrium metabolism inside extracellular (ECM) vivo. pathway crucial for regulating M1-Exo-mediated senescence. After addition LPS-treated NPCs, p-p65 activity activated, while si-LCN2 treatment inhibited activity. Therefore, paper demonstrates ability deliver activates signaling pathway, exacerbates accelerating This shed new light on bring fresh approach therapy. Graphical

Язык: Английский

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A new strategy for intervertebral disc regeneration: The synergistic potential of mesenchymal stem cells and their extracellular vesicles with hydrogel scaffolds

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 172, С. 116238 - 116238

Опубликована: Фев. 3, 2024

Intervertebral disc degeneration (IDD) is a disease that severely affects spinal health and prevalent worldwide. Mesenchymal stem cells (MSCs) their derived extracellular vesicles (EVs) have regenerative potential emerged as promising therapeutic tools for treating degenerative discs. However, challenges such the harsh microenvironment of degenerated intervertebral discs EVs' limited stability efficacy hindered clinical application. In recent years, hydrogels attracted much attention in field IDD therapy because they can mimic physiologic provide solution by providing suitable growth environment MSCs EVs. This review introduced biological properties EVs, summarized research on application EVs IDD, current trial studies also explored mechanism action addition, plenty elaborated different classified tissue engineering, synergistic effect promoting regeneration, wide IDD. Finally, problems still faced hydrogel-loaded treatment are summarized, solutions proposed. paper outlines effects combination with aims to theoretical references future related studies.

Язык: Английский

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Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles

Journal of Orthopaedic Translation, Год журнала: 2025, Номер 50, С. 44 - 55

Опубликована: Янв. 1, 2025

Язык: Английский

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Autophagy activation alleviates annulus fibrosus degeneration via the miR-2355-5p/mTOR pathway

Journal of Orthopaedic Surgery and Research, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 23, 2025

Язык: Английский

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FUS-induced circRHOBTB3 facilitates cell proliferation via miR-600/NACC1 mediated autophagy response in pancreatic ductal adenocarcinoma

Journal of Experimental & Clinical Cancer Research, Год журнала: 2021, Номер 40(1)

Опубликована: Авг. 20, 2021

Circular RNAs (circRNAs) are becoming a unique member of non-coding (ncRNAs) with emerging evidence their regulatory roles in various cancers. However, regards to pancreatic ductal adenocarcinoma (PDAC), circRNAs biological functions remain largely unknown and worth investigation for potential therapeutic innovation.In our previous study, next-generation sequencing was used identify differentially expressed 3 pairs PDAC adjacent normal tissues. Further validation circRHOBTB3 expression tissues cell lines gain-and-loss function experiments verified the oncogenic role circRHOBTB3. The mechanism validated by pull-down assays, RIP, luciferase reporter assays. autophagy response PANC-1 MiaPaca-2 cells were detected mCherry-GFP-LC3B labeling confocal microscopy, transmission electron microscopy protein levels LC3B or p62 via Western blot.circRHOBTB3 is highly tissues, which also promotes then progression vitro vivo. Mechanistically, directly binds miR-600 subsequently acts as miRNA-sponge maintain level miR-600-targeted gene NACC1, facilitates adaptation proliferation Akt/mTOR pathway. Moreover, RNA-binding FUS (FUS) pre-RHOBTB3 mRNA mediate biogenesis Clinically, circRHOBTB3, NACC1 correlated prognosis patients serve independent risk factors patients.FUS-mediated tumor activator promote modulating miR-600/NACC1/Akt/mTOR axis regulated autophagy.

Язык: Английский

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Oxidative Stress and Intervertebral Disc Degeneration: Pathophysiology, Signaling Pathway, and Therapy

Oxidative Medicine and Cellular Longevity, Год журнала: 2022, Номер 2022, С. 1 - 14

Опубликована: Окт. 10, 2022

Intervertebral disc degeneration (IDD), characterized as decreased proteoglycan content, ossification of endplate, and intervertebral height, is one the major reasons low back pain, which seriously affects quality life also brings heavy economic burden. However, mechanisms leading to IDD its therapeutic targets have not been fully elucidated. Oxidative stress refers imbalance between oxidation antioxidant systems, too many products reactive oxygen species (ROS) insufficient scavenging function. Excessive ROS can damage cell lipids, nucleic acids proteins, has proved be related development a variety diseases. In recent years, an increasing number studies reported that oxidative involved in pathological process IDD. accelerate via inducing activities, such inflammation, apoptosis, senescence. this review, we focused on pathophysiology molecular stress-induced Moreover, present review summarized possible ideas for future therapy strategies stress-related

Язык: Английский

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Hesperidin mitigates oxidative stress-induced ferroptosis in nucleus pulposus cells via Nrf2/NF-κB axis to protect intervertebral disc from degeneration

Cell Cycle, Год журнала: 2023, Номер 22(10), С. 1196 - 1214

Опубликована: Апрель 13, 2023

Intervertebral disc degeneration (IVDD), a widely known contributor to low back pain (LBP), has been proved be global health challenging conundrum. Hesperidin (hesperetin-7-O-rutinoside, HRD) is flavanone glycoside that belongs the subgroup of citrus flavonoids with therapeutic effect on various diseases due its anti-inflammatory, antioxidant properties. However, HRD IVDD remains elusive. The human nucleus pulposus tissues were harvested for isolating (HNP) cells verify expression Nrf2. biological HNP assessed in vitro, and vivo effects mice. Firstly, we found Nrf2 was decreased progression degenerated tissue. Subsequently, confirmed could mitigate oxidative stress-induced ferroptosis via enhancing axis suppressing NF-κB pathway protect intervertebral from vitro. Finally, vivo. current study first time may by an stress-dependent pathway. evidence will provide possible basis future targeted treatment IVDD.

Язык: Английский

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Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects

Journal of Orthopaedic Translation, Год журнала: 2023, Номер 39, С. 74 - 87

Опубликована: Янв. 25, 2023

The incidence of intervertebral disc degeneration (IVDD) is a common degenerative disease with inflammation, decreased autophagy, and progression fibrosis as its possible pathogenesis. Physalin A (PA) widely studied anti-inflammatory drug. However, therapeutic effects on IVDD remain unexplored. Therefore, we aimed to explore the potential PA in progression. In vivo, investigated bioactivity using puncture-induced rat model. signals height changes were detected X-ray, micro-CT, MRI, structural molecular lesions histological staining immunohistochemistry sections. interleukin-1 beta (IL-1β) TGF-β1 employed establish inflammation fibrotic nucleus pulposus (NP) cells. effect duration, concentration, influence pathways, pathological treatment elucidated western blotting, real-time PCR, immunofluorescence. exerted significant remission due anti-inflammation, reduction, autophagy enhancement. vitro, improved by blocking NF-κB MAPK whereas it promoted via PI3K/AKT/mTOR pathway affected regulating SMAD2/3 pathway. Moreover, process exhibited anti-fibrotic vivo vitro models, thus effectively relieving progression, indicating promising agent for treatment. This study successfully reveals that PA, natural bioactive withanolide, relieved inhibition, enhancement,

Язык: Английский

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