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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Multiple nano-drug delivery systems for intervertebral disc degeneration: Current status and future perspectives

Bioactive Materials, Journal Year: 2022, Volume and Issue: 23, P. 274 - 299

Published: Nov. 20, 2022

Low back pain (LBP) is a common disease that imposes huge social and economic burden on people. Intervertebral disc (IVD) degeneration (IVDD) often considered to be the leading cause of LBP further aggravate serious spinal problems. The established treatment strategy for IVDD consists physiotherapy, medication by drug therapy, and, if necessary, surgery, but none them can treated from etiology; is, it cannot fundamentally reverse IVD reconstruct mechanical function spine. With development nanotechnology regenerative medicine, nano-drug delivery systems (NDDSs) have improved results because their good biodegradability, biocompatibility, precise targeted specific delivery, prolonged release time, enhanced efficacy, various new NDDSs drugs, proteins, cells, genes brought light hope IVDD. This review summarizes research progress in provides prospects using address challenges We ideas generated this will provide insight into

Language: Английский

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Cellular senescence – Molecular mechanisms of intervertebral disc degeneration from an immune perspective

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114711 - 114711

Published: April 20, 2023

Intervertebral disc degeneration (IVDD) is a frequent and intractable chronic condition in orthopedics that causes enormous discomfort patients' lives thoughts, as well significant economic burden on society the nation. As result, understanding pathophysiology of IVDD critical. The has been linked to numerous variables, including oxidative stress, apoptosis, matrix metalloproteinases, inflammatory factors. Cellular senescence recently attracted lot attention study age-related diseases. It discovered intimately human senescence, which nucleus pulposus cell may play role. Previously, our group did comprehensive systematic clarification pathogenesis from an immune perspective fundamental upregulation death caused by imbalance microenvironment. In this review, we will treat novelty point clarify further explore probable relationship between immunity along with dysregulation immunological microenvironment propose new therapeutic approaches for IVDD.

Language: Английский

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Revolutionizing the treatment of intervertebral disc degeneration: an approach based on molecular typing

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 25, 2025

Intervertebral disc degeneration (IVDD) is a significant cause of global disability, reducing labor productivity, increasing the burden on public health, and affecting socio-economic well-being. Currently, there lack recognized clinical approaches for molecular classification precision therapy. Chondrocyte differentiation prognosis-related genes were extracted from single-cell RNA sequencing multi-omics data in Gene Expression Omnibus (GEO) database through chondrocyte trajectory analysis non-parametric tests. Subsequently, precise IVDD risk stratification system was developed using ConsensusClusterPlus analysis. The significance typing demonstrated case–control trials involving patients. Specific inhibitors predicted pRRophetic package R language then validated vitro. A stratified model IVDD, considering demonstrating high relevance, set 44 fate genes. Extensive analyses confirmed relevance this model, indicating that cases High Scoring Classification (HCSC) group had most favorable prognosis, whereas those Low (LCSC) worst prognosis. Additionally, studies provided evidence utility translational medicine. gene expression-based approach used to create matrix identifying potential specific each subtype. In vitro experiments revealed gefitinib, drug designed LCSC, not only protective effects chondrocytes but also could induce conversion LCSC into HCSC subgroup. Therefore, played critical role assisting clinicians with enabling personalized treatment decisions. results study have comprehensive clinically relevant offers new opportunity customizing treatments IVDD.

Language: Английский

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Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: Review

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(13), P. 7306 - 7306

Published: June 30, 2022

Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as whole. IVDD occurs result aging, mechanical trauma, lifestyle factors, certain genetic abnormalities, leads to loss nucleus pulposus, alteration in the composition extracellular matrix, excessive oxidative stress, inflammation intervertebral disc. Pharmacological surgical interventions are considered boon for treatment IVDD, but effectiveness those strategies limited. Mesenchymal stem cells (MSCs) have recently emerged possible promising regenerative therapy due their paracrine effect, restoration degenerated cells, capacity differentiation into cells. Recent investigations shown that pleiotropic effect MSCs not related mediated by secretion soluble factors. Early studies demonstrated MSC-derived exosomes therapeutic potential treating promoting cell proliferation, tissue regeneration, modulation inflammatory response, reduced apoptosis. This paper highlights current state field with further future developments, applications, challenges.

Language: Английский

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Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Frontiers in Bioengineering and Biotechnology, Journal Year: 2022, Volume and Issue: 10

Published: Oct. 7, 2022

Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens patients. Physical therapy only delays pain in patients but cannot eliminate the IVDD. Surgery required when patient tolerate or has severe neurological symptoms. Although surgical resection IVD decompression laminae eliminates diseased segment, it damages adjacent normal IVD. There also risk re-protrusion after removal. Cell played crucial role development regenerative medicine. transplantation promotes regeneration degenerative tissue. However, owing lack vascular structure IVD, sufficient nutrients be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead release harmful substances that aggravate Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain potential serve carriers deliver their contents target regulate cell activity. Owing double-layered membrane structure, low immunogenicity no immune rejection. Therefore, are considered modality they limited mass production loading rates. this review, advantages introduced, application MSC-EVs IVDD discussed. The current limitations future applications described.

Language: Английский

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Exosome-laden injectable self-healing hydrogel based on quaternized chitosan and oxidized starch attenuates disc degeneration by suppressing nucleus pulposus senescence

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 232, P. 123479 - 123479

Published: Jan. 30, 2023

Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with severity of disc degeneration, exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due their prominent antibacterial capacity, biocompatibility, biodegradability, developed an Exos-laden hydrogel based on quaternized chitosan (QCS) oxidized starch (OST) treat degeneration. The synthesized QCS-OST injectable, self-healing, biocompatible, demonstrated desirable pore size, injectable properties, sustainable release Exos. In a rat model QCS-OST/Exos able rejuvenate senescence, promote ECM remodeling, partially restore structures annulus fibrosis. Our findings suggested that novel therapeutic strategy for treating via alleviating senescence.

Language: Английский

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Hypoxia‐Preconditioned BMSC‐Derived Exosomes Induce Mitophagy via the BNIP3–ANAX2 Axis to Alleviate Intervertebral Disc Degeneration

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 8, 2024

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics autophagic flux. This study finds that absence BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) associated with senescence-related NPC degeneration, disrupting quality control. Bone marrow mesenchymal stem (BMSCs) have multidirectional differentiation potential produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich NPCs, thereby alleviating aging-associated flux, promoting damaged clearance, restoring Mechanistically, BNIP3 shown interact membrane-bound annexin A2 (ANXA2), enabling liberation transcription factor EB (TFEB) from ANXA2-TFEB complex, TFEB nuclear translocation, regulating autophagy lysosomal gene activation. Furthermore, rat model IVDD established verified vivo efficacy exosomes repairing injuries, delaying aging, matrix (ECM) synthesis. In summary, hypoxia-induced BMSC alleviate by activating BNIP3/ANXA2/TFEB axis, providing new target for treatment.

Language: Английский

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Role of oxidative stress in mitochondrial dysfunction and their implications in intervertebral disc degeneration: Mechanisms and therapeutic strategies

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 49, P. 181 - 206

Published: Oct. 16, 2024

Language: Английский

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Lumbar instability remodels cartilage endplate to induce intervertebral disc degeneration by recruiting osteoclasts via Hippo-CCL3 signaling

Bone Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: May 30, 2024

Degenerated endplate appears with cheese-like morphology and sensory innervation, contributing to low back pain subsequently inducing intervertebral disc degeneration in the aged population.

Language: Английский

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