Self-assembled Antioxidant Enzyme-mimicking Hydrogel: Targeting Oxidative Stress and Macrophage Organization for Improving Degenerated Intervertebral Discs DOI Creative Commons

Fu Yudong,

Hua Sun,

Yongchao Jin

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 31, P. 101586 - 101586

Published: Feb. 20, 2025

Intervertebral disc degeneration (IVDD) is a major contributor to lower back pain. At present, antioxidant therapy regarded as one of the most promising strategies for treating IVDD, due critical role reactive oxygen species (ROS) in its pathogenesis. Herein, we presented self-assembled hydrogel, termed MnGAHs, formed through crossing manganese ions (Mn2+) and glycyrrheic acid (GA), which possessed activities enzymes, including catalase (CAT) superoxide dismutase (SOD). The obtained MnGAHs effectively scavenge ROS, reducing oxidative stress levels alleviating senescence nucleus pulposus-derived mesenchymal stem cells (NPMSC), thereby mitigating IVDD. Furthermore, also promoted macrophage polarization towards M2 phenotype, inflammatory response inhibiting progression By combining theoretical calculations with analyses public databases, revealed that ROS-p53-p21 axis played crucial function reverse finding further confirmed by Western blot analysis. As result, injection into intervertebral (IVD) significantly alleviated process rat model puncture-induced Therefore, as-prepared enzyme-mimicking hydrogels provide effective approach

Language: Английский

Pyroptosis and degenerative diseases of the elderly DOI Creative Commons
Jiamin Zhou,

Jingjing Qiu,

Yuwan Song

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 9, 2023

Abstract Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins the gasdermin family. Widely recognized signaling cascades include classical, non-classical, caspase-3-dependent E and caspase-8-dependent D pathways. Additional pyroptotic pathways have been subsequently reported. With rising prevalence advanced age, role pyroptosis in degenerative diseases elderly has attracted increased research attention. This article reviews primary mechanisms summarizes progress such as presbycusis, age-related macular degeneration, Alzheimer’s disease, intervertebral disc osteoarthritis.

Language: Английский

Citations

47
The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications DOI Creative Commons
Xiang‐Long Chen, Anran Zhang, Kangcheng Zhao

et al.

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

Citations

25
Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy DOI Creative Commons
Takashi Yurube, Yoshiki Takeoka,

Yutaro Kanda

et al.

North American Spine Society Journal (NASSJ), Journal Year: 2023, Volume and Issue: 14, P. 100210 - 100210

Published: March 11, 2023

Language: Английский

Citations

28
Mitochondrial dysfunction: a new molecular mechanism of intervertebral disc degeneration DOI
Chao Song, Yulin Xu, Qinghua Peng

et al.

Inflammation Research, Journal Year: 2023, Volume and Issue: 72(12), P. 2249 - 2260

Published: Nov. 5, 2023

Language: Английский

Citations

26
Platelet-rich plasma-derived extracellular vesicles inhibit NF-κB/NLRP3 pathway-mediated pyroptosis in intervertebral disc degeneration via the MALAT1/microRNA-217/SIRT1 axis DOI

Xueqiang Tao,

Fen Xue,

Jiayuan Xu

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 117, P. 111106 - 111106

Published: Feb. 17, 2024

Language: Английский

Citations

11
Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells DOI

Daqian Zhou,

Yongliang Mei,

Chao Song

et al.

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 54(9)

Published: April 17, 2024

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes heavy economic burden on people and society. Although it well established IVDD associated with genetic susceptibility, ageing obesity, its pathogenesis remains incompletely understood. Previously, was thought to occur because of excessive mechanical loading leading destruction nucleus pulposus cells (NPCs), but studies have shown much more complex process inflammation, metabolic factors NPCs death can involve all parts the disc, characterized by causing extracellular matrix (ECM) degradation. The damage pattern like some programmed cell death, suggesting death. apoptosis pyroptosis been studied IVDD, intervertebral still not be fully elucidated using only traditional modalities. With increasing research, new modes PANoptosis, ferroptosis senescence found closely related degeneration. Among these, PANoptosis combines essential elements pyroptosis, necroptosis form highly coordinated dynamically balanced inflammatory process. Furthermore, we believe may also crosstalk senescence. Therefore, review progress research multiple deaths provide guidance for clinical treatment.

Language: Английский

Citations

11
Injectable, self-healing hydrogels based on gelatin, quaternized chitosan, and laponite as localized celecoxib delivery system for nucleus pulpous repair DOI

Maryam Nezadi,

Hamid Keshvari, Fatemeh Shokrolahi

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 266, P. 131337 - 131337

Published: April 2, 2024

Language: Английский

Citations

10
Recent Advances in Managing Spinal Intervertebral Discs Degeneration DOI Open Access
Bogdan Costăchescu, Adelina-Gabriela Niculescu, Raluca Ioana Teleanu

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6460 - 6460

Published: June 9, 2022

Low back pain (LBP) represents a frequent and debilitating condition affecting large part of the global population posing worldwide health economic burden. The major cause LBP is intervertebral disc degeneration (IDD), complex disease that can further aggravate give rise to severe spine problems. As most current treatments for IDD either only alleviate associated symptoms or expose patients risk intraoperative postoperative complications, there pressing need develop better therapeutic strategies. In this respect, present paper first describes pathogenesis etiology set framework what has be combated restore normal state discs (IVDs), then elaborates on recent advances in managing IDD. Specifically, are reviewed bioactive compounds growth factors have shown promising potential against underlying IDD, cell-based therapies IVD regeneration, biomimetic artificial IVDs, several other emerging options (e.g., exosomes, RNA approaches, intelligence).

Language: Английский

Citations

34
The Effect of Gut Microbiota on the Progression of Intervertebral Disc Degeneration DOI Creative Commons

Bo Yao,

Youquan Cai,

Weiguo Wang

et al.

Orthopaedic Surgery, Journal Year: 2023, Volume and Issue: 15(3), P. 858 - 867

Published: Jan. 4, 2023

Intervertebral disc degeneration (IDD) is the main cause of back pain, and its treatment a serious socio-economic burden. The safety fecal microbiota transplantation (FMT) has been established. However, relationship between FMT IDD still unclear. We aimed to explore whether plays role in provide reference for IDD.An experimental model was established using 2-month-old male Sprague-Dawley rats. performed by intragastric gavage rats with bacterial solution. Rat serum, feces, vertebral tissue were collected after surgery 2 months. levels TNF-α, IL-1β, IL-6, matrix metalloproteinase (MMP)-3, MMP-13, Collagen II, aggrecan serum or measured an enzyme-linked immunosorbent assay, immunohistochemistry, quantitative real-time polymerase chain reaction, western blotting. also examined pathology hematoxylin eosin (HE) safranin O-fast green staining. Finally, we gut rat feces 16 S rRNA gene sequencing.We found that expression MMP-3, NLRP3 Caspase-1 increased group In contrast, II downregulated. Additionally, severely damaged group, disordered cell arrangement uneven coloration. reversed effects modeling on these factors alleviated cartilage damage. addition, diversity microbial abundance treated IDD.Our findings suggest positive effect maintaining cellular stability alleviating histopathological It affects IDD. Therefore, may serve as promising target amelioration

Language: Английский

Citations

17
HIF-2α/TFR1 mediated iron homeostasis disruption aggravates cartilage endplate degeneration through ferroptotic damage and mtDNA release: A new mechanism of intervertebral disc degeneration DOI Creative Commons
Xingzhi Jing, Wenchao Wang,

Xining He

et al.

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 46, P. 65 - 78

Published: May 1, 2024

Iron overload is a prevalent condition in the elderly, often associated with various degenerative diseases, including intervertebral disc degeneration (IDD). Nevertheless, mechanisms responsible for iron ion accumulation tissues and mechanism that regulate homeostasis remain unclear. Transferrin receptor-1 (TFR1) serves as primary cellular gate, playing pivotal role controlling intracellular levels, however its involvement IDD pathogenesis underlying remains obscure. Firstly, mice model was established to determine metabolism proteins changes during progression. Then CEP chondrocytes were isolated treated TBHP or pro-inflammatory cytokines mimic pathological environment, western blotting, immunofluorescence assay tissue staining employed explore mechanisms. Lastly, TfR1 siRNA Feristatin II of examined using micro-CT immunohistochemical analysis. We found characterized by oxidative stress cytokines, could enhance influx upregulating TFR1 expression HIF-2α dependent manner. Excessive not only induces ferroptosis exacerbates stress, but also triggers innate immune response mediated c-GAS/STING, promoting mitochondrial damage release mtDNA. The inhibition STING through reduction mtDNA replication ethidium bromide alleviated induced overload. Our study systemically explored mechanisms, implying targeting maintain balanced offer promising therapeutic approach management. demonstrated close link between dysfunction IDD, indicated may be novel strategy IDD.

Language: Английский

Citations

7