Targeting nucleus pulposus cell death in the treatment of intervertebral disc degeneration DOI Creative Commons

Hong Sun,

Jiajie Guo,

Zhilin Xiong

et al.

JOR Spine, Journal Year: 2024, Volume and Issue: 7(4)

Published: Dec. 1, 2024

Abstract Background Intervertebral disc degeneration (IDD) is a progressive age‐related disorder characterized by the reduction in number of nucleus pulposus cells (NPCs) and degradation extracellular matrix (ECM), thereby leading to chronic pain disability. The pathogenesis IDD multifaceted, current therapeutic strategies remain limited. (NP), primarily composed NPCs, proteoglycans, type II collagen, constitutes essential components for maintaining intervertebral (IVD) function spinal motion. disturbed homeostasis NPCs closely associated with IDD. Accumulating evidence increasingly suggests crucial role programmed cell death (PCD) regulating NPCs. Aims This review aimed elucidate various forms PCD their respective roles IDD, investigate diverse targeting treatment. Materials & Methods We collected relevant literature regarding development Subsequently, we comprehensively summarized intricate association between also explored potential application therapy traditional Chinese medicine (TCM) prevention treatment Results Current indicated that was Additionally, targeted pharmaceuticals based on mechanisms could effectively impede loss Conclusion demonstrated may be promising strategy

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
Humanin reduces nucleus pulposus cells ferroptosis to alleviate intervertebral disc degeneration: An in vitro and in vivo study DOI Creative Commons
Daxue Zhu,

Zhaoheng Wang,

Yanhu Li

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 274 - 294

Published: Jan. 1, 2025

Language: Английский

Citations

1
Role of macrophage in intervertebral disc degeneration DOI Creative Commons

Yiming Dou,

Yiming Zhang, Yang Liu

et al.

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

Language: Английский

Citations

1
GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3 DOI Creative Commons
Xiaobo Wang,

Bingyu Wang,

Jiawei Shi

et al.

International Journal of Biological Sciences, Journal Year: 2025, Volume and Issue: 21(3), P. 1174 - 1186

Published: Jan. 13, 2025

This study explored the role of ferroptosis in intervertebral disc degeneration (IVDD), and identified GATA6 as a key regulator this process. A ferroptosis-related gene risk coefficient model was constructed using differential expression analysis GSE70362 dataset. The significant factor IVDD progression. shown to promote nucleus pulposus cells (NPCs) by regulating AKR1C3 through TLR2 pathway. In vitro vivo experiments demonstrated that knockdown reduced ferroptosis, improved cell viability, mitigated extracellular matrix degradation, whereas overexpression exacerbated these processes. Furthermore, found be crucial for GATA6-mediated modulation TLR2-AKR1C3 axis significantly impacted NPCs. These findings suggest targeting its downstream pathway may provide new therapeutic approaches IVDD.

Language: Английский

Citations

1
Spotlight on necroptosis: Role in pathogenesis and therapeutic potential of intervertebral disc degeneration DOI

Rui Ran,

Shun-Bai Zhang,

Yong-Qiang Shi

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 138, P. 112616 - 112616

Published: July 2, 2024

Language: Английский

Citations

5
Circular RNA CircFOXO3 Functions as a Competitive Endogenous RNA for Acid-Sensing Ion Channel Subunit 1 Mediating Oxeiptosis in Nucleus Pulposus DOI Creative Commons
Xi Chen, Ying Song, Guanghui Chen

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(3), P. 678 - 678

Published: March 18, 2024

Oxeiptosis is a reactive oxygen species (ROS)-induced pathway of cell death. The involvement circular RNAs (circRNAs) has been confirmed in the incidence and progression intervertebral disc degeneration (IVDD). However, whether oxeiptosis occurs IVDD how circRNAs regulate still unclear. In this study, we discovered that could be induced nucleus pulposus cells (NPCs), circFOXO3 was significantly upregulated after induction. Transfection using small interfering RNA (siRNA) inhibited NPCs. Mechanistically, acid-sensing ion channel subunit 1 (ASIC1) expression by functioning as molecular sponge for miR-185-3p miR-939-5p. Subsequent rescue experiments validated NPCs via miR-185-3p/miR-939-5p-ASIC1 axis. Further research on ASIC1 functions indicated regulation achieved affecting Calcium (Ca2+) influx mediated ASIC1. A mouse model established, silencing vivo found to inhibit development activation oxeiptosis-related pathway. Overall, one factors contributing mediating oxeiptosis.

Language: Английский

Citations

4
Daphnetin-mediated mitophagy alleviates intervertebral disc degeneration via the Nrf2/PINK1 pathway DOI Creative Commons

Yiting Tu,

Jiaping Ren,

Weiyuan Fang

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Reactive oxygen species (ROS) stress induces NLRP3 inflammasome activation, this, along with extracellular matrix metabolism (ECM) degradation in nucleus pulposus cells (NPCs), plays crucial role the progression IDD. Daphnetin (DAP) biologically active phytochemical extracted from plants Genus Daphne, which possesses various bioactivities, including antioxidant properties. In present study, we demonstrate that DAP significantly attenuates tert-butyl hydroperoxide (TBHP)-induced ECM degradation, oxidative activation NPCs. Furthermore, could facilitate mitophagy to increase removal damaged mitochondria, consequently reducing mitochondrial ROS accumulation alleviating activation. Mechanistically, unveil activates by stimulating Nrf2/PINK1 signaling pathway TBHP-induced vivo experiments further corroborate protective effect against IDD rat model induced puncture. Accordingly, our findings reveal be promising therapeutic candidate for treatment

Language: Английский

Citations

0
1,25(OH)₂D₃ inhibits ferroptosis in nucleus pulposus cells via VDR signaling to mitigate lumbar intervertebral disc degeneration DOI Creative Commons
Qiang Li, Jing Peng, Fan Ding

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 7, 2025

Lumbar intervertebral disc degeneration (LIDD) serves as a principal contributor to low back pain, condition that poses considerable global health and socioeconomic challenges. Recent studies have emphasized the significance of ferroptosis, an iron-dependent mechanism programmed cell death, in nucleus pulposus cells (NPCs). This research examines protective role 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], active metabolite Vitamin D (VD), LIDD through modulation ferroptosis. The results indicate 1,25(OH)₂D₃ significantly inhibits ferroptosis NPCs reduction lipid peroxidation, restoration glutathione levels, enhancement antioxidant defenses. exerts its effects by activating VD receptor (VDR) signaling pathway, which regulates important ferroptosis-associated molecules, including peroxidase 4 (GPX4) solute carrier family 7 member 11 (SLC7A11). findings therapeutic potential alleviating LIDD, presenting new strategy inhibit maintain function.

Language: Английский

Citations

0
Ferroptosis-related exosomal non-coding RNAs: promising targets in pathogenesis and treatment of non-malignant diseases DOI Creative Commons
Yiping Zhang, Jun Xie

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 7, 2024

Ferroptosis, an iron-dependent form of programmed cell death, introduces a novel perspective on cellular demise. This study investigates the regulatory network exosomal non-coding RNAs (ncRNAs), including miRNAs, circRNAs, and lncRNAs, in ferroptosis modulation. The primary goal is to examine pathological roles ferroptosis-related ncRNAs, particularly ischemic reperfusion injuries. research reveals intricate molecular interactions governing interplay between ncRNAs ferroptosis, elucidating their diverse different non-malignant contexts. Attention given impact diseases, cardiac, cerebral, liver, kidney injuries, as well lung, wound, neuronal Beyond theoretical exploration, provides insights into potential therapeutic applications, emphasizing significance mesenchymal stem cells (MSCs)-derived exosomes. Findings underscore pivotal role MSC-derived modulating responses related regulation, introducing cutting-edge dimension. recognition emphasizes importance exosomes crucial mediators with broad implications. Insights unveil promising avenues for targeted interventions, capitalizing providing comprehensive foundation future strategies.

Language: Английский

Citations

3
Research Progress on the Role of Cartilage Endplate in Intervertebral Disc Degeneration DOI

Ma Zhong,

Xin Liu, Mingtao Zhang

et al.

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(7)

Published: Sept. 12, 2024

Low back pain significantly impacts individuals' quality of life, with intervertebral disc degeneration (IDD) being a primary contributor to this condition. Currently, IDD treatment primarily focuses on symptom management and does not achieve definitive cure. The cartilage endplate (CEP), crucial nutrient-supplying tissue the disc, plays pivotal role in degeneration. This review examines mechanisms underlying CEP degeneration, summarizing recent advancements understanding structure function CEP, involvement various signaling pathways, roles stem cells (CESCs) exosomes (Exos) process. aim is provide comprehensive reference for future research CEP. Despite progress IDD, remain incompletely elucidated. Future poses significant challenges, necessitating further investigations elucidate complexities

Language: Английский

Citations

2