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

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
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
Mechanisms of inhibition of nucleus pulposus cells pyroptosis through SDF1/CXCR4-NFkB-NLRP3 axis in the treatment of intervertebral disc degeneration by Duhuo Jisheng Decoction DOI Creative Commons

Daru Guo,

Kang Cheng,

Chao Song

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 124, P. 110844 - 110844

Published: Aug. 28, 2023

Intervertebral disc degeneration (IVDD) is one of the leading causes lower back pain and most common health problem in world. Inflammasomes, which mainly caused by NLRP3, mediated nucleus pulposus pyroptosis has been discovered to be strongly related IVDD. In addition, Duhuo Jisheng Decoction (DHJSD) anti-inflammatory regulatory effects on NLRP3 inflammasome, but molecular mechanism whether DHJSD can regulate through treat IVDD unclear. this study, we used a bioinformatics way discover regulation IVDD, validated our predictions vitro vivo experiments. Through bioinformatics, found that GSDMD, IL-1βand other hub proteins were highly expressed SD rats, network pharmacology may control cellular senescence, apoptosis, order Additional findings demonstrated could successfully brought imaging histomorphological analysis. Western blot showed key protein pyroptosis, was elevated rat degenerated tissue lipopolysaccharide-treated Nucleus Cells (NPCs), intervention effective reducing LPS-induced inflammatory responses further suppressing expression improve The specific inhibits NPCs via SDF-1/CXCR4-NF-kB-NLRP3 axis. conclusion, revealed intrinsic its value for treatment.

Language: Английский

Citations

19
The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation DOI
Nan Wang, Shuang Chen,

Yimin Xie

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 127, P. 155480 - 155480

Published: Feb. 24, 2024

Language: Английский

Citations

8
Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration DOI Creative Commons

Ye-Hui Wang,

Yi Zhou, Xiang Gao

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(1), P. e0290925 - e0290925

Published: Jan. 2, 2024

Background Articular cartilage and matrix degradation are key pathological changes occurring in the early stage of knee osteoarthritis (KOA). However, currently, there limited strategies for prevention treatment KOA. Duhuo Jisheng Decoction (DHJSD) is a formula quoted Bei Ji Qian jin Yao Fang , which was compiled by Sun Simiao Tang Dynasty China. As complementary therapy, it widely used to treat early-stage KOA China; however, its mechanism has not been completely elucidated. Objective This study investigated potential role DHJSD preventing underlying mechanism. Methods A rat model established via Hulth method. Subsequently, 25 rats were randomized into sham (saline), control high-DHJSD (1.9g/mL DHJSD), medium-DHJSD (1.2g/mL low-DHJSD groups (0.6g/mL DHJSD). After 4 weeks treatment, all sacrificed severity degeneration evaluated series histological methods. The autophagosome observed using transmission electron microscopy, related functional proteins detected western blotting real-time polymerase chain reaction. Next, improves further clarified vitro gene silencing technology combined with experiments. levels PTEN, Akt, p-Akt, mTOR, p-mTOR, as well marker autophagy apoptosis determined. Zinc chondrocytes determined inductively coupled plasma mass spectrometry. Results Histopathological staining revealed that had protective effect on cartilage. increased synthesis expression LC3 Beclin-1 chondrocytes. Moreover, reduced phosphorylation Akt mTOR zinc, MMP-13, Bax, Bcl-2. Following PTEN silencing, this DHJSD-mediated reduction Bcl-2, zinc decreased; addition, increase decreased. Conclusion inhibits Akt/mTOR signaling pathway targeting promote chondrocytes, may help reduce MMP-13 production regulating

Language: Английский

Citations

5
Analysis of Key Differential Metabolites in Intervertebral Disc Degeneration Based on Untargeted Metabolomics DOI Creative Commons

Daqian Zhou,

Xingrui Zhang,

Jiale Lv

et al.

JOR Spine, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 8, 2025

ABSTRACT Background Intervertebral disc degeneration disease (IVDD) is a prevalent orthopedic condition that causes chronic lower back pain, imposing substantial economic burden on patients and society. Despite its high incidence, the pathophysiological mechanisms of IVDD remain incompletely understood. Objective This study aimed to identify metabolomic alterations in explore key metabolic pathways metabolites involved pathogenesis. Methods Serum samples from 20 healthy controls were analyzed using ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC–MS). The identified mapped Kyoto Encyclopedia Genes Genomes (KEGG) database. Results Significant observed such as 2‐methyl‐1,3‐cyclohexadiene, stearoyl sphingomyelin, methylcysteine, L‐methionine, cis, cis‐muconic acid. These including glycine, serine, threonine metabolism, cyanoamino acid citrate cycle (TCA cycle). Conclusion provide insights into pathogenesis suggest potential therapeutic targets for future investigation.

Language: Английский

Citations

0
Causal Relationship Between Mitochondrial DNA Copy Number and Intervertebral Disc Degeneration: A Bidirectional 2-Sample Mendelian Randomization Study DOI Creative Commons

Chengjie Ma,

Junhua Fang, Rui Xu

et al.

World Neurosurgery, Journal Year: 2025, Volume and Issue: 196, P. 123732 - 123732

Published: March 13, 2025

Language: Английский

Citations

0
Ferroptosis: A New Direction in the Treatment of Intervertebral Disc Degeneration DOI

Yongliang Mei,

Liquan Wang,

Ting Chen

et al.

Cell Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 5, 2024

Language: Английский

Citations

1
Cell Membrane-Camouflaged Biomimetic Magnetic Fluorescent Nanoparticles with Enhanced Stability for High-Performance Lead Drug Discovery DOI
Jiang Xu, Yi Qin, Haiwei Wang

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 15, 2024

Biomimetic nanoengineering empowers nanoparticles with enhanced biointerfacial capabilities by directly utilizing cell membranes (CMs) of natural origin. This top-down technique provides a powerful tool for the screening potentially active compounds in complex matrices. Herein, cartilaginous end plate (CEP) membrane biomimetic Nile red (NR)-loaded zeolitic imidazolate frameworks-8 (ZIF-8) modified magnetic graphene oxide (CEP/MGO-ZIF-8-NR) nanocomposites stability were accurately prepared chemical bonding and used as drug discovery platform specific identification effective extraction leads anti-intervertebral disc degeneration (IDD) Yaobitong capsules (YBTCs). The constructed CEP/MGO-ZIF-8-NR exhibited excellent properties, fluorescence stability. In addition, binding experiments showed that possessed higher adsorption capacity, faster rate, superior selectivity compared uncoated MGO-ZIF-8-NR. Ultimately, four potential bioactive molecules, including ginsenoside Ro, Rg1, astringin, chikusetsusaponin V methyl ester, successfully screened identified vitro from YBTC. results CCK-8 assay BrdU ELISA kit promoted CEP proliferation concentration-dependent manner. Cellular distribution revealed could rapidly escape lysosomes into cytoplasm. And pharmacological activity these was further confirmed real-time cytomorphological imaging cells confocal laser scanning microscopy (CLSM). Overall, this surface engineering strategy endows bioaffinity sample pretreatment materials tremendous versatility, improves efficiency, broadens horizons methodologies lead discovery.

Language: Английский

Citations

1
Analysis of the role of PANoptosis in intervertebral disk degeneration via integrated bioinformatics analysis and experimental validation DOI

Daqian Zhou,

Jiale Lv,

Yongliang Mei

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 143, P. 113528 - 113528

Published: Nov. 17, 2024

Language: Английский

Citations

1