scholarly journals Sinapic Acid Inhibits IL-1β-Induced Apoptosis and Catabolism in Nucleus Pulposus Cells and Ameliorates Intervertebral Disk Degeneration

2020 ◽  
Vol Volume 13 ◽  
pp. 883-895
Author(s):  
Jin-Feng Huang ◽  
Xuan-Qi Zheng ◽  
Jia-Liang Lin ◽  
Kai Zhang ◽  
Hai-Jun Tian ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Sinapic Acid ◽  
Intervertebral Disk ◽  
Nucleus Pulposus Cells ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Induced Apoptosis

scholarly journals Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qi Sun ◽  
Xin-Yu Nan ◽  
Fa-Ming Tian ◽  
Fang Liu ◽  
Shao-Hua Ping ◽  
...  
Keyword(s):  
Nucleus Pulposus ◽  
Lumbar Fusion ◽  
B Cell Lymphoma ◽  
Intervertebral Disk ◽  
Ovariectomized Rats ◽  
Tunel Staining ◽  
Mineral Density ◽  
Vertebral Osteoporosis ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration

Abstract Background Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis. Methods An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated. Results RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group. Conclusions RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.

scholarly journals CRISPR/dCas9-Mediated Parkin Inhibition Impairs Mitophagy and Aggravates Apoptosis of Rat Nucleus Pulposus Cells Under Oxidative Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Tao Lan ◽  
Yu-chen Zheng ◽  
Ning-dao Li ◽  
Xiao-sheng Chen ◽  
Zhe Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
Pathological Condition ◽  
Protective Role ◽  
Intervertebral Disk ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Regulation Mechanism ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis ◽  
Design And Methods

ObjectiveThe aim of this study is to explore the role of Parkin in intervertebral disk degeneration (IDD) and its mitophagy regulation mechanism.Study design and methodsRat nucleus pulposus (NP) cells were stimulated with hydrogen peroxide (H2O2) to a mimic pathological condition. Apoptosis and mitophagy were assessed by Western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and immunofluorescence staining. The CRISPR–dCas9–KRAB system was used to silence the expression of Parkin.ResultIn this study, we found that Parkin was downregulated in rat NP cells under oxidative stress. In addition, treatment with H2O2 resulted in mitochondrial dysfunction, autophagy inhibition, and a significant increase in the rate of apoptosis of NP cells. Meanwhile, mitophagy inhibition enhanced H2O2-induced apoptosis. Furthermore, repression of Parkin significantly attenuated mitophagy and exacerbated apoptosis.ConclusionThese results suggested that Parkin may play a protective role in alleviating the apoptosis of NP cells via mitophagy, and that targeting Parkin may provide a promising therapeutic strategy for the prevention of IDD.

scholarly journals Impact of NF-κB pathway on the intervertebral disc inflammation and degeneration induced by over‐mechanical stretching stress

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Hui Xu ◽  
Guobao Qi ◽  
Kunpeng Li ◽  
Keshi Yang ◽  
Dawei Luo ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Cell Model ◽  
Intervertebral Disk ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Tnf Α ◽  
Collagen Ii ◽  
Induced Apoptosis ◽  
Mechanical Stretching

Abstract Background Intervertebral disk degeneration (IVDD) contributes to low back pain. Increased cell apoptosis and inflammation, decreased extracellular matrix are associated with IVDD. Nuclear factor-kappa B (NF-κB) signaling pathway and inflammatory cytokines are implicated in the pathophysiology of IVDD. Methods In present study, we established a mechanical stretching stress-stimulated nucleus pulposus (NP) cell model. We knocked down NF-κB p65 by siRNA transfection to inhibit NF-κB and evaluated the effects of NF-κB inhibition on intervertebral disk degeneration. We applied the mechanical stretching stress on NP cells and inhibited NF-κB by siRNA, then evaluated the expression of inflammatory cytokines, matrix metalloproteinase (MMP), aggrecan, collagen II, and monitored viability and apoptosis of NP cells. Results Mechanical stretching stress induced the expression of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while inhibited the production of aggrecan and collagen II in NP cells. Mechanical stretching stress decreased the cell viability and induced apoptosis in NP cells. Inhibition of NF-κB by siRNA suppressed the production of TNF-α, IL-1β, NF-κB, MMP-3 and MMP-13, while upregulated the expression of aggrecan and collagen II in NP cells. Conclusions Inhibition of NF-κB by knocking down p65 suppressed over-mechanical stretching stress-induced cell apoptosis and promoted viability in NP cell. Inhibition of NF-κB suppressed inflammation and degeneration of NP cells in IVDD.

scholarly journals Circ_0040039 May Aggravate Intervertebral Disk Degeneration by Regulating the MiR-874-3p-ESR1 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yongjin Li ◽  
Xuke Wang ◽  
Haiwei Xu ◽  
Guowang Li ◽  
Zhenxin Huo ◽  
...  
Keyword(s):  
Interaction Network ◽  
Intervertebral Disk ◽  
Circular Rnas ◽  
Ppi Network ◽  
Nucleus Pulposus Cells ◽  
Protein Protein Interaction ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Esr1 Expression ◽  
Functional Alteration

The functional alteration of nucleus pulposus cells (NPCs) exerts a crucial role in the occurrence and progression of intervertebral disk degeneration (IDD). Circular RNAs and microRNAs (miRs) are critical regulators of NPC metabolic processes such as growth and apoptosis. In this study, bioinformatics tools, encompassing Gene Ontology pathway and Venn diagrams analysis, and protein–protein interaction (PPI) network construction were used to identify functional molecules related to IDD. PPI network unveiled that ESR1 was one of the most critical genes in IDD. Then, a key IDD-related circ_0040039-miR-874-3p-ESR1 interaction network was predicted and constructed. Circ_0040039 promoted miR-874-3p and repressed ESR1 expression, and miR-874-3p repressed ESR1 expression in NPCs, suggesting ESR1 might be a direct target of miR-874-3p. Functionally, circ_0040039 could enhance NPC apoptosis and inhibit NPC growth, revealing that circ_0040039 might aggravate IDD by stabilizing miR-874-3p and further upregulating the miR-874-3p-ESR1 pathway. This signaling pathway might provide a novel therapeutic strategy and targets for the diagnosis and therapy of IDD-related diseases.

scholarly journals Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Chunxu Li ◽  
Qiushi Bai ◽  
Yuxiao Lai ◽  
Jingjing Tian ◽  
Jiahao Li ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Nucleus Pulposus ◽  
Cell Transplantation ◽  
Annulus Fibrosus ◽  
Functional Polymers ◽  
Intervertebral Disk ◽  
Fusion Surgery ◽  
Intervertebral Disk Degeneration ◽  
Disk Degeneration ◽  
Intervertebral Disks

Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.

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