Epigenetic regulation in intervertebral disc degeneration

Li, Gaocai; Zhang, Weifeng; Liang, Huaizhen; Yang, Cao

doi:10.1016/j.molmed.2022.07.007

Cited by 19 publications

(16 citation statements)

References 10 publications

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“…As a connective and compressive forces‐afforded motif, [ 8,9 ] IVD is prone to degeneration. Inflammatory pathways, such as the activation of the Nuclear Factor Kappa B (NF‐ κ B) pathway, [ 10,11 ] the posttranscriptional modification such as N6‐methyladenosine, [ 12,13 ] and reactive oxygen species (ROS, such as hydrogen peroxide, H 2 O 2 ; superoxide anion, O 2 •− ; and hydroxyl radical, •OH) constitute the harsh oxidative stress microenvironment for the degenerative process. [ 14,15 ]…”

Section: Introductionmentioning

confidence: 99%

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

et al. 2023

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Intervertebral disc degeneration (IVDD)‐induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism is partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it is shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress‐induced ferroptosis in nucleus pulposus (NP) cells in vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe2+ to mitigate iron overload, and regulate the expression of iron storage proteins such as ferritin heavy chain (FHC), ferritin, and transferrin receptor (TFR). More importantly, PDA NPs co‐localize with glutathione peroxidase 4 (GPX4) around the mitochondria and suppress ubiquitin‐mediated degradation, which in turn exerts a protective function via the transformation and clearance of phospholipid hydroperoxides. PDA NPs further down‐regulate malondialdehyde (MDA) and lipid peroxide (LPO) production; thus, antagonizing ferroptosis in NP cells. Moreover, PDA NPs effectively rescue puncture‐induced degeneration in vivo by targeting ferroptosis and inhibiting GPX4 ubiquitination, resulting in the upregulation of antioxidant pathways. The findings offer a new tool to explore the underlying mechanisms and a novel treatment strategy for IVDD‐induced LBP.

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Section: Introductionmentioning

confidence: 99%

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

et al. 2023

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“…A global burden of disease study in 2019 showed that low back pain (LBP) was one of the top 10 causes of disability‐adjusted life‐years, especially in the groups for 10–24 years and 25–49 years 1 . Intervertebral disc disease (IVD) and Intervertebral disc degeneration (IDD), as the leading and major cause of LBP, affects more than 90% of people over 50 years of age 2–4 . It is the largest avascular structure in the human body and receives all nutrients from the bone marrow of adjacent vertebral bodies via the only nutrition channel of endplate cartilage (CEP) 5 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3

Li,

Chen,

Meng

et al. 2023

Orthopaedic Surgery

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ObjectiveNowadays, more than 90% of people over 50 years suffer from intervertebral disc degeneration (IDD), but there are exist no ideal drugs. The aim of this study is to identify a new drug for IDD.MethodsAn approved small molecular drug library including 2040 small molecular compounds was used here. We found that taurocholic acid sodium hydrate (NAT) could induce chondrogenesis and osteogenesis in mesenchymal stem cells (MSCs). Then, an in vivo mouse model of IDD was established and the coccygeal discs transcriptome analysis and surface plasmon resonance analysis (SPR) integrated with liquid chromatography–tandem mass spectrometry assay (LC‐MS) were performed in this study to study the therapy effect and target proteins of NAT for IDD. Micro‐CT was used to evaluate the cancellous bone. The expression of osteogenic (OCN, RNX2), chondrogenic (COL2A1, SOX9), and the target related (ERK1/2, p‐ERK1/2) proteins were detected. The alkaline phosphatase staining was performed to estimate osteogenic differentiation. Blood routine and blood biochemistry indexes were analyzed for the safety of NAT.ResultsThe results showed that NAT could induce chondrogenesis and osteogenesis in MSCs. Further experiments confirmed NAT could ameliorate the secondary osteoporosis and delay the development of IDD in mice. Transcriptome analysis identified 128 common genes and eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for NAT. SPR‐LC–MS assay detected 57 target proteins for NAT, including MAPK3 (mitogen‐activated protein kinase 3), also known as ERK1 (extracellular regulated protein kinase 1). Further verification experiment confirmed that NAT significantly reduced the expression of ERK1/2 phosphorylation.ConclusionNAT would induce chondrogenesis and osteogenesis of MSCs, ameliorate the secondary osteoporosis and delay the progression of IDD in mice by targeting MAPK3.Furthermore, MAPK3, especially the phosphorylation of MAPK3, would be a potential therapeutic target for IDD treatment.

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“…[ 3 ] Nonetheless, current clinical therapeutic strategies, known as conservative treatment and surgical intervention, are aimed at symptom relief rather than directly targeting IVDD. [ 4 ] A novel strategy for targeted intervention techniques for low back pain will emerge from further clarification of the molecular mechanism of IVDD.…”

Section: Introductionmentioning

confidence: 99%

Advanced glycation end products induce nucleus pulposus cell apoptosis by upregulating TXNIP via inhibiting glycolysis pathway in intervertebral disc degeneration

Chen,

Sheng,

Sun

et al. 2023

J Biochem & Molecular Tox

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Accumulation of advanced glycation end products (AGEs) causes apoptosis in human nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IVDD). The purpose of this study was to determine the roles of thioredoxin‐interacting protein (TXNIP) in the mechanisms underlying AGE‐induced apoptosis of NPCs. TXNIP was silenced or overexpressed in HNPCs exposed to AGEs. Glycolysis was assessed using extracellular acidification rate (ECAR), ATP level, GLUT1, and GLUT4 measurements. AGEs, TXNIP, GLUT1, and GLUT4 levels in IVDD patients were measured as well. In NPCs, AGEs reduced cell viability, induced apoptosis, inhibited glycolysis, and increased TXNIP expression. Silencing TXNIP compromised the effects of AGEs on cell viability, apoptosis, and glycolysis in NPCs. Furthermore, TXNIP overexpression resulted in decreased cell viability, increased apoptotic cells, and glycolysis suppression. Furthermore, co‐treatment with a glycolysis inhibitor improved TXNIP silencing's suppressive effects on AGE‐induced cell injury in NPCs. In IVDD patients with Pfirrmann Grades II–V, increasing trends in AGEs and TXNIP were observed, while decreasing trends in GLUT1 and GLUT4. AGE levels had positive correlations with TXNIP levels. Both AGE and TXNIP levels correlated negatively with GLUT1 and GLUT4. Our study indicates that TXNIP plays a role in mediating AGE‐induced cell injury through suppressing glycolysis. The accumulation of AGEs, the upregulation of TXNIP, and the downregulation of GLUT1 and GLUT4 are all linked to the progression of IVDD.

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Epigenetic regulation in intervertebral disc degeneration

Cited by 19 publications

References 10 publications

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Discovery of Taurocholic Acid Sodium Hydrate as a Novel Repurposing Drug for Intervertebral Disc Degeneration by Targeting MAPK3

Advanced glycation end products induce nucleus pulposus cell apoptosis by upregulating TXNIP via inhibiting glycolysis pathway in intervertebral disc degeneration

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