ArticleExperimental & molecular medicine2024
Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway.
Article in Experimental & molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Mass-Spectrometry-Identified Quality Markers of Jingtong Granules Are Predicted to Engage Upregulated Neutrophil Granule Enzymes in Cervical Spondylotic Radiculopathy: An Integrative Machine-Learning and Molecular-Dynamics Study.Rapid communications in mass spectrometry : RCM · 2026Article
- Integrated bioinformatics, single-cell analysis, and experimental validation identify quercetin as a potential therapeutic candidate for intervertebral disc degeneration.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Advances in the study of macrophage polarization in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Apoptotic extracellular vesicles derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by enhancing cell activity and regulating immunity microenvironment.Materials today. Bio · 2026Article
- Exploring the mechanisms underlying quercetin, a key component ofFrontiers in immunology · 2026Article
- From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.Military Medical Research · 2026Review
- Utilising bioinformatics and molecular docking technology to explore the underlying mechanisms of intervertebral disc degeneration with potential therapeutic drugs and formulas.Journal of global health · 2025Article
- What a pain in the back: etiology, diagnosis and future treatment directions for discogenic low back pain.Bone research · 2025Review
- Understanding the Microenvironment of Intervertebral Disc Degeneration: A Comprehensive Review of Pathophysiological Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Human iPSCs Derived MSCs-Secreted Exosomes Modulate Senescent Nucleus Pulposus Cells Induced Macrophage Polarization via Metabolic Reprogramming to Mitigate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Modulating Macrophage-Nucleus Pulposus Cell Crosstalk via Sequential Drug Delivery Attenuates Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- β-Mangostin Attenuates TET2-Mediated DNA Demethylation of Prkcg in the Prevention of Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration.JOR spine · 2025Review
- Degradation of WE43 Magnesium Alloy in Vivo and Its Degradation Products on Macrophages.ACS omega · 2025Article
- Bulk RNA-seq conjoined with ScRNA-seq analysis reveals the molecular characteristics of nucleus pulposus cell ferroptosis in rat aging intervertebral discs.Arthritis research & therapy · 2025Article
- Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.Cancer cell international · 2025Review
- The complex role of regulatory cells in breast cancer: implication for immunopathogenesis and immunotherapy.Breast cancer (Tokyo, Japan) · 2025Review
- Unraveling the bidirectional relationship between muscle inflammation and satellite cells activity: influencing factors and insights.Journal of muscle research and cell motility · 2025Review
- Role of macrophage in intervertebral disc degeneration.Bone research · 2025Review
- MiRNA Let-7i-5p-Contained Small Extracellular Vesicles from Macrophages Induce Nucleus Pulposus Cell Senescence via Targeting LIN28A.International journal of nanomedicine · 2025Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lower back pain (LBP), which is a primary cause of disability, is largely attributed to intervertebral disc degeneration (IDD). Macrophages (MΦs) in degenerated intervertebral discs (IVDs) form a chronic inflammatory microenvironment, but how MΦs are recruited to degenerative segments and transform into a proinflammatory phenotype remains unclear. We evaluated chemokine expression in degenerated nucleus pulposus cells (NPCs) to clarify the role of NPCs in the establishment of an inflammatory microenvironment in IDD and explored the mechanisms. We found that the production of C-C motif chemokine ligand 2 (CCL2) and C-C motif chemokine ligand 7 (CCL7) was significantly increased in NPCs under inflammatory conditions, and blocking CCL2/7 and their receptor, C-C chemokine receptor type 2(CCR2), inhibited the inductive effects of NPCs on MΦ infiltration and proinflammatory polarization. Moreover, activation of the integrated stress response (ISR) was obvious in IDD, and ISR inhibition reduced the production of CCL2/7 in NPCs. Further investigation revealed that activating Transcription Factor 3 (ATF3) responded to ISR activation, and ChIP-qPCR verified the DNA-binding activity of ATF3 on CCL2/7 promoters. In addition, we found that Toll-like receptor 4 (TLR4) inhibition modulated ISR activation, and TLR4 regulated the accumulation of mitochondrial reactive oxygen species (mtROS) and double-stranded RNA (dsRNA). Downregulating the level of mtROS reduced the amount of dsRNA and ISR activation. Deactivating the ISR or blocking CCL2/7 release alleviated inflammation and the progression of IDD in vivo. Moreover, MΦ infiltration and IDD were inhibited in CCR2-knockout mice. In conclusion, this study highlights the critical role of TLR4/mtROS/dsRNA axis-mediated ISR activation in the production of CCL2/7 and the progression of IDD, which provides promising therapeutic strategies for discogenic LBP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.