ArticleBioengineering & translational medicine2023
Exosomes from M2c macrophages alleviate intervertebral disc degeneration by promoting synthesis of the extracellular matrix via MiR-124/CILP/TGF-β.
Article in Bioengineering & translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Global trends and hotspots of macrophage-related research in intervertebral disc degeneration from 2005 to 2025: a bibliometric and visualized analysis.Frontiers in immunology · 2026Pooled it
- Gut-Intervertebral Disc Axis: Gut Microbiome-Driven Immune-Metabolic Imbalance and Intervertebral Disc Degeneration.Journal of cellular physiology · 2026Review
- 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
- Cartilage intermediate layer protein inhibits ligamentum flavum hypertrophy mediated by TGF-β1/SMAD3/SERPINE2 signaling pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Interleukin-Mediated Macrophage Polarization in Allergic Rhinitis Inflammation: A Systematic Review.Journal of inflammation research · 2026Review
- Spatiotemporal Double-Edged Sword of Macrophages: Temporal Regulation of Neuroinflammation and Neurorepair in Ischemic Stroke.Journal of immunology research · 2026Review
- Regenerative Potential of Extracellular Vesicles on Intervertebral Disc Degeneration: What is the EV-idence?JOR spine · 2025Review
- Review
- From molecular regulation to tissue repair: hydrogels in the fight against intervertebral disc degeneration.Annals of medicine · 2025Review
- Advanced hydrogel therapeutics for intervertebral disc degeneration: Engineering structural-functional properties in natural and synthetic biomaterials.Bioengineering & translational medicine · 2025Review
- Polarized Macrophages and Their Exosomes: Implications for Autoimmune and Immune-Mediated Diseases.Biology · 2025Review
- Macrophage Efferocytosis as a Therapeutic Strategy in Intervertebral Disc Degeneration.Cell proliferation · 2025Review
- Regenerative strategies for intervertebral disc degeneration.Journal of orthopaedic translation · 2025Review
- Mechanisms and Therapeutic Strategies of Macrophage Polarization in Intervertebral Disc Degeneration.JOR spine · 2025Review
- GM@mTG-V microspheres promote NP regeneration by reconstructing IVD biomechanics and inflammatory microenvironment.Materials today. Bio · 2025Article
- Role of M2 macrophage-derived exosomes in cancer drug resistance via noncoding RNAs.Discover oncology · 2025Review
- Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms.Stem cell research & therapy · 2025Review
- Mechanism of microRNA-124-3p targeting calpain-1 to affect the function of intervertebral disc nucleus pulposus cells.Cytotechnology · 2025Article
- FSTL1 accelerates nucleus pulposus-derived mesenchymal stem cell apoptosis in intervertebral disc degeneration by activating TGF-β-mediated Smad2/3 phosphorylation.Journal of translational medicine · 2025Article
- Role of macrophage in intervertebral disc degeneration.Bone research · 2025Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immuno-inflammation is highly associated with anabolic and catabolic dysregulation of the extracellular matrix (ECM) in the nucleus pulposus (NP), which dramatically propels intervertebral disc degeneration (IVDD). With the characteristics of tissue remodeling and regeneration, M2c macrophages have attracted great attention in research on immune modulation that rebuilds degenerated tissues. Therefore, we first demonstrated the facilitating effects of M2c macrophages on ECM anabolism of the NP in vitro. We subsequently found that exosomes from M2c macrophages (M2c-Exoss) mediated their metabolic rebalancing effects on the ECM. To determine whether M2c-Exoss served as positive agents protecting the ECM in IVDD, we constructed an M2c-Exos-loaded hyaluronic acid hydrogel (M2c-Exos@HA hydrogel) and implanted it into the degenerated caudal disc of rats. The results of MRI and histological staining indicated that the M2c-Exos@HA hydrogel alleviated IVDD in vivo in the long term. To elucidate the underlying molecular mechanism, we performed 4D label-free proteomics to screen dysregulated proteins in NPs treated with M2c-Exoss. Cartilage intermediate layer protein (CILP) was the key protein responsible for the rebalancing effects of M2c-Exoss on ECM metabolism in the NP. With prediction and verification using luciferase assays and rescue experiments, miR-124-3p was identified as the upstream regulator in M2c-Exoss that regulated CILP and consequently enhanced the activity of the TGF-β/smad3 pathway. In conclusion, we demonstrated ameliorating effects of M2c-Exoss on the imbalance of ECM metabolism in IVDD via the miR-124/CILP/TGF-β regulatory axis, which provides a promising theoretical basis for the application of M2c macrophages and their exosomes in the treatment of IVDD.
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Registered trials
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.