ArticleJOR spine2024
In vitro and ex vivo screening of microRNA combinations with enhanced cell penetrating peptides to stimulate intervertebral disc regeneration.
Article in JOR spine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Defining the Human Nucleus Pulposus Microenvironment and Its Impact on Cell Matrix Synthesis and Metabolic Activity.JOR spine · 2026Article
- Restoring disc matrix homeostasis: Dual-miRNA and human platelet lysate as a novel therapeutic strategy.Materials today. Bio · 2026Article
- Comparative Analysis of Dual-miRNA Mediated Stimulation of Nucleus Pulposus and Bone Marrow Derived Stem Cells for Intervertebral Disc Repair.JOR spine · 2026Article
- Influence of the Intervertebral Disc Microenvironment on Matrix Synthesis and Metabolism in Goat Nucleus Pulposus Cells.JOR spine · 2026Article
- Mendelian randomization analysis identifies HLA-A and AP2M1 as genetic biomarkers linked to immune-endocytic crosstalk in intervertebral disc degeneration.Journal of cell communication and signaling · 2026Article
- Trimethylamine-N-oxide promotes fibrotic activation of quiescent valvular interstitial cells via endoplasmic reticulum stress.Scientific reports · 2025Article
- Enhanced localized pressure-mediated non-viral gene delivery.Drug delivery and translational research · 2025Article
- Co-morbid mechanisms of intervertebral disc degeneration and osteoporosis: biomechanical coupling and molecular pathways synergistically driving degenerative lesions.Journal of orthopaedic surgery and research · 2025Review
- In vitro and ex vivo screening of microRNA combinations with enhanced cell penetrating peptides to stimulate intervertebral disc regeneration.JOR spine · 2024Article
- Versatile Cell Penetrating Peptide for Multimodal CRISPR Gene Editing in Primary Stem Cells.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Low back pain (LBP) is predominantly caused by degeneration of the intervertebral disc (IVD) and central nucleus pulposus (NP) region. Conservative treatments fail to restore disc function, motivating the exploration of nucleic acid therapies, such as the use of microRNAs (miRNAs). miRNAs have the potential to modulate expression of discogenic factors, while silencing the catabolic cascade associated with degeneration. To deliver these miRNAs, nonviral cell penetrating peptides (CPPs) are gaining favor given their low immunogenicity and strong targeting ability. Single miRNA therapies have been investigated for IVD repair, however dual miRNA delivery strategies have not been commonly examined and may augment regeneration. Materials and methods: Transfection of four pro-discogenic miRNAs (miRNA mimics:140-5p; 149-5p and inhibitors: 141-3p; 221-3p) and dual delivery of six miRNA pairings was performed using two CPPs, RALA and GET peptide (FLR), in primary rat NP monolayer culture, and in an ex vivo organ culture model of rat caudal discs. Protein expression of discogenic (aggrecan, collagen type II, and SOX9) and catabolic markers (ADAMTS5 and MMP13) were assessed. Results: Monolayer investigations signified enhanced discogenic marker expression following dual miRNA delivery, signifying a synergistic effect when compared to single miRNA transfection. Utilization of an appropriate model was emphasized in our ex vivo organ culture experiment, revealing the establishment of a regenerative microenvironment characterized by reduced catabolic enzyme activity and enhanced matrix deposition, particularly following concurrent delivery of FLR-miRNA-149-5p mimic and miRNA-221-3p inhibitor. Bioinformatics analysis of miRNA-149-5p mimic and miRNA-221-3p inhibitor identified distinct targets, pathways, and interactions, suggesting a mode of action for this amplified response. Conclusion: Our findings suggest the potential of FLR-miRNA-149-5p + miRNA-221-3p inhibitor to create an anti-catabolic niche within the disc to foster regeneration in moderate cases of disc degeneration, which could be utilized in further studies with the overarching aim of developing treatments for LBP.
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