ArticleArthritis research & therapy2018
Osteogenic differentiation of fibroblast-like synovial cells in rheumatoid arthritis is induced by microRNA-218 through a ROBO/Slit pathway.
Article in Arthritis research & therapy, 2018. 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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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- The clinical role of lncRNA PRKG1-AS1 in lumbar disc degeneration and its mechanism in regulating inflammation and ferroptosis via miR-218-5p.Journal of orthopaedic surgery and research · 2026Article
- Low-input deep learning platform for citrullinated peptide identification, autoantigen discovery and rheumatoid arthritis treatment stratification.Nature biomedical engineering · 2026Article
- microRNAs as Biomarkers and Therapeutic Targets in Rheumatoid Arthritis.International journal of molecular sciences · 2025Review
- A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis.Nature communications · 2025Article
- Differential expression of plasma extracellular vesicle miRNAs as biomarkers for distinguishing psoriatic arthritis from psoriasis.Chinese medical journal · 2025Article
- The Potential Application of Exosomes as Therapeutic Agents, Carriers, and Biomarkers in Skin Diseases.International journal of nanomedicine · 2025Review
- Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review.Frontiers in immunology · 2024Review
- MicroRNAs as Key Regulators in RA and SLE: Insights into Biological Functions.Current pharmaceutical design · 2024Review
- Role of miRNAs in Rheumatoid Arthritis Therapy.Cells · 2023Review
- Comprehensive overview of microRNA function in rheumatoid arthritis.Bone research · 2023Review
- Pulsed Electromagnetic Field Therapy and Direct Current Electric Field Modulation Promote the Migration of Fibroblast-like Synoviocytes to Accelerate Cartilage Repair In Vitro.Applied sciences (Basel, Switzerland) · 2022Article
- Review
- The monocyte-to-osteoclast transition in rheumatoid arthritis: Recent findings.Frontiers in immunology · 2022Review
- MicroRNA-Mediated Epigenetic Regulation of Rheumatoid Arthritis Susceptibility and Pathogenesis.Frontiers in immunology · 2022Review
- Identification of Tissue-Specific Expressed Hub Genes and Potential Drugs in Rheumatoid Arthritis Using Bioinformatics Analysis.Frontiers in genetics · 2022Article
- Review
- The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications.International journal of molecular sciences · 2021Review
- miRNA-218-5p increases cell sensitivity by inhibiting PRKDC activity in radiation-resistant lung carcinoma cells.Thoracic cancer · 2021Article
- Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2021Article
- Crosstalk between Bone and Nerves within Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFibroblast-like synovial cells (FLS) have multilineage differentiation potential including osteoblasts. We aimed to investigate the role of microRNAs during the osteogenic differentiation of rheumatoid arthritis (RA)-FLS.
methodsRA-FLS were differentiated in osteogenic medium for 21 days. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining and Alizarin Red staining. MicroRNA (miRNA) array analysis was performed to investigate the differentially expressed miRNAs during osteogenic differentiation. Expression of miR-218-5p (miR-218) during the osteogenic differentiation was determined by quantitative real-time PCR. Transfections with an miR-218 precursor and inhibitor were used to confirm the targets of miR-218 and to analyze the ability of miR-218 to induce osteogenic differentiation. Secreted Dickkopf-1 (DKK1) from FLS transfected with miR-218 precursor/inhibitor or roundabout 1 (ROBO1) knockdown FLS established using ROBO1-small interfering RNA (siRNA) were measured by ELISA.
resultsThe miRNA array revealed that 12 miRNAs were upregulated and 24 miRNAs were downregulated after osteogenic differentiation. We observed that the level of miR-218 rose in the early phase of osteogenic differentiation and then decreased. Pro-inflammatory cytokines modified the expression of miR-218. The induction of miR-218 in RA-FLS decreased ROBO1 expression, and promoted osteogenic differentiation. Both the overexpression of miR-218 and the knockdown of ROBO1 in RA-FLS decreased DKK1 secretion.
conclusionWe identified miR-218 as a crucial inducer of the osteogenic differentiation of RA-FLS. MiR-218 modulates the osteogenic differentiation of RA-FLS through the ROBO1/DKK-1 axis. The induction of the osteogenic differentiation of proliferating RA-FLS through the provision of miR-218 into RA-FLS or by boosting the cellular reservoir of miR-218 might thus become a therapeutic strategy for RA.
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