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MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation
Journal article   Open access   Peer reviewed

MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation

Liu Hong, Thad Sharp, Behnoush Khorsand, Carol Fischer, Steven Eliason, Ali Salem, Adil Akkouch, Kim Brogden and Brad A Amendt
PloS one, Vol.11(8), pp.e0160915-e0160915
2016
DOI: 10.1371/journal.pone.0160915
PMCID: PMC4987006
PMID: 27529418
url
https://doi.org/10.1371/journal.pone.0160915View
Published (Version of record) Open Access

Abstract

MicroRNAs (miRs) regulate inflammation and BMP antagonists, thus they have potential uses as therapeutic reagents. However, the molecular function of miR-200c in modulating proinflammatory and bone metabolic mediators and osteogenic differentiation is not known. After miR-200c was transduced into a human embryonic palatal mesenchyme (HEPM) (a cell line of preosteoblasts), using lentiviral vectors, the resulting miR-200c overexpression increased osteogenic differentiation biomarkers, including osteocalcin (OCN) transcripts and calcium content. miR-200c expression also down-regulated interleukin (IL)-6, IL-8, and chemokine (C-C motif) ligand (CCL)-5 under lipopolysaccharide (LPS) stimulation and increased osteoprotegerin (OPG) in these cells. miR-200c directly regulates the expression of IL-6, IL-8 and CCL-5 transcripts by binding to their 3'UTRs. A plasmid-based miR-200c inhibitor effectively reduces their binding activities. Additionally, miR-200c delivered using polyethylenimine (PEI) nanoparticles effectively inhibits IL-6, IL-8 and CCL-5 in primary human periodontal ligament fibroblasts and increases the biomarkers of osteogenic differentiation in human bone marrow mesenchymal stem cells (MSCs), including calcium content, ALP, and Runx2. These data demonstrate that miR-200c represses IL-6, IL-8 and CCL-5 and improves osteogenic differentiation. miR-200c may potentially be used as an effective means to prevent periodontitis-associated bone loss by arresting inflammation and osteoclastogenesis and enhancing bone regeneration.
Interleukin-8 - genetics Cell Proliferation - genetics Interleukin-6 - genetics Gene Expression Regulation - genetics Humans 3' Untranslated Regions - genetics Cell Differentiation - genetics Periodontal Ligament - cytology Mesenchymal Stromal Cells - cytology Chemokine CCL5 - genetics HEK293 Cells Fibroblasts - cytology MicroRNAs - genetics Osteoblasts - cytology Osteogenesis - genetics

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