title: MicroRNA-200c Represses IL-6, IL-8, and CCL-5 Expression and Enhances Osteogenic Differentiation.
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.
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, the University of Iowa, Iowa City, IA, United States of America.|Center for Craniofacial Anomalies Research, Carver College of Medicine, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Liu
authors.identifier: http://orcid.org/0000-0003-0308-5049
authors.initials: L
authors.lastname: Hong
authors.affiliation: Department of Anatomy and Cell Biology, Carver College of Medicine, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Thad
authors.initials: T
authors.lastname: Sharp
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Behnoush
authors.initials: B
authors.lastname: Khorsand
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Carol
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Center for Craniofacial Anomalies Research, Carver College of Medicine, the University of Iowa, Iowa City, IA, United States of America.|Department of Anatomy and Cell Biology, Carver College of Medicine, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Eliason
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Salem
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Adil
authors.initials: A
authors.lastname: Akkouch
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Kim
authors.initials: K
authors.lastname: Brogden
authors.affiliation: Dows Institute for Dental Research, College of Dentistry, the University of Iowa, Iowa City, IA, United States of America.|Center for Craniofacial Anomalies Research, Carver College of Medicine, the University of Iowa, Iowa City, IA, United States of America.|Department of Anatomy and Cell Biology, Carver College of Medicine, the University of Iowa, Iowa City, IA, United States of America.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Amendt
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D018946:Chemokine CCL5 / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000235:genetics*; D010513:Periodontal Ligament / Q000166:cytology
chemical_list: D020413:3' Untranslated Regions; D018946:Chemokine CCL5; D015850:Interleukin-6; D016209:Interleukin-8; C533896:MIRN200 microRNA, human; D035683:MicroRNAs