Abstract
MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arthritis, Rheumatoid / genetics*
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Arthritis, Rheumatoid / pathology
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Arthritis, Rheumatoid / therapy
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CRISPR-Cas Systems / genetics*
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Gene Expression Regulation, Developmental
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Gene Knockout Techniques
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Genome
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Humans
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Inositol Polyphosphate 5-Phosphatases
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Mice
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MicroRNAs / genetics*
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Osteoclasts / metabolism
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Osteogenesis / genetics
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
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Phosphoric Monoester Hydrolases / biosynthesis
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Phosphoric Monoester Hydrolases / genetics
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RANK Ligand / biosynthesis
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RANK Ligand / genetics
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RNA Editing / genetics*
Substances
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MicroRNAs
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RANK Ligand
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Tnfsf11 protein, mouse
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Phosphoric Monoester Hydrolases
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Inositol Polyphosphate 5-Phosphatases
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INPP5D protein, human
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Inpp5d protein, mouse
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases