MicroRNA-9 ameliorates destructive arthritis through down-regulation of NF-κB1-RANKL pathway in fibroblast-like synoviocytes.

Abstract

We investigated the effect of miR-9 on fibroblast-like synoviocytes (FLS) from RA patients and animal arthritis model. The binding of miR-9 to NF-κB1 3'UTR was analyzed by luciferase reporter assay and immunoprecipitation. ChIP assay and luciferase promoter assay were performed to identify the binding of NF-κB1 to RANKL promoter and its activity. FLS were treated with miR-9/anti-miR-9 to evaluate cell proliferation and the expression of RANKL. Therapeutic effect of intra-articular miR-9 was evaluated in type-II collagen-induced arthritis in rats. miR-9 bound to the 3'-UTR of NF-κB1 and downregulated NF-κB1. NF-κB1 bound to RANKL promoter and increased the promoter activity of RANKL. RANKL was downregulated by miR-9. Proliferation of FLS was increased by miR-9 inhibitor. miR-9 dampened experimental arthritis by lowering inflammatory state, reducing RANKL and osteoclasts formation. Our findings revealed miR-9-NF-κB1-RANKL pathway in RA-FLS, further, miR-9 ameliorated inflammatory arthritis in vivo which propose therapeutic implications of miR- 9 in RA.

• Authors: Wen Shi Lee, Shinsuke Yasuda, Michihiro Kono, Yuki Kudo, Sanae Shimamura, Michihito Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Tomohiro Shimizu, Tomohiro Onodera, Norimasa Iwasaki, Tatsuya Atsumi
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 212 Pg. 108348 (03 2020) ISSN: 1521-7035 [Electronic] United States
• PMID: 31978557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• MIRN9 microRNA, rat
• MIRN92 microRNA, human
• MicroRNAs
• NF-kappa B p50 Subunit
• RANK Ligand

Topics

• Aged
• Aged, 80 and over
• Animals
• Arthritis, Experimental (genetics, metabolism, pathology)
• Arthritis, Rheumatoid (genetics, metabolism)
• Down-Regulation
• Female
• Fibroblasts (metabolism)
• Gene Expression Regulation
• Humans
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• NF-kappa B p50 Subunit (genetics, metabolism)
• Osteoarthritis, Knee (genetics, metabolism)
• RANK Ligand (genetics, metabolism)
• Rats
• Synoviocytes (metabolism)
• Transfection