miR-17-5p reduces inflammation and bone erosions in collagen induced arthritis mice and directly targets the JAK-STAT pathway in rheumatoid arthritis fibroblast-like synoviocytes

Arthritis & Rheumatology
Aurélie NajmFrédéric Blanchard

Abstract

Our aims were to study miR expression across rheumatoid arthritis (RA) phenotypes, along with the effects and mechanisms of action of miR-17-5p. A miR array was performed in synovial tissue biopsy from n=3 naïve erosive and non-erosive RA patients. miR-17 lipoplex was delivered intra-articularly in the murine collagen-induced arthritis model. Clinical, histological and structural effects were studied over the course of arthritis. In depth studies of miR-17 mechanism-of-action were performed in primary RA-FLS isolated from synovial tissue. 55 miRNAs including miR-17 were reduced in erosive RA. miR-17 transfection in arthritic paws reduced clinical inflammation from day 2 to 7 (score 2.8 vs 1.9, p=0.03). Synovial B cells, T cells, macrophages and polynuclear neutrophils infiltrates were significantly reduced. Structural damage was also decreased as shown by a reduction in the number of osteoclasts (TRAP surface/total surface 32 vs. 18%, p=0.005) and erosion score by CT analysis (score 2.9 vs 1.7, p=0.023). Pro-inflammatory cytokines of the IL-6 family, and IL-1β expression was also significantly reduced, but not TNF. miR17 directly targeted the 3'-untranslated regions of STAT3 and JAK1. STAT3 and JAK1 mRNA and protein expression ...Continue Reading

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Citations

Dec 18, 2020·Frontiers in Cell and Developmental Biology·Hanxiao ZhaoXiaojuan He
Mar 23, 2021·Frontiers in Immunology·Clare C CunninghamDouglas J Veale
May 1, 2021·Arthritis Research & Therapy·Julien HermanChristelle Darrieutort-Laffite
May 6, 2021·Rheumatology·Francesca Romana SpinelliMassimo Gadina
Jul 2, 2021·Journal of Ethnopharmacology·Yuan WangYan-Xu Chang
Jul 27, 2021·Frontiers in Immunology·Jie HuangChao Liang
Oct 1, 2021·Nature Reviews. Rheumatology·Shabana A AliMohit Kapoor
Oct 31, 2021·International Journal of Experimental Pathology·Qiang LuHao Xu

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