miR-204-5p inhibits inflammation of synovial fibroblasts in osteoarthritis by suppressing FOXC1

Background: The paper is aimed at uncovering the mechanism of miR-204-5p in regulating inflammatory responses of human osteoarthritic synovial fibroblasts (SFs). Methods: IL-1 beta-induced osteoarthritic SFs were established as an osteoarthritis (OA) cell model. The osteoarthritic SFs were accordingly transfected with mimics-miR-204-5p, inhibitors-miR-204-5 or FOXC1 siRNA. MTT tested the vitality of osteoarthritic SFs by analyzing the cell optical density. The expressions of miR-204-5p, FOXC1, TNF-alpha, IL-6, PGE2, MMP-1, MMP-13 and COX-2 in osteoarthritic SFs were measured by qRT-PCR, Western blotting and/or ELISA. The binding of miR-204-5p to FOXC1 was verified through luciferase reporter assay. The regulatory effect of miR-204-5p on FOXC1 was also tested in normal SFs. Results: miR-204-5p was under-expressed and FOXC1 was over-expressed in osteoarthritic SFs. The expressions of FOXC1, TNF-alpha, IL-6, PGE2, MMP-1, MMP-13 and COX-2 were up-regulated in IL-1 beta-treated SFs. Up-regulation of miR-204-5p or down-regulation of FOXC1 suppressed the inflammatory responses of osteoarthritic SFs. miR-204-5p negatively regulated FOXC1 by being a sponge in osteoarthritic SFs as well as in normal SFs. Conclusion: miR-204-5p down-regulates FOXC1 to ameliorate inflammation of SFs in OA. (C) 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Automated summary

The study reveals that miR-204-5p ameliorates inflammatory responses of osteoarthritic synovial fibroblasts by down-regulating FOXC1. Results demonstrate that miR-204-5p negatively regulates FOXC1 in both normal SFs and osteoarthritic SFs.