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Research Paper|Volume 13, Issue 13|pp 17227—17236

miR-let-7c-5p and miR-149-5p inhibit proinflammatory cytokine production in osteoarthritis and rheumatoid arthritis synovial fibroblasts

Yat-Yin Law1,2, Wei-Fang Lee3, Chin-Jung Hsu4,5, Yen-You Lin6, Chun-Hao Tsai5,7, Chien-Chung Huang6,8, Min-Huan Wu9,10, Chih-Hsin Tang6,11,12, Ju-Fang Liu13
  • 1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 2Department of Orthopedics, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 3School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
  • 4School of Chinese Medicine, China Medical University, Taichung, Taiwan
  • 5Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
  • 6School of Medicine, China Medical University, Taichung, Taiwan
  • 7Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
  • 8Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
  • 9Bachelor of Science in Senior Wellness and Sports Science, Tunghai University, Taichung, Taiwan
  • 10Tunghai University Sports Recreation and Health Management Degree Program, Tunghai University, Taichung, Taiwan
  • 11Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
  • 12Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
  • 13School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
Received: March 2, 2021Accepted: June 4, 2021Published: July 1, 2021
https://doi.org/10.18632/aging.203201

Copyright: © 2021 Law et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common types of arthritis. Both are characterized by the infiltration of a number of proinflammatory cytokines into the joint microenvironment. miRNAs play critical roles in the disease processes of arthritic disorders. However, little is known about the effects of miRNAs on critical inflammatory cytokine production with OA and RA progression. Here, we found higher levels of proinflammatory cytokines including interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in human OA and RA synovial fibroblasts (SFs) compared with normal SFs. Searches of open-source microRNA (miRNA) software determined that miR-let-7c-5p and miR-149-5p interfere with IL-1β, IL-6 and TNF-α transcription; levels of all three proinflammatory cytokines were lower in human OA and RA patients compared with normal controls. Anti-inflammatory agents dexamethasone, celecoxib and indomethacin reduced proinflammatory cytokine production by promoting the expression of miR-let-7c-5p and miR-149-5p. Similarly, ibuprofen and methotrexate also enhanced miR-let-7c-5p and miR-149-5p expression in human SFs. The evidence suggests that increasing miR-let-7c-5p and miR-149-5p expression is a novel strategy for OA and RA.