Research Paper|Volume 13, Issue 18|pp 22490—22501

Nesfatin-1 facilitates IL-1β production in osteoarthritis synovial fibroblasts by suppressing miR-204-5p synthesis through the AP-1 and NF-κB pathways

Kun-Tsan Lee^1,², Bo-Cheng Chen³, Shan-Chi Liu⁴, Yen-You Lin³, Chun-Hao Tsai^5,⁶, Chih-Yuan Ko⁶, Chih-Hsin Tang^3,^7,⁸, Kwong-Chung Tung¹

¹Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan
²Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
³School of Medicine, China Medical University, Taichung, Taiwan
⁴Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan
⁵Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
⁶Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
⁷Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
⁸Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan

Received: July 7, 2021Accepted: September 7, 2021Published: September 24, 2021

https://doi.org/10.18632/aging.203559

Copyright: © 2021 Lee 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

The progression of osteoarthritis (OA) is mediated by adipokines, one of which is nesfatin-1, which is responsible for the production of inflammatory cytokines. However, how this molecule may affect the synthesis of the proinflammatory cytokine interleukin 1 beta (IL-1β) in OA is unclear. Our analyses of records from the Gene Expression Omnibus (GEO) dataset and clinical specimens of synovial tissue revealed higher levels of nesfatin-1 and IL-1β in OA samples compared with normal healthy tissue. We found that nesfatin-1 facilitates IL-1β synthesis in human OA synovial fibroblasts (OASFs) and suppresses the generation of micro-RNA (miR)-204-5p, as the miR-204-5p levels in OA patients were lower than those in healthy controls. Nesfatin-1-induced stimulation of IL-1β in human OASFs occurred via the suppression of miR-204-5p synthesis by the PI3K, Akt, AP-1 and NF-κB pathways. We suggest that nesfatin-1 is worth targeting in OA treatment.