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“This study provides novel insights into the pathogenesis of OA and suggests a potential therapeutic target in OA treatment.”
BUFFALO, NY- February 13, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 16, Issue 2, entitled, “IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts.”
The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear.
In this new study, researchers Kun-Tsan Lee, Chih-Yang Lin, Shan-Chi Liu, Xiu-Yuan He, Chun-Hao Tsai, Chih-Yuan Ko, Yuan-Hsin Tsai, Chia-Chia Chao, Po-Chun Chen, and Chih-Hsin Tang from National Chung-Hsing University, Taichung Veterans General Hospital, Shin-Kong Wu Ho-Su Memorial Hospital, Mackay Medical College, China Medical University, Show-Chwan Memorial Hospital, Fu-Jen Catholic University, National Taiwan Normal University, Asia University, and China Medical University Hsinchu Hospital used synovial tissues collected from healthy donors and OA patients to detect the expression level of IL-18 by immunohistochemistry stain.
“Elucidation of the molecular mechanisms and main factors involved in OA pathogenesis may help with the development of novel therapeutic targets that relieve OA pain or prevent the disease from progressing.”
The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR.
This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17.
“This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.”
Read the full paper: DOI: https://doi.org/10.18632/aging.205462
Corresponding Authors: Po-Chun Chen, Chih-Hsin Tang
Corresponding Emails: pcchen@ntnu.edu.tw, chtang@mail.cmu.edu.tw
Keywords: osteoarthritis, IL-17, IL-18
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About Aging:
Launched in 2009, Aging publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.
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