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Research Paper|Volume 16, Issue 9|pp 7915—7927

IL21 inhibits miR-361-5p to promote MAP3K9 and further aggravate the progression of shoulder arthritis

Kangning Hao1, Pengchao Lin1, Jing Li2, Jie Hu3, Jiangyong Wang1, Fei Li1
  • 1Department of Orthopedic Surgery, The Third Hospital of Shijiazhuang, Shijiazhuang 050011, Hebei, P.R. China
  • 2Department of Nursing, Hebei Province Eighth People’s Hospital, Shijiazhuang 050011, Hebei, P.R. China
  • 3Department of Radiology, The Third Hospital of Shijiazhuang, Shijiazhuang 050011, Hebei, P.R. China
Received: July 6, 2023Accepted: March 13, 2024Published: May 7, 2024
https://doi.org/10.18632/aging.205793

Copyright: © 2024 Hao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Abstract: Objective: This research aimed to explore IL-21/miR-361-5p/MAP3K9 expression in shoulder arthritis and identify its regulatory pathways.

Methods: We established a rat shoulder arthritis model, then quantified IL21 and miR-361-5p in synovial fluid using ELISA and monitored the arthritis development. Additionally, IL21’s effect on miR-361-5p levels in cultured human chondrocytes (HC-a) was assessed. Chondrocyte cell cycle status and apoptosis were measured via flow cytometry. Interactions between miR-361-5p and MAP3K9 were confirmed through dual-luciferase reporting and bioinformatic scrutiny. Protein levels of MAP3K9, p-ERK1/2, p-NF-κB, MMP1, and MMP9 were analyzed by Western blots.

Results: IL21 levels were elevated, while miR-361-5p was reduced in the synovial fluid from arthritic rats compared to healthy rats. IL21 was shown to suppress miR-361-5p in chondrocytes leading to hindered cell proliferation and increased apoptosis. Western blots indicated that miR-361-5p curbed MAP3K9 expression, reducing MMP activity by attenuating the ERK1/2/NF-κB pathway in chondrocytes.

Conclusion: IL21 upregulation and miR-361-5p downregulation characterize shoulder arthritis, resulting in MAP3K9 overexpression. This chain of molecular events boosts MMP expression in chondrocytes and exacerbates the condition’s progression.