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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Cytokines and Soluble Mediators in Immunity

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1630253

IL-19 suppresses Hippo signaling via modulating YAP1 phosphorylation in osteoarthritis

Provisionally accepted
Jiezhong  DengJiezhong Deng1Jun  GuJun Gu2Xiaoshan  GongXiaoshan Gong2Hao  TangHao Tang2Yuyi  CaiYuyi Cai3Yusheng  YangYusheng Yang1Shi-Wu  DongShi-Wu Dong2Chunrong  ZhaoChunrong Zhao2*
  • 1Southwest hospital, Chongqing, China
  • 2Army Medical University, Chongqing, China
  • 3Daping hospital, Chongqing, China

The final, formatted version of the article will be published soon.

Osteoarthritis (OA) is one of the most prevalent chronic degenerative diseases, characterized by the progressive destruction of joints, which is primarily evidenced by alterations in the phenotype of chondrocytes, chondrocyte apoptosis, and the progressive fibrosis of cartilage. Interleukin19 (IL-19) is predominantly expressed and secreted by B cells, monocytes, and macrophages. Recent studies have demonstrated that IL-19 attenuated inflammatory responses and facilitated tissue repair. However, no reported studies have explored the effects of IL-19 on osteoarthritis. We established an Interleukin 1β (IL-1β)-induced inflammation model and an anterior cruciate ligament transection (ACLT)-induced osteoarthritis model to validate the anti-inflammatory, anti-apoptotic, and osteoarthritis-delaying effects of IL-19. This study found an elevated expression of IL-19 in the joints of OA mice and confirmed that the IL-19 in these joints primarily derives from synovial M2 macrophages. Additionally, we found that IL-19 mitigates IL-1β-induced osteoarthritis by inhibiting the Hippo signaling pathway and the phosphorylation of the YAP1 (Yes-associated protein 1) protein. Furthermore, IL-19 represses the inflammatory response and apoptosis of IL-1β-induced chondrocytes, thereby helping to delay the progression of osteoarthritis.

Keywords: IL-19, M2 macrophages, Inflammation, Apoptosis, OA, Hippo-yap

Received: 17 May 2025; Accepted: 12 Sep 2025.

Copyright: © 2025 Deng, Gu, Gong, Tang, Cai, Yang, Dong and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Chunrong Zhao, Army Medical University, Chongqing, China

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