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

Jiezhong Deng1, Jun Gu2,3, Xiaoshan Gong2

  • 1Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing, China.

Frontiers in Immunology
|October 17, 2025
PubMed
Abstract

Insights

Interleukin-19 (IL-19) delays osteoarthritis progression by reducing inflammation and chondrocyte apoptosis. This study found IL-19 inhibits the Hippo signaling pathway, offering a potential therapeutic target for osteoarthritis.

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Osteoarthritis (OA) is a prevalent degenerative joint disease.
  • Chondrocyte dysfunction, apoptosis, and cartilage fibrosis characterize OA.
  • Interleukin-19 (IL-19) has known anti-inflammatory and tissue-repair roles, but its effect on OA is unexplored.

Purpose of the Study:

  • To investigate the role and therapeutic potential of IL-19 in osteoarthritis.
  • To determine if IL-19 can mitigate inflammation and apoptosis in osteoarthritis models.

Main Methods:

  • Established Interleukin 1β (IL-1β)-induced inflammation and ACLT-induced osteoarthritis mouse models.
  • Quantified IL-19 expression in OA joints and identified its cellular source (synovial M2 macrophages).
  • Assessed the impact of IL-19 on the Hippo signaling pathway and YAP1 phosphorylation.

Main Results:

  • IL-19 expression was elevated in the joints of OA mice, originating from M2 macrophages.
  • IL-19 demonstrated anti-inflammatory and anti-apoptotic effects on IL-1β-induced chondrocytes.
  • IL-19 mitigated osteoarthritis progression by inhibiting the Hippo signaling pathway and YAP1 phosphorylation.

Conclusions:

  • IL-19 plays a protective role in osteoarthritis by suppressing inflammation and chondrocyte apoptosis.
  • Inhibition of the Hippo signaling pathway by IL-19 is a key mechanism in its OA-protective effects.
  • IL-19 represents a potential therapeutic agent for delaying osteoarthritis progression.

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