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Published on: September 13, 2018
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.
Introduction:
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.
Method:
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.
Results:
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.
Conclusion:
IL-19 represses the inflammatory response and apoptosis of IL-1βw-induced chondrocytes, thereby helping to delay the progression of osteoarthritis.
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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