Abstract | OBJECTIVE: The severity of osteoarthritis (OA) and cartilage degeneration is highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. We undertook this study to explore the pathologic role of inflammatory macrophage extracellular vesicles (EVs) in cartilage degeneration. METHODS: RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-sequencing analyses of stimulated chondrocytes indicated that up-regulated genes were mainly categorized into apoptotic process and tumor necrosis factor signaling pathways, which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase 11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and pathologic changes in collagenase-induced and joint instability-induced OA models. CONCLUSION: Our results provide new insight into the pathologic mechanisms of OA and suggest that noncanonical pyroptosis in chondrocytes represents an attractive therapeutic target for treatment.
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Authors | Taku Ebata, Mohamad Alaa Terkawi, Keita Kitahara, Shunichi Yokota, Junki Shiota, Yoshio Nishida, Gen Matsumae, Hend Alhasan, Masanari Hamasaki, Kazutoshi Hontani, Tomohiro Shimizu, Daisuke Takahashi, Tsutomu Endo, Tomohiro Onodera, Ken Kadoya, Norimasa Iwasaki |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 75
Issue 8
Pg. 1358-1369
(08 2023)
ISSN: 2326-5205 [Electronic] United States |
PMID | 36924130
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2023 American College of Rheumatology. |
Chemical References |
- RNA, Small Interfering
- Caspases
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Topics |
- Mice
- Animals
- Chondrocytes
(metabolism)
- Pyroptosis
- Cartilage
(metabolism)
- Osteoarthritis
(metabolism)
- Macrophages
(metabolism)
- RNA, Small Interfering
(metabolism)
- Caspases
- Extracellular Vesicles
(pathology)
- Cartilage, Articular
(metabolism)
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