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Hokkaido University Collection of Scholarly and Academic Papers >
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Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis
| Title: | Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis |
| Authors: | Ebata, Taku Browse this author | | Terkawi, Mohamad Alaa Browse this author | | Hamasaki, Masanari Browse this author | | Matsumae, Gen Browse this author | | Onodera, Tomohiro Browse this author →KAKEN DB | | Aly, Mahmoud Khamis Browse this author | | Yokota, Shunichi Browse this author | | Alhasan, Hend Browse this author | | Shimizu, Tomohiro Browse this author | | Takahashi, Daisuke Browse this author | | Homan, Kentaro Browse this author | | Kadoya, Ken Browse this author | | Iwasaki, Norimasa Browse this author →KAKEN DB |
| Issue Date: | 25-Jun-2021 |
| Publisher: | Cell Press |
| Journal Title: | iScience |
| Volume: | 24 |
| Issue: | 6 |
| Start Page: | 102643 |
| Publisher DOI: | 10.1016/j.isci.2021.102643 |
| Abstract: | Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82552 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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