Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis
Increasing evidence has shown that macrophage pyroptosis in different tissues participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last studies also revealed the vital role of synovial fibroblast pyroptosis in the onset and development of knee osteoarthritis (KOA). In...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/2165918 |
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| author | Li Zhang Runlin Xing Zhengquan Huang Nongshan Zhang Li Zhang Xiaochen Li Peimin Wang |
| author_facet | Li Zhang Runlin Xing Zhengquan Huang Nongshan Zhang Li Zhang Xiaochen Li Peimin Wang |
| author_sort | Li Zhang |
| collection | DOAJ |
| description | Increasing evidence has shown that macrophage pyroptosis in different tissues participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last studies also revealed the vital role of synovial fibroblast pyroptosis in the onset and development of knee osteoarthritis (KOA). In this study, we aimed to investigate whether synovial macrophage pyroptosis did occur and whether this form of cell death should be related to synovitis and fibrosis of KOA. In the synovial tissue of KOA model rats, we observed a decrease of caspase1, NLRP3, ASC, and GSDMD caused by macrophage depletion in both the mRNA and protein expressions. Besides, rats treated with the specific caspase1 inhibitor Ac-YVAD-CMK showed less inflammatory reaction and fibrosis, not only in the expression of proinflammatory factors IL-1β, IL-18, and HMGB1 and fibrosis markers TGF-β, PLOD2, COL1A1, and TIMP1 but also in the observation of HE staining, Sirius Red staining, and the transverse diameters of the right knees. Subsequently, we established an LPS+ATP-induced model in macrophages mimicking the inflammatory environment of KOA and inducing macrophage pyroptosis. Macrophages transfected with caspase1 siRNA showed reduced cell death; meanwhile, the relative expression of pyroptosis-related proteins were also downregulated. In addition, the level of fibrotic markers in synovial fibroblasts were significantly decreased after coculture with siRNA GSDMD-transfected macrophages. To conclude, synovial macrophage pyroptosis may occur in the pathological processes of KOA and inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in KOA model rats. |
| format | Article |
| id | doaj-art-46471a94fdc641c6bfc306addc431901 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-46471a94fdc641c6bfc306addc4319012025-02-03T01:32:38ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/21659182165918Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee OsteoarthritisLi Zhang0Runlin Xing1Zhengquan Huang2Nongshan Zhang3Li Zhang4Xiaochen Li5Peimin Wang6The Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaThe Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaThe Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaThe Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaThe Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaThe Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaThe Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Orthopedics, Nanjing, ChinaIncreasing evidence has shown that macrophage pyroptosis in different tissues participates in chronic aseptic inflammation and is related to tissue fibrosis. Our last studies also revealed the vital role of synovial fibroblast pyroptosis in the onset and development of knee osteoarthritis (KOA). In this study, we aimed to investigate whether synovial macrophage pyroptosis did occur and whether this form of cell death should be related to synovitis and fibrosis of KOA. In the synovial tissue of KOA model rats, we observed a decrease of caspase1, NLRP3, ASC, and GSDMD caused by macrophage depletion in both the mRNA and protein expressions. Besides, rats treated with the specific caspase1 inhibitor Ac-YVAD-CMK showed less inflammatory reaction and fibrosis, not only in the expression of proinflammatory factors IL-1β, IL-18, and HMGB1 and fibrosis markers TGF-β, PLOD2, COL1A1, and TIMP1 but also in the observation of HE staining, Sirius Red staining, and the transverse diameters of the right knees. Subsequently, we established an LPS+ATP-induced model in macrophages mimicking the inflammatory environment of KOA and inducing macrophage pyroptosis. Macrophages transfected with caspase1 siRNA showed reduced cell death; meanwhile, the relative expression of pyroptosis-related proteins were also downregulated. In addition, the level of fibrotic markers in synovial fibroblasts were significantly decreased after coculture with siRNA GSDMD-transfected macrophages. To conclude, synovial macrophage pyroptosis may occur in the pathological processes of KOA and inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in KOA model rats.http://dx.doi.org/10.1155/2019/2165918 |
| spellingShingle | Li Zhang Runlin Xing Zhengquan Huang Nongshan Zhang Li Zhang Xiaochen Li Peimin Wang Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis Mediators of Inflammation |
| title | Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis |
| title_full | Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis |
| title_fullStr | Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis |
| title_full_unstemmed | Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis |
| title_short | Inhibition of Synovial Macrophage Pyroptosis Alleviates Synovitis and Fibrosis in Knee Osteoarthritis |
| title_sort | inhibition of synovial macrophage pyroptosis alleviates synovitis and fibrosis in knee osteoarthritis |
| url | http://dx.doi.org/10.1155/2019/2165918 |
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