T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway
Abstract Background The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism. Methods In this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to o...
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BMC
2021-06-01
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Series: | Journal of Orthopaedic Surgery and Research |
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Online Access: | https://doi.org/10.1186/s13018-021-02530-2 |
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author | Shan Cong Yan Meng Lingrui Wang Jiao Sun Ta bu shi·Nu er xia ti Li Luo |
author_facet | Shan Cong Yan Meng Lingrui Wang Jiao Sun Ta bu shi·Nu er xia ti Li Luo |
author_sort | Shan Cong |
collection | DOAJ |
description | Abstract Background The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism. Methods In this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to observe the pathological changes of cartilage tissue and Mankin scoring principle was used for quantitative scoring. Transmission electron microscopy (TEM) was applied to observe the ultrastructure of cartilage tissue. ELISA was used to measure the levels of matrix metalloproteinase 13 (MMP-13) and inflammatory factors (interleukin (IL)-6 and tumor necrosis factor a (TNF-a)) in serum. RT-qPCR and immunohistochemistry were conducted to detect mRNA expression and protein expression of key genes in Wnt/β-catenin pathway. Results H&E, Mankin scoring, and TEM data confirmed that compared with model group, T-614 significantly improved the degeneration of articular cartilage. Besides, we observed that low, middle, and high doses of T-614 could decrease the levels of MMP13, TNF-α, and IL-6 in serum to different degrees. Mechanically, T-614 downregulated the mRNA and protein expression of β-catenin and MMP13 in cartilage tissue via a dose-dependent manner, and on the contrary upregulated the mRNA and protein expression of glucogen synthase kinase-3 beta (GSK-3β). Conclusion Our results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage. |
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issn | 1749-799X |
language | English |
last_indexed | 2024-04-11T18:38:24Z |
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series | Journal of Orthopaedic Surgery and Research |
spelling | doaj.art-43338fa5f51e4198b3cd3e2e08f74eb02022-12-22T04:09:08ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-06-0116111010.1186/s13018-021-02530-2T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathwayShan Cong0Yan Meng1Lingrui Wang2Jiao Sun3Ta bu shi·Nu er xia ti4Li Luo5Department of Rheumatism and Immunology, First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Rheumatism and Immunology, First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Rheumatism and Immunology, Xinjiang Medical UniversityDepartment of Rheumatism and Immunology, First Affiliated Hospital of Xinjiang Medical UniversityDepartment of Rheumatism and Immunology, The Second Affiliated Hospital of Xinjiang Medical UniversityDepartment of Rheumatism and Immunology, First Affiliated Hospital of Xinjiang Medical UniversityAbstract Background The aim of this study was to investigate the effect of Iguratimod (T-614) on rat knee osteoarthritis (KOA) and further to explore its underlying mechanism. Methods In this study, papain-induced KOA model was constructed. Hematoxylin and eosin (H&E) staining was conducted to observe the pathological changes of cartilage tissue and Mankin scoring principle was used for quantitative scoring. Transmission electron microscopy (TEM) was applied to observe the ultrastructure of cartilage tissue. ELISA was used to measure the levels of matrix metalloproteinase 13 (MMP-13) and inflammatory factors (interleukin (IL)-6 and tumor necrosis factor a (TNF-a)) in serum. RT-qPCR and immunohistochemistry were conducted to detect mRNA expression and protein expression of key genes in Wnt/β-catenin pathway. Results H&E, Mankin scoring, and TEM data confirmed that compared with model group, T-614 significantly improved the degeneration of articular cartilage. Besides, we observed that low, middle, and high doses of T-614 could decrease the levels of MMP13, TNF-α, and IL-6 in serum to different degrees. Mechanically, T-614 downregulated the mRNA and protein expression of β-catenin and MMP13 in cartilage tissue via a dose-dependent manner, and on the contrary upregulated the mRNA and protein expression of glucogen synthase kinase-3 beta (GSK-3β). Conclusion Our results suggested that T-614 can reduce the level of its downstream target gene MMP-13 and downregulate the expression of inflammatory cytokines TNF-α and IL-6 by regulating the Wnt/β-catenin signaling pathway, thereby inhibiting joint inflammation and controlling KOA degeneration of articular cartilage.https://doi.org/10.1186/s13018-021-02530-2Knee osteoarthritisArticular cartilageIguratimodInflammationWnt/β-catenin signaling pathway |
spellingShingle | Shan Cong Yan Meng Lingrui Wang Jiao Sun Ta bu shi·Nu er xia ti Li Luo T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway Journal of Orthopaedic Surgery and Research Knee osteoarthritis Articular cartilage Iguratimod Inflammation Wnt/β-catenin signaling pathway |
title | T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway |
title_full | T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway |
title_fullStr | T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway |
title_full_unstemmed | T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway |
title_short | T-614 attenuates knee osteoarthritis via regulating Wnt/β-catenin signaling pathway |
title_sort | t 614 attenuates knee osteoarthritis via regulating wnt β catenin signaling pathway |
topic | Knee osteoarthritis Articular cartilage Iguratimod Inflammation Wnt/β-catenin signaling pathway |
url | https://doi.org/10.1186/s13018-021-02530-2 |
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