Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway
العنوان: | Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway |
---|---|
المؤلفون: | Chong Shen, Gang Zhong, Jun Yao, Jia Li, Ruiming Liang, Jianwei Liu, Tongmeng Jiang, Zhikang Miao, Li Zheng, Jinmin Zhao, Hui-Ping Lu, Huiping Long, Yiguan Le, Wei Su, Shiting Ma, Jun Luo |
المصدر: | Cellular Physiology and Biochemistry, Vol 51, Iss 6, Pp 2575-2590 (2018) |
بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2018. |
سنة النشر: | 2018 |
مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Wnt/β-catenin signaling pathway, Physiology, Interleukin-1beta, Anti-Inflammatory Agents, Chondrocyte, lcsh:Physiology, Proinflammatory cytokine, Rats, Sprague-Dawley, lcsh:Biochemistry, 03 medical and health sciences, Antimalarials, Young Adult, 0302 clinical medicine, Chondrocytes, Osteoarthritis, medicine, Animals, Humans, lcsh:QD415-436, Viability assay, Wnt Signaling Pathway, Cells, Cultured, Aged, lcsh:QP1-981, Chemistry, Cartilage, Wnt signaling pathway, Middle Aged, Artemisinins, Wnt Proteins, 030104 developmental biology, medicine.anatomical_structure, Apoptosis, 030220 oncology & carcinogenesis, Cancer research, Tumor necrosis factor alpha, Female, Artemisinin, Signal transduction |
الوصف: | Background/Aims: Current drug therapies for osteoarthritis (OA) are not practical because of the cytotoxicity and severe side-effects associated with most of them. Artemisinin (ART), an antimalarial agent, is well known for its safety and selectivity to kill injured cells. Based on its anti-inflammatory activity and role in the inhibition of OA-associated Wnt/β-catenin signaling pathway, which is crucial in the pathogenesis of OA, we hypothesized that ART might have an effect on OA. Methods: The chondro-protective and antiarthritic effects of ART on interleukin-1-beta (IL-1β)-induced and OA patient-derived chondrocytes were investigated in vitro using cell viability assay, glycosaminoglycan secretion, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blotting. We also used OA model rats constructed by anterior cruciate ligament transection and medial meniscus resection (ACLT+MMx) in the joints to investigate the effects of ART on OA by gross observation, morphological staining, immunohistochemistry, and enzyme-linked immunosorbent assay. Results: ART exhibited potent anti-inflammatory effects by inhibiting the expression of proinflammatory chemokines and cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor alpha, and matrix metallopeptidase-13. It also showed favorable chondro-protective effect as evidenced by enhanced cell proliferation and viability, increased glycosaminoglycan deposition, prevention of chondrocyte apoptosis, and degeneration of cartilage. Further, ART inhibited OA progression and cartilage degradation via the Wnt/β-catenin signaling pathway, suggesting that it might serve as a Wnt/β-catenin antagonist to reduce inflammation and prevent cartilage degradation. Conclusion: In conclusion, ART alleviates IL-1β-mediated inflammatory response and OA progression by regulating the Wnt/β-catenin signaling pathway. Thereby, it might be developed as a potential therapeutic agent for OA. |
اللغة: | English |
تدمد: | 1421-9778 1015-8987 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5be7f73fb64a587b1b58fab39f4d2f7 https://www.karger.com/Article/FullText/495926 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....e5be7f73fb64a587b1b58fab39f4d2f7 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14219778 10158987 |
---|