Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats

Context: Dexmedetomidine (Dex) has been reported to have an anti-inflammatory effect. However, its role on osteoarthritis (OA) has not been explored. Objective: This study investigates the effect of Dex on OA rat model induced by papain. Materials and methods: The OA Wistar rat model was induced by...

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Autores principales:	Fang Cheng, Feng-Feng Yan, Yue-Peng Liu, Yan Cong, Ke-Fu Sun, Xue-Ming He
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	joint pain inflammation paw withdrawal mechanical threshold paw withdrawal thermal latency articular cartilage Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ab64ca84b5ff4eb89df9617460e3d4c3
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spelling	oai:doaj.org-article:ab64ca84b5ff4eb89df9617460e3d4c32021-11-17T14:21:56ZDexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats1388-02091744-511610.1080/13880209.2019.1651874https://doaj.org/article/ab64ca84b5ff4eb89df9617460e3d4c32019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1651874https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Dexmedetomidine (Dex) has been reported to have an anti-inflammatory effect. However, its role on osteoarthritis (OA) has not been explored. Objective: This study investigates the effect of Dex on OA rat model induced by papain. Materials and methods: The OA Wistar rat model was induced by intraluminal injection of 20 mL of papain mixed solution (4% papain 0.2 mL mixed with 0.03 mol L−1 l-cysteine 0.1 mL) into the right knee joint. Two weeks after papain injection, OA rats were treated by intra-articular injection of Dex (5, 10, or 20 μg kg−1) into the right knee (once a day, continuously for 4 weeks). Articular cartilage tissue was obtained after Dex treatment was completed. Results: The gait behavior scores (2.83 ± 0.49), PWMT (15.2 ± 1.78) and PTWL (14.81 ± 0.92) in H-DEX group were higher than that of OA group, while Mankin score (5.5 ± 0.81) was decreased (p < 0.05). Compared with the OA group, the IL-1β (153.11 ± 16.05 pg mg−1), IL-18 (3.71 ± 0.7 pg mg−1), IL-6 (14.15 ± 1.94 pg/mg) and TNF-α (40.45 ± 10.28 pg mg−1) levels in H-DEX group were decreased (p < 0.05). MMP-13, NLRP3, and caspase-1 p10 expression in Dex groups were significantly lower than that of OA group (p < 0.05), while collagen II was increased (p < 0.05). p65 in the nucleus of Dex groups was significantly down-regulated than that of OA group (p < 0.05). Discussion and Conclusions: Dex can improve pain symptoms and cartilage tissue damage of OA rats, which may be related to its inhibition of the activation of NF-κB and NLRP3 inflammasome.Fang ChengFeng-Feng YanYue-Peng LiuYan CongKe-Fu SunXue-Ming HeTaylor & Francis Grouparticlejoint paininflammationpaw withdrawal mechanical thresholdpaw withdrawal thermal latencyarticular cartilageTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 649-659 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	joint pain inflammation paw withdrawal mechanical threshold paw withdrawal thermal latency articular cartilage Therapeutics. Pharmacology RM1-950
spellingShingle	joint pain inflammation paw withdrawal mechanical threshold paw withdrawal thermal latency articular cartilage Therapeutics. Pharmacology RM1-950 Fang Cheng Feng-Feng Yan Yue-Peng Liu Yan Cong Ke-Fu Sun Xue-Ming He Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats
description	Context: Dexmedetomidine (Dex) has been reported to have an anti-inflammatory effect. However, its role on osteoarthritis (OA) has not been explored. Objective: This study investigates the effect of Dex on OA rat model induced by papain. Materials and methods: The OA Wistar rat model was induced by intraluminal injection of 20 mL of papain mixed solution (4% papain 0.2 mL mixed with 0.03 mol L−1 l-cysteine 0.1 mL) into the right knee joint. Two weeks after papain injection, OA rats were treated by intra-articular injection of Dex (5, 10, or 20 μg kg−1) into the right knee (once a day, continuously for 4 weeks). Articular cartilage tissue was obtained after Dex treatment was completed. Results: The gait behavior scores (2.83 ± 0.49), PWMT (15.2 ± 1.78) and PTWL (14.81 ± 0.92) in H-DEX group were higher than that of OA group, while Mankin score (5.5 ± 0.81) was decreased (p < 0.05). Compared with the OA group, the IL-1β (153.11 ± 16.05 pg mg−1), IL-18 (3.71 ± 0.7 pg mg−1), IL-6 (14.15 ± 1.94 pg/mg) and TNF-α (40.45 ± 10.28 pg mg−1) levels in H-DEX group were decreased (p < 0.05). MMP-13, NLRP3, and caspase-1 p10 expression in Dex groups were significantly lower than that of OA group (p < 0.05), while collagen II was increased (p < 0.05). p65 in the nucleus of Dex groups was significantly down-regulated than that of OA group (p < 0.05). Discussion and Conclusions: Dex can improve pain symptoms and cartilage tissue damage of OA rats, which may be related to its inhibition of the activation of NF-κB and NLRP3 inflammasome.
format	article
author	Fang Cheng Feng-Feng Yan Yue-Peng Liu Yan Cong Ke-Fu Sun Xue-Ming He
author_facet	Fang Cheng Feng-Feng Yan Yue-Peng Liu Yan Cong Ke-Fu Sun Xue-Ming He
author_sort	Fang Cheng
title	Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats
title_short	Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats
title_full	Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats
title_fullStr	Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats
title_full_unstemmed	Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats
title_sort	dexmedetomidine inhibits the nf-κb pathway and nlrp3 inflammasome to attenuate papain-induced osteoarthritis in rats
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/ab64ca84b5ff4eb89df9617460e3d4c3
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Dexmedetomidine inhibits the NF-κB pathway and NLRP3 inflammasome to attenuate papain-induced osteoarthritis in rats

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