Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis

Yang Song,1,2 Dake Hao,3 Huan Jiang,4 Mingguang Huang,2 Qingjun Du,2 Yi Lin,2 Fei Liu,1 Bin Chen1 1Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Division of Traumatology and Joint,...

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Autores principales:	Song Y, Hao D, Jiang H, Huang M, Du Q, Lin Y, Liu F, Chen B
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	post-traumatic osteoarthritis synovium nrf2 chi3l1 oxidative stress inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/049a9e0eff544a5fbefcb0a1b8837387
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spelling	oai:doaj.org-article:049a9e0eff544a5fbefcb0a1b88373872021-12-02T18:01:08ZNrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis1178-7031https://doaj.org/article/049a9e0eff544a5fbefcb0a1b88373872021-08-01T00:00:00Zhttps://www.dovepress.com/nrf2-regulates-chi3l1-to-suppress-inflammation-and-improve-post-trauma-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Yang Song,1,2 Dake Hao,3 Huan Jiang,4 Mingguang Huang,2 Qingjun Du,2 Yi Lin,2 Fei Liu,1 Bin Chen1 1Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Division of Traumatology and Joint, Department of Orthopaedics, Shunde Hospital, Southern Medical University, Foshan, 528308, People’s Republic of China; 3Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA; 4Department of Anesthesiology, Shunde Hospital, Southern Medical University, Foshan, 528308, People’s Republic of ChinaCorrespondence: Bin ChenDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaEmail chb@smu.edu.cnIntroduction: Post-traumatic osteoarthritis (PTOA) is an inflammatory condition that occurs following mechanical joint trauma and that results in joint degeneration. This study sought to evaluate the regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in a murine model of anterior cruciate ligament transection (ACLT)-induced PTOA and in an in vitro model of synoviocyte inflammation induced by LPS treatment with the goal of exploring the role of chitinase 3-like-1 (CHI3L1) in this pathogenic context.Methods: PTOA model mice were intra-articularly injected with Nrf2 overexpression lentiviral vector, and safranin O-fast green staining as well as the Osteoarthritis Research Society International (OARSI) Scoring System were used to evaluate the severity of cartilage damage. Protein expression in the synovial tissue was evaluated by Western blotting, immunohistochemical staining, and ELISA. Additionally, murine synoviocytes were infected with Nrf2 overexpression lentivirus and stimulated with LPS. The levels of inflammatory cytokines were detected by ELISA. ROS levels were measured using dihydroethidium (DHE) dye.Results: We determined that the overexpression of Nrf2 was sufficient to reduce cartilage degradation in the context of PTOA in vivo, and we observed a significant decrease in the expression of matrix metalloproteinase 13 (MMP13) in the articular cartilage of samples from mice overexpressing Nrf2 relative to control mice. Synovial CHI3L1 expression and serum TNF-α, IL-1β, and IL-6 levels were reduced in animals overexpressing this transcription factor relative to PTOA model controls. Consistent with these findings, murine synoviocytes treated with LPS exhibited dose-dependent increases in ROS, TNF-α, IL-1β, IL-6, Nrf2, and CHI3L1 levels, whereas Nrf2 overexpression was sufficient to suppress these increases.Conclusion: Our data indicated that Nrf2 negatively regulates CHI3L1, suggesting that this signaling axis may regulate PTOA progression and may thus be a viable therapeutic target in individuals affected by this condition.Keywords: post-traumatic osteoarthritis, synovium, Nrf2, CHI3L1, oxidative stress, inflammationSong YHao DJiang HHuang MDu QLin YLiu FChen BDove Medical Pressarticlepost-traumatic osteoarthritissynoviumnrf2chi3l1oxidative stressinflammationPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 4079-4088 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	post-traumatic osteoarthritis synovium nrf2 chi3l1 oxidative stress inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	post-traumatic osteoarthritis synovium nrf2 chi3l1 oxidative stress inflammation Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Song Y Hao D Jiang H Huang M Du Q Lin Y Liu F Chen B Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis
description	Yang Song,1,2 Dake Hao,3 Huan Jiang,4 Mingguang Huang,2 Qingjun Du,2 Yi Lin,2 Fei Liu,1 Bin Chen1 1Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Division of Traumatology and Joint, Department of Orthopaedics, Shunde Hospital, Southern Medical University, Foshan, 528308, People’s Republic of China; 3Department of Surgery, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA; 4Department of Anesthesiology, Shunde Hospital, Southern Medical University, Foshan, 528308, People’s Republic of ChinaCorrespondence: Bin ChenDivision of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaEmail chb@smu.edu.cnIntroduction: Post-traumatic osteoarthritis (PTOA) is an inflammatory condition that occurs following mechanical joint trauma and that results in joint degeneration. This study sought to evaluate the regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in a murine model of anterior cruciate ligament transection (ACLT)-induced PTOA and in an in vitro model of synoviocyte inflammation induced by LPS treatment with the goal of exploring the role of chitinase 3-like-1 (CHI3L1) in this pathogenic context.Methods: PTOA model mice were intra-articularly injected with Nrf2 overexpression lentiviral vector, and safranin O-fast green staining as well as the Osteoarthritis Research Society International (OARSI) Scoring System were used to evaluate the severity of cartilage damage. Protein expression in the synovial tissue was evaluated by Western blotting, immunohistochemical staining, and ELISA. Additionally, murine synoviocytes were infected with Nrf2 overexpression lentivirus and stimulated with LPS. The levels of inflammatory cytokines were detected by ELISA. ROS levels were measured using dihydroethidium (DHE) dye.Results: We determined that the overexpression of Nrf2 was sufficient to reduce cartilage degradation in the context of PTOA in vivo, and we observed a significant decrease in the expression of matrix metalloproteinase 13 (MMP13) in the articular cartilage of samples from mice overexpressing Nrf2 relative to control mice. Synovial CHI3L1 expression and serum TNF-α, IL-1β, and IL-6 levels were reduced in animals overexpressing this transcription factor relative to PTOA model controls. Consistent with these findings, murine synoviocytes treated with LPS exhibited dose-dependent increases in ROS, TNF-α, IL-1β, IL-6, Nrf2, and CHI3L1 levels, whereas Nrf2 overexpression was sufficient to suppress these increases.Conclusion: Our data indicated that Nrf2 negatively regulates CHI3L1, suggesting that this signaling axis may regulate PTOA progression and may thus be a viable therapeutic target in individuals affected by this condition.Keywords: post-traumatic osteoarthritis, synovium, Nrf2, CHI3L1, oxidative stress, inflammation
format	article
author	Song Y Hao D Jiang H Huang M Du Q Lin Y Liu F Chen B
author_facet	Song Y Hao D Jiang H Huang M Du Q Lin Y Liu F Chen B
author_sort	Song Y
title	Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis
title_short	Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis
title_full	Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis
title_fullStr	Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis
title_full_unstemmed	Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis
title_sort	nrf2 regulates chi3l1 to suppress inflammation and improve post-traumatic osteoarthritis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/049a9e0eff544a5fbefcb0a1b8837387
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Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis

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