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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Main Authors: Song Y, Hao D, Jiang H, Huang M, Du Q, Lin Y, Liu F, Chen B
Format: Article
Language:English
Published: Dove Medical Press 2021-08-01
Series:Journal of Inflammation Research
Subjects:
Online Access:https://www.dovepress.com/nrf2-regulates-chi3l1-to-suppress-inflammation-and-improve-post-trauma-peer-reviewed-fulltext-article-JIR
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spelling doaj-049a9e0eff544a5fbefcb0a1b88373872021-08-24T20:06:34ZengDove Medical PressJournal of Inflammation Research1178-70312021-08-01Volume 144079408868112Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic OsteoarthritisSong YHao DJiang HHuang MDu QLin YLiu FChen BYang 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, inflammationhttps://www.dovepress.com/nrf2-regulates-chi3l1-to-suppress-inflammation-and-improve-post-trauma-peer-reviewed-fulltext-article-JIRpost-traumatic osteoarthritissynoviumnrf2chi3l1oxidative stressinflammation
collection DOAJ
language English
format Article
sources DOAJ
author Song Y
Hao D
Jiang H
Huang M
Du Q
Lin Y
Liu F
Chen B
spellingShingle 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
Journal of Inflammation Research
post-traumatic osteoarthritis
synovium
nrf2
chi3l1
oxidative stress
inflammation
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
series Journal of Inflammation Research
issn 1178-7031
publishDate 2021-08-01
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
topic post-traumatic osteoarthritis
synovium
nrf2
chi3l1
oxidative stress
inflammation
url https://www.dovepress.com/nrf2-regulates-chi3l1-to-suppress-inflammation-and-improve-post-trauma-peer-reviewed-fulltext-article-JIR
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