<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis

Osteoarthritis (OA) is a destructive disease of the joint with age and obesity being its most important risk factors. Around 50% of OA patients suffer from inflammation of the synovial joint capsule, which is characterized by increased abundance and activation of synovial macrophages that produce re...

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Autores principales:	Nik N. L. Kruisbergen, Irene Di Ceglie, Yvonne van Gemert, Birgitte Walgreen, Monique M. A. Helsen, Annet W. Slöetjes, Marije I. Koenders, Fons A. J. van de Loo, Johannes Roth, Thomas Vogl, Peter M. van der Kraan, Arjen B. Blom, Peter L. E. M. van Lent, Martijn H. J. van den Bosch
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	osteoarthritis ROS Macrophages NOX2 low-density lipoprotein Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/78cf3de17a744173a88dbeea58163c1d
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spelling	oai:doaj.org-article:78cf3de17a744173a88dbeea58163c1d2021-11-25T16:25:33Z<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis10.3390/antiox101116602076-3921https://doaj.org/article/78cf3de17a744173a88dbeea58163c1d2021-10-01T00:00:00Zhttps://www.mdpi.com/2076-3921/10/11/1660https://doaj.org/toc/2076-3921Osteoarthritis (OA) is a destructive disease of the joint with age and obesity being its most important risk factors. Around 50% of OA patients suffer from inflammation of the synovial joint capsule, which is characterized by increased abundance and activation of synovial macrophages that produce reactive oxygen species (ROS) via NADPH-oxidase 2 (NOX2). Both ROS and high blood levels of low-density lipoprotein (LDL) are implicated in OA pathophysiology, which may interact to form oxidized LDL (oxLDL) and thereby promote disease. Therefore, targeting NOX2 could be a viable treatment strategy for OA. Collagenase-induced OA (CiOA) was used to compare pathology between wild-type (WT) and Nox2 knockout (<i>Nox2<sup>−/−</sup></i>) C57Bl/6 mice. Mice were either fed a standard diet or Western diet (WD) to study a possible interaction between NOX2-derived ROS and LDL. Synovial inflammation, cartilage damage and ectopic bone size were assessed on histology. Extracellular ROS production by macrophages was measured in vitro using the Amplex Red assay. <i>Nox2<sup>−/−</sup></i> macrophages produced basal levels of ROS but were unable to increase ROS production in response to the alarmin S100A8 or the phorbol ester PMA. Interestingly, <i>Nox2</i> deficiency reduced cartilage damage, synovial lining thickness and ectopic bone size, whereas these disease parameters were not affected by WD-feeding. These results suggest that NOX2-derived ROS are involved in CiOA development.Nik N. L. KruisbergenIrene Di CeglieYvonne van GemertBirgitte WalgreenMonique M. A. HelsenAnnet W. SlöetjesMarije I. KoendersFons A. J. van de LooJohannes RothThomas VoglPeter M. van der KraanArjen B. BlomPeter L. E. M. van LentMartijn H. J. van den BoschMDPI AGarticleosteoarthritisROSMacrophagesNOX2low-density lipoproteinTherapeutics. PharmacologyRM1-950ENAntioxidants, Vol 10, Iss 1660, p 1660 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	osteoarthritis ROS Macrophages NOX2 low-density lipoprotein Therapeutics. Pharmacology RM1-950
spellingShingle	osteoarthritis ROS Macrophages NOX2 low-density lipoprotein Therapeutics. Pharmacology RM1-950 Nik N. L. Kruisbergen Irene Di Ceglie Yvonne van Gemert Birgitte Walgreen Monique M. A. Helsen Annet W. Slöetjes Marije I. Koenders Fons A. J. van de Loo Johannes Roth Thomas Vogl Peter M. van der Kraan Arjen B. Blom Peter L. E. M. van Lent Martijn H. J. van den Bosch <i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
description	Osteoarthritis (OA) is a destructive disease of the joint with age and obesity being its most important risk factors. Around 50% of OA patients suffer from inflammation of the synovial joint capsule, which is characterized by increased abundance and activation of synovial macrophages that produce reactive oxygen species (ROS) via NADPH-oxidase 2 (NOX2). Both ROS and high blood levels of low-density lipoprotein (LDL) are implicated in OA pathophysiology, which may interact to form oxidized LDL (oxLDL) and thereby promote disease. Therefore, targeting NOX2 could be a viable treatment strategy for OA. Collagenase-induced OA (CiOA) was used to compare pathology between wild-type (WT) and Nox2 knockout (<i>Nox2<sup>−/−</sup></i>) C57Bl/6 mice. Mice were either fed a standard diet or Western diet (WD) to study a possible interaction between NOX2-derived ROS and LDL. Synovial inflammation, cartilage damage and ectopic bone size were assessed on histology. Extracellular ROS production by macrophages was measured in vitro using the Amplex Red assay. <i>Nox2<sup>−/−</sup></i> macrophages produced basal levels of ROS but were unable to increase ROS production in response to the alarmin S100A8 or the phorbol ester PMA. Interestingly, <i>Nox2</i> deficiency reduced cartilage damage, synovial lining thickness and ectopic bone size, whereas these disease parameters were not affected by WD-feeding. These results suggest that NOX2-derived ROS are involved in CiOA development.
format	article
author	Nik N. L. Kruisbergen Irene Di Ceglie Yvonne van Gemert Birgitte Walgreen Monique M. A. Helsen Annet W. Slöetjes Marije I. Koenders Fons A. J. van de Loo Johannes Roth Thomas Vogl Peter M. van der Kraan Arjen B. Blom Peter L. E. M. van Lent Martijn H. J. van den Bosch
author_facet	Nik N. L. Kruisbergen Irene Di Ceglie Yvonne van Gemert Birgitte Walgreen Monique M. A. Helsen Annet W. Slöetjes Marije I. Koenders Fons A. J. van de Loo Johannes Roth Thomas Vogl Peter M. van der Kraan Arjen B. Blom Peter L. E. M. van Lent Martijn H. J. van den Bosch
author_sort	Nik N. L. Kruisbergen
title	<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
title_short	<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
title_full	<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
title_fullStr	<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
title_full_unstemmed	<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis
title_sort	<i>nox</i>2 deficiency reduces cartilage damage and ectopic bone formation in an experimental model for osteoarthritis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/78cf3de17a744173a88dbeea58163c1d
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<i>Nox</i>2 Deficiency Reduces Cartilage Damage and Ectopic Bone Formation in an Experimental Model for Osteoarthritis

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