Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory

Abstract High uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chond...

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Autores principales:	Jenn-Haung Lai, Shue-Fen Luo, Li-Feng Hung, Chuan-Yueh Huang, Shiu-Bii Lien, Leou-Chyr Lin, Feng-Cheng Liu, B. Linju Yen, Ling-Jun Ho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1447b46164c4cfa94d509fe2161f70b
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spelling	oai:doaj.org-article:e1447b46164c4cfa94d509fe2161f70b2021-12-02T12:32:13ZPhysiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory10.1038/s41598-017-02640-02045-2322https://doaj.org/article/e1447b46164c4cfa94d509fe2161f70b2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02640-0https://doaj.org/toc/2045-2322Abstract High uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chondrocytes and mice with collagen-induced arthritis (CIA) were examined. We showed that sUA inhibited TNF-α- and interleukin (IL)-1β–induced inducible nitric oxide synthase, cyclooxygenase-2 and matrix metalloproteinase (MMP)-13 expression. Examination of the mRNA expression of several MMPs and aggrecanases confirmed that sUA exerts chondroprotective effects by inhibiting the activity of many chondro-destructive enzymes. These effects attenuated collagen II loss in chondrocytes and reduced proteoglycan degradation in cartilage explants. These results were reproduced in chondrocytes cultured in three-dimensional (3-D) alginate beads. Molecular studies revealed that sUA inhibited the ERK/AP-1 signalling pathway, but not the IκBα-NF-κB signalling pathway. Increases in plasma uric acid levels facilitated by the provision of oxonic acid, a uricase inhibitor, to CIA mice exerted both anti-inflammatory and arthroprotective effects in these animals, as demonstrated by their arthritis severity scores and immunohistochemical analysis results. Our study demonstrated that physiological concentrations of sUA displayed anti-inflammatory and chondroprotective effects both in vitro and in vivo.Jenn-Haung LaiShue-Fen LuoLi-Feng HungChuan-Yueh HuangShiu-Bii LienLeou-Chyr LinFeng-Cheng LiuB. Linju YenLing-Jun HoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jenn-Haung Lai Shue-Fen Luo Li-Feng Hung Chuan-Yueh Huang Shiu-Bii Lien Leou-Chyr Lin Feng-Cheng Liu B. Linju Yen Ling-Jun Ho Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
description	Abstract High uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chondrocytes and mice with collagen-induced arthritis (CIA) were examined. We showed that sUA inhibited TNF-α- and interleukin (IL)-1β–induced inducible nitric oxide synthase, cyclooxygenase-2 and matrix metalloproteinase (MMP)-13 expression. Examination of the mRNA expression of several MMPs and aggrecanases confirmed that sUA exerts chondroprotective effects by inhibiting the activity of many chondro-destructive enzymes. These effects attenuated collagen II loss in chondrocytes and reduced proteoglycan degradation in cartilage explants. These results were reproduced in chondrocytes cultured in three-dimensional (3-D) alginate beads. Molecular studies revealed that sUA inhibited the ERK/AP-1 signalling pathway, but not the IκBα-NF-κB signalling pathway. Increases in plasma uric acid levels facilitated by the provision of oxonic acid, a uricase inhibitor, to CIA mice exerted both anti-inflammatory and arthroprotective effects in these animals, as demonstrated by their arthritis severity scores and immunohistochemical analysis results. Our study demonstrated that physiological concentrations of sUA displayed anti-inflammatory and chondroprotective effects both in vitro and in vivo.
format	article
author	Jenn-Haung Lai Shue-Fen Luo Li-Feng Hung Chuan-Yueh Huang Shiu-Bii Lien Leou-Chyr Lin Feng-Cheng Liu B. Linju Yen Ling-Jun Ho
author_facet	Jenn-Haung Lai Shue-Fen Luo Li-Feng Hung Chuan-Yueh Huang Shiu-Bii Lien Leou-Chyr Lin Feng-Cheng Liu B. Linju Yen Ling-Jun Ho
author_sort	Jenn-Haung Lai
title	Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
title_short	Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
title_full	Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
title_fullStr	Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
title_full_unstemmed	Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
title_sort	physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e1447b46164c4cfa94d509fe2161f70b
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Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory

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