Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.

<h4>Introduction</h4>Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molec...

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Autores principales:	Vesa-Petteri Kouri, Juri Olkkonen, Emilia Kaivosoja, Mari Ainola, Juuso Juhila, Iiris Hovatta, Yrjö T Konttinen, Jami Mandelin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a82eb79d24f4cc980665e0d9b1e4821
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spelling	oai:doaj.org-article:6a82eb79d24f4cc980665e0d9b1e48212021-11-18T08:01:24ZCircadian timekeeping is disturbed in rheumatoid arthritis at molecular level.1932-620310.1371/journal.pone.0054049https://doaj.org/article/6a82eb79d24f4cc980665e0d9b1e48212013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23335987/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Introduction</h4>Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molecular machinery responsible for the circadian timekeeping is perturbed in RA. The aim of this study was to investigate the expression of circadian clock in RA.<h4>Methods</h4>Gene expression of thirteen clock genes was analyzed in the synovial membrane of RA and control osteoarthritis (OA) patients. BMAL1 protein was detected using immunohistochemistry. Cell autonomous clock oscillation was started in RA and OA synovial fibroblasts using serum shock. The effect of pro-inflammatory stimulus on clock gene expression in synovial fibroblasts was studied using IL-6 and TNF-α.<h4>Results</h4>Gene expression analysis disclosed disconcerted circadian timekeeping and immunohistochemistry revealed strong cytoplasmic localization of BMAL1 in RA patients. Perturbed circadian timekeeping is at least in part inflammation independent and cell autonomous, because RA synovial fibroblasts display altered circadian expression of several clock components, and perturbed circadian production of IL-6 and IL-1β after clock resetting. However, inflammatory stimulus disturbs the rhythm in cultured fibroblasts. Throughout the experiments ARNTL2 and NPAS2 appeared to be the most affected clock genes in human immune-inflammatory conditions.<h4>Conclusion</h4>We conclude that the molecular machinery controlling the circadian rhythm is disturbed in RA patients.Vesa-Petteri KouriJuri OlkkonenEmilia KaivosojaMari AinolaJuuso JuhilaIiris HovattaYrjö T KonttinenJami MandelinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54049 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vesa-Petteri Kouri Juri Olkkonen Emilia Kaivosoja Mari Ainola Juuso Juhila Iiris Hovatta Yrjö T Konttinen Jami Mandelin Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
description	<h4>Introduction</h4>Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molecular machinery responsible for the circadian timekeeping is perturbed in RA. The aim of this study was to investigate the expression of circadian clock in RA.<h4>Methods</h4>Gene expression of thirteen clock genes was analyzed in the synovial membrane of RA and control osteoarthritis (OA) patients. BMAL1 protein was detected using immunohistochemistry. Cell autonomous clock oscillation was started in RA and OA synovial fibroblasts using serum shock. The effect of pro-inflammatory stimulus on clock gene expression in synovial fibroblasts was studied using IL-6 and TNF-α.<h4>Results</h4>Gene expression analysis disclosed disconcerted circadian timekeeping and immunohistochemistry revealed strong cytoplasmic localization of BMAL1 in RA patients. Perturbed circadian timekeeping is at least in part inflammation independent and cell autonomous, because RA synovial fibroblasts display altered circadian expression of several clock components, and perturbed circadian production of IL-6 and IL-1β after clock resetting. However, inflammatory stimulus disturbs the rhythm in cultured fibroblasts. Throughout the experiments ARNTL2 and NPAS2 appeared to be the most affected clock genes in human immune-inflammatory conditions.<h4>Conclusion</h4>We conclude that the molecular machinery controlling the circadian rhythm is disturbed in RA patients.
format	article
author	Vesa-Petteri Kouri Juri Olkkonen Emilia Kaivosoja Mari Ainola Juuso Juhila Iiris Hovatta Yrjö T Konttinen Jami Mandelin
author_facet	Vesa-Petteri Kouri Juri Olkkonen Emilia Kaivosoja Mari Ainola Juuso Juhila Iiris Hovatta Yrjö T Konttinen Jami Mandelin
author_sort	Vesa-Petteri Kouri
title	Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
title_short	Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
title_full	Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
title_fullStr	Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
title_full_unstemmed	Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
title_sort	circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/6a82eb79d24f4cc980665e0d9b1e4821
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Circadian timekeeping is disturbed in rheumatoid arthritis at molecular level.

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