Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis

Abstract Synovium hyperplasia characterizes joint diseases, such as rheumatoid arthritis (RA). The cytotoxic effect of low-dose Cadmium (Cd) was tested in vitro and ex vivo on synoviocytes, the mesenchymal key effector cells of inflammation and proliferation in arthritis. The anti-inflammatory and a...

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Autores principales: Paola Bonaventura, Guillaume Courbon, Aline Lamboux, Fabien Lavocat, Hubert Marotte, Francis Albarède, Pierre Miossec
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:ccdcf8d233f943d282a6462b0e13a5302021-12-02T16:07:58ZProtective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis10.1038/s41598-017-02611-52045-2322https://doaj.org/article/ccdcf8d233f943d282a6462b0e13a5302017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02611-5https://doaj.org/toc/2045-2322Abstract Synovium hyperplasia characterizes joint diseases, such as rheumatoid arthritis (RA). The cytotoxic effect of low-dose Cadmium (Cd) was tested in vitro and ex vivo on synoviocytes, the mesenchymal key effector cells of inflammation and proliferation in arthritis. The anti-inflammatory and anti-proliferative effects of Cd were tested in vivo by intra-articular injection in the adjuvant induced arthritis rat joints, where the clinical scores and the consequences of arthritis were evaluated. Cell death through apoptosis was highly induced by Cd in inflammatory synoviocytes (80% reduction of cell viability, p < 0.01). TNF plus IL-17 cytokine combination induced a two-fold increase of Cd cell content by enhancing the ZIP-8 importer and the MT-1 homeostasis regulator expression. Addition of Cd reduced IL-6 production in TNF plus IL-17-activated synoviocytes (up to 83%, p < 0.05) and in ex-vivo synovium biopsies (up to 94%, p < 0.01). Cd-injection in rat joints improved arthritis, reducing clinical scores (arthritic score reduced from 4 to 2, p < 0.01), inflammatory cell recruitment (up to 50%, p < 0.01) and protecting from bone/cartilage destruction. This proof of concept study is supported by the limited Cd spread in body reservoirs, with low-dose Cd providing a safe risk/benefit ratio, without toxic effects on other cell types and organs.Paola BonaventuraGuillaume CourbonAline LambouxFabien LavocatHubert MarotteFrancis AlbarèdePierre MiossecNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Paola Bonaventura
Guillaume Courbon
Aline Lamboux
Fabien Lavocat
Hubert Marotte
Francis Albarède
Pierre Miossec
Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
description Abstract Synovium hyperplasia characterizes joint diseases, such as rheumatoid arthritis (RA). The cytotoxic effect of low-dose Cadmium (Cd) was tested in vitro and ex vivo on synoviocytes, the mesenchymal key effector cells of inflammation and proliferation in arthritis. The anti-inflammatory and anti-proliferative effects of Cd were tested in vivo by intra-articular injection in the adjuvant induced arthritis rat joints, where the clinical scores and the consequences of arthritis were evaluated. Cell death through apoptosis was highly induced by Cd in inflammatory synoviocytes (80% reduction of cell viability, p < 0.01). TNF plus IL-17 cytokine combination induced a two-fold increase of Cd cell content by enhancing the ZIP-8 importer and the MT-1 homeostasis regulator expression. Addition of Cd reduced IL-6 production in TNF plus IL-17-activated synoviocytes (up to 83%, p < 0.05) and in ex-vivo synovium biopsies (up to 94%, p < 0.01). Cd-injection in rat joints improved arthritis, reducing clinical scores (arthritic score reduced from 4 to 2, p < 0.01), inflammatory cell recruitment (up to 50%, p < 0.01) and protecting from bone/cartilage destruction. This proof of concept study is supported by the limited Cd spread in body reservoirs, with low-dose Cd providing a safe risk/benefit ratio, without toxic effects on other cell types and organs.
format article
author Paola Bonaventura
Guillaume Courbon
Aline Lamboux
Fabien Lavocat
Hubert Marotte
Francis Albarède
Pierre Miossec
author_facet Paola Bonaventura
Guillaume Courbon
Aline Lamboux
Fabien Lavocat
Hubert Marotte
Francis Albarède
Pierre Miossec
author_sort Paola Bonaventura
title Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
title_short Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
title_full Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
title_fullStr Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
title_full_unstemmed Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
title_sort protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/ccdcf8d233f943d282a6462b0e13a530
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