Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model

Abstract Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in vario...

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Autores principales:	Guillaume Courbon, Raphaëlle Lamarque, Maude Gerbaix, Robin Caire, Marie-Thérèse Linossier, Norbert Laroche, Mireille Thomas, Thierry Thomas, Laurence Vico, Hubert Marotte
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3324459e446043919c514f7d03b843cf
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spelling	oai:doaj.org-article:3324459e446043919c514f7d03b843cf2021-12-02T12:32:48ZEarly sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model10.1038/s41598-018-21886-w2045-2322https://doaj.org/article/3324459e446043919c514f7d03b843cf2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21886-whttps://doaj.org/toc/2045-2322Abstract Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.Guillaume CourbonRaphaëlle LamarqueMaude GerbaixRobin CaireMarie-Thérèse LinossierNorbert LarocheMireille ThomasThierry ThomasLaurence VicoHubert MarotteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guillaume Courbon Raphaëlle Lamarque Maude Gerbaix Robin Caire Marie-Thérèse Linossier Norbert Laroche Mireille Thomas Thierry Thomas Laurence Vico Hubert Marotte Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
description	Abstract Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.
format	article
author	Guillaume Courbon Raphaëlle Lamarque Maude Gerbaix Robin Caire Marie-Thérèse Linossier Norbert Laroche Mireille Thomas Thierry Thomas Laurence Vico Hubert Marotte
author_facet	Guillaume Courbon Raphaëlle Lamarque Maude Gerbaix Robin Caire Marie-Thérèse Linossier Norbert Laroche Mireille Thomas Thierry Thomas Laurence Vico Hubert Marotte
author_sort	Guillaume Courbon
title	Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
title_short	Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
title_full	Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
title_fullStr	Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
title_full_unstemmed	Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
title_sort	early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3324459e446043919c514f7d03b843cf
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Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model

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