Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.

Patients with systemic lupus erythematosus are at increased risk for alveolar bone loss due to periodontitis possibly as a result of a pathogenic immune response to oral bacteria and inflammation. The aim of the present study was to investigate whether an anti-TNF-α antagonist could prevent mandibul...

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Autores principales:	Nithidol Sakunrangsit, Piyanuch Metheepakornchai, Sarinya Kumpunya, Matthew Blake Greenblatt, Asada Leelahavanichkul, Prapaporn Pisitkun, Sutada Lotinun
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/884279d1b9c24f5fa2f526bb2db3d737
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spelling	oai:doaj.org-article:884279d1b9c24f5fa2f526bb2db3d7372021-12-02T20:11:26ZEtanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.1932-620310.1371/journal.pone.0250215https://doaj.org/article/884279d1b9c24f5fa2f526bb2db3d7372021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0250215https://doaj.org/toc/1932-6203Patients with systemic lupus erythematosus are at increased risk for alveolar bone loss due to periodontitis possibly as a result of a pathogenic immune response to oral bacteria and inflammation. The aim of the present study was to investigate whether an anti-TNF-α antagonist could prevent mandibular bone loss in the FcγRIIb-/- mouse model of lupus. Mice lacking FcγRIIb had decreased cancellous and cortical bone volume at 6 months of age. Etanercept increased cancellous but not cortical bone volume in WT and increased both cancellous bone volume and cortical thickness in FcγRIIb-deficient mice. FcγRIIb deficiency decreased mRNA levels for osteoblast marker genes, Osx, Col1a1 and Alp without any change in osteoclast marker genes. Etanercept increased Osx, Alp, and Ocn in both WT and FcγRIIb-/- mice. Osteoclast marker genes including TNF-α, Trap and RANKL/OPG ratio was decreased in WT. Serum markers of proinflammatory cytokines, TNF-α, IFNγ, IL-6, and IL-17A, were increased in FcγRIIb-/- mice and etanercept antagonized these effects in FcγRIIb-/- mice. Etanercept increased serum PTH levels in the FcγRIIb-/- mouse model of lupus. Our results suggest that deletion of FcγRIIb induces osteopenia by increasing the level of proinflammatory cytokines. Etanercept is effective in preventing mandibular bone loss in FcγRIIb-/- mice, suggesting that anti-TNF-α therapy may be able to ameliorate mandibular bone loss in SLE patients with periodontitis.Nithidol SakunrangsitPiyanuch MetheepakornchaiSarinya KumpunyaMatthew Blake GreenblattAsada LeelahavanichkulPrapaporn PisitkunSutada LotinunPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 4, p e0250215 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nithidol Sakunrangsit Piyanuch Metheepakornchai Sarinya Kumpunya Matthew Blake Greenblatt Asada Leelahavanichkul Prapaporn Pisitkun Sutada Lotinun Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
description	Patients with systemic lupus erythematosus are at increased risk for alveolar bone loss due to periodontitis possibly as a result of a pathogenic immune response to oral bacteria and inflammation. The aim of the present study was to investigate whether an anti-TNF-α antagonist could prevent mandibular bone loss in the FcγRIIb-/- mouse model of lupus. Mice lacking FcγRIIb had decreased cancellous and cortical bone volume at 6 months of age. Etanercept increased cancellous but not cortical bone volume in WT and increased both cancellous bone volume and cortical thickness in FcγRIIb-deficient mice. FcγRIIb deficiency decreased mRNA levels for osteoblast marker genes, Osx, Col1a1 and Alp without any change in osteoclast marker genes. Etanercept increased Osx, Alp, and Ocn in both WT and FcγRIIb-/- mice. Osteoclast marker genes including TNF-α, Trap and RANKL/OPG ratio was decreased in WT. Serum markers of proinflammatory cytokines, TNF-α, IFNγ, IL-6, and IL-17A, were increased in FcγRIIb-/- mice and etanercept antagonized these effects in FcγRIIb-/- mice. Etanercept increased serum PTH levels in the FcγRIIb-/- mouse model of lupus. Our results suggest that deletion of FcγRIIb induces osteopenia by increasing the level of proinflammatory cytokines. Etanercept is effective in preventing mandibular bone loss in FcγRIIb-/- mice, suggesting that anti-TNF-α therapy may be able to ameliorate mandibular bone loss in SLE patients with periodontitis.
format	article
author	Nithidol Sakunrangsit Piyanuch Metheepakornchai Sarinya Kumpunya Matthew Blake Greenblatt Asada Leelahavanichkul Prapaporn Pisitkun Sutada Lotinun
author_facet	Nithidol Sakunrangsit Piyanuch Metheepakornchai Sarinya Kumpunya Matthew Blake Greenblatt Asada Leelahavanichkul Prapaporn Pisitkun Sutada Lotinun
author_sort	Nithidol Sakunrangsit
title	Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
title_short	Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
title_full	Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
title_fullStr	Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
title_full_unstemmed	Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.
title_sort	etanercept prevents tnf-α mediated mandibular bone loss in fcγriib-/- lupus model.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/884279d1b9c24f5fa2f526bb2db3d737
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Etanercept prevents TNF-α mediated mandibular bone loss in FcγRIIb-/- lupus model.

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