Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice

Abstract Patients with systemic lupus erythematosus (SLE) have increased inflammatory cytokines, leading to periodontitis and alveolar bone loss. However, the mechanisms driving this phenomenon are still unknown. Here, we have identified novel therapeutic targets for and mediators of lupus-mediated...

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Autores principales:	Nithidol Sakunrangsit, Jatuphol Pholtaisong, Jeerus Sucharitakul, Sasithorn Wanna-udom, Pinidphon Prombutara, Prapaporn Pisitkun, Asada Leelahavanichkul, Chatchawit Aporntewan, Matthew B. Greenblatt, Sutada Lotinun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7183a4525094c00bb9a4d81e87fe27c
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spelling	oai:doaj.org-article:f7183a4525094c00bb9a4d81e87fe27c2021-12-02T18:14:30ZIdentification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice10.1038/s41598-021-98108-32045-2322https://doaj.org/article/f7183a4525094c00bb9a4d81e87fe27c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98108-3https://doaj.org/toc/2045-2322Abstract Patients with systemic lupus erythematosus (SLE) have increased inflammatory cytokines, leading to periodontitis and alveolar bone loss. However, the mechanisms driving this phenomenon are still unknown. Here, we have identified novel therapeutic targets for and mediators of lupus-mediated bone loss using RNA-sequencing (RNA-seq) in a FcγRIIB -/- mouse model of lupus associated osteopenia. A total of 2,710 upregulated and 3,252 downregulated DEGs were identified. The GO and KEGG annotations revealed that osteoclast differentiation, bone mineralization, ossification, and myeloid cell development were downregulated. WikiPathways indicated that Hedgehog, TNFα NF-κB and Notch signaling pathway were also decreased. We identified downregulated targets, Sufu and Serpina12, that have important roles in bone homeostasis. Sufu and Serpina12 were related to Hedgehog signaling proteins, including Gli1, Gli2, Gli3, Ptch1, and Ptch2. Gene knockdown analysis demonstrated that Sufu, and Serpina12 contributed to osteoclastogenesis and osteoblastogenesis, respectively. Osteoclast and osteoblast marker genes were significantly decreased in Sufu-deficient and Serpina12-deficient cells, respectively. Our results suggest that alterations in Hedgehog signaling play an important role in the pathogenesis of osteopenia in FcγRIIB -/- mice. The novel DEGs and pathways identified in this study provide new insight into the underlying mechanisms of mandibular bone loss during lupus development.Nithidol SakunrangsitJatuphol PholtaisongJeerus SucharitakulSasithorn Wanna-udomPinidphon PrombutaraPrapaporn PisitkunAsada LeelahavanichkulChatchawit AporntewanMatthew B. GreenblattSutada LotinunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nithidol Sakunrangsit Jatuphol Pholtaisong Jeerus Sucharitakul Sasithorn Wanna-udom Pinidphon Prombutara Prapaporn Pisitkun Asada Leelahavanichkul Chatchawit Aporntewan Matthew B. Greenblatt Sutada Lotinun Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice
description	Abstract Patients with systemic lupus erythematosus (SLE) have increased inflammatory cytokines, leading to periodontitis and alveolar bone loss. However, the mechanisms driving this phenomenon are still unknown. Here, we have identified novel therapeutic targets for and mediators of lupus-mediated bone loss using RNA-sequencing (RNA-seq) in a FcγRIIB -/- mouse model of lupus associated osteopenia. A total of 2,710 upregulated and 3,252 downregulated DEGs were identified. The GO and KEGG annotations revealed that osteoclast differentiation, bone mineralization, ossification, and myeloid cell development were downregulated. WikiPathways indicated that Hedgehog, TNFα NF-κB and Notch signaling pathway were also decreased. We identified downregulated targets, Sufu and Serpina12, that have important roles in bone homeostasis. Sufu and Serpina12 were related to Hedgehog signaling proteins, including Gli1, Gli2, Gli3, Ptch1, and Ptch2. Gene knockdown analysis demonstrated that Sufu, and Serpina12 contributed to osteoclastogenesis and osteoblastogenesis, respectively. Osteoclast and osteoblast marker genes were significantly decreased in Sufu-deficient and Serpina12-deficient cells, respectively. Our results suggest that alterations in Hedgehog signaling play an important role in the pathogenesis of osteopenia in FcγRIIB -/- mice. The novel DEGs and pathways identified in this study provide new insight into the underlying mechanisms of mandibular bone loss during lupus development.
format	article
author	Nithidol Sakunrangsit Jatuphol Pholtaisong Jeerus Sucharitakul Sasithorn Wanna-udom Pinidphon Prombutara Prapaporn Pisitkun Asada Leelahavanichkul Chatchawit Aporntewan Matthew B. Greenblatt Sutada Lotinun
author_facet	Nithidol Sakunrangsit Jatuphol Pholtaisong Jeerus Sucharitakul Sasithorn Wanna-udom Pinidphon Prombutara Prapaporn Pisitkun Asada Leelahavanichkul Chatchawit Aporntewan Matthew B. Greenblatt Sutada Lotinun
author_sort	Nithidol Sakunrangsit
title	Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice
title_short	Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice
title_full	Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice
title_fullStr	Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice
title_full_unstemmed	Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice
title_sort	identification of candidate regulators of mandibular bone loss in fcγriib -/- mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f7183a4525094c00bb9a4d81e87fe27c
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Identification of candidate regulators of mandibular bone loss in FcγRIIB -/- Mice

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