Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton

Abstract Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimu...

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Autores principales:	Sade W. Clayton, Ga I. Ban, Cunren Liu, Rosa Serra
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e00628fa27cf4f279488dc78fa5d23a1
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spelling	oai:doaj.org-article:e00628fa27cf4f279488dc78fa5d23a12021-12-02T15:10:18ZCanonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton10.1038/s41598-020-78206-42045-2322https://doaj.org/article/e00628fa27cf4f279488dc78fa5d23a12020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78206-4https://doaj.org/toc/2045-2322Abstract Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimulated expression of Scleraxis mRNA by 2 h and Fibromodulin and Adamtsl2 mRNAs by 8 h of treatment. Regulation of Scleraxis by TGF-β did not require new protein synthesis; however, protein synthesis was required for expression of Fibromodulin and Adamtsl2 indicating the necessity of an intermediate. We subsequently showed Scleraxis was a potential intermediate for TGF-β-regulated expression of Fibromodulin and Adamtsl2. The canonical effector Smad3 was not necessary for TGF-β-mediated regulation of Scleraxis. Smad3 was necessary for regulation of Fibromodulin and Adamtsl2, but not sufficient to super-induce expression with TGF-β treatment. Next, the role of several noncanonical TGF-β pathways were tested. We found that ERK1/2 was activated by TGF-β and required to regulate expression of Scleraxis, Fibromodulin, and Adamtsl2. Based on these results, we propose a model in which TGF-β regulates Scleraxis via ERK1/2 and then Scleraxis and Smad3 cooperate to regulate Fibromodulin and Adamtsl2. These results define a novel signaling mechanism for TGFβ-mediated fibrous differentiation in sclerotome.Sade W. ClaytonGa I. BanCunren LiuRosa SerraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sade W. Clayton Ga I. Ban Cunren Liu Rosa Serra Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
description	Abstract Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimulated expression of Scleraxis mRNA by 2 h and Fibromodulin and Adamtsl2 mRNAs by 8 h of treatment. Regulation of Scleraxis by TGF-β did not require new protein synthesis; however, protein synthesis was required for expression of Fibromodulin and Adamtsl2 indicating the necessity of an intermediate. We subsequently showed Scleraxis was a potential intermediate for TGF-β-regulated expression of Fibromodulin and Adamtsl2. The canonical effector Smad3 was not necessary for TGF-β-mediated regulation of Scleraxis. Smad3 was necessary for regulation of Fibromodulin and Adamtsl2, but not sufficient to super-induce expression with TGF-β treatment. Next, the role of several noncanonical TGF-β pathways were tested. We found that ERK1/2 was activated by TGF-β and required to regulate expression of Scleraxis, Fibromodulin, and Adamtsl2. Based on these results, we propose a model in which TGF-β regulates Scleraxis via ERK1/2 and then Scleraxis and Smad3 cooperate to regulate Fibromodulin and Adamtsl2. These results define a novel signaling mechanism for TGFβ-mediated fibrous differentiation in sclerotome.
format	article
author	Sade W. Clayton Ga I. Ban Cunren Liu Rosa Serra
author_facet	Sade W. Clayton Ga I. Ban Cunren Liu Rosa Serra
author_sort	Sade W. Clayton
title	Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
title_short	Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
title_full	Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
title_fullStr	Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
title_full_unstemmed	Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
title_sort	canonical and noncanonical tgf-β signaling regulate fibrous tissue differentiation in the axial skeleton
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/e00628fa27cf4f279488dc78fa5d23a1
work_keys_str_mv	AT sadewclayton canonicalandnoncanonicaltgfbsignalingregulatefibroustissuedifferentiationintheaxialskeleton AT gaiban canonicalandnoncanonicaltgfbsignalingregulatefibroustissuedifferentiationintheaxialskeleton AT cunrenliu canonicalandnoncanonicaltgfbsignalingregulatefibroustissuedifferentiationintheaxialskeleton AT rosaserra canonicalandnoncanonicaltgfbsignalingregulatefibroustissuedifferentiationintheaxialskeleton
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Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton

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