Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation

Abstract Targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteob...

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Autores principales:	Mona Elsafadi, Tasneem Shinwari, Sami Al-Malki, Muthurangan Manikandan, Amer Mahmood, Abdullah Aldahmash, Musaad Alfayez, Moustapha Kassem, Nehad M. Alajez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb6935809e8348cd90ae99947c72db94
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spelling	oai:doaj.org-article:eb6935809e8348cd90ae99947c72db942021-12-02T16:08:44ZConvergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation10.1038/s41598-019-41543-02045-2322https://doaj.org/article/eb6935809e8348cd90ae99947c72db942019-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-41543-0https://doaj.org/toc/2045-2322Abstract Targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting opposite in vivo phenotypes, namely, bone forming (hBMSC+bone) and non-bone forming (hBMSC−Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC−Bone cells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMP signaling in those cells. Concordantly, activation of TGFβ signaling in hBMSC−Bone cells using either recombinant TGFβ1 protein or knockdown of SERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 or via siRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC−Bone cells. Concordantly, recombinant NOG impaired ex vivo osteoblastic differentiation of hBMSC+Bone cells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between TGFB and BMP signaling that regulates hBMSC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMSCs for clinical applications.Mona ElsafadiTasneem ShinwariSami Al-MalkiMuthurangan ManikandanAmer MahmoodAbdullah AldahmashMusaad AlfayezMoustapha KassemNehad M. AlajezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mona Elsafadi Tasneem Shinwari Sami Al-Malki Muthurangan Manikandan Amer Mahmood Abdullah Aldahmash Musaad Alfayez Moustapha Kassem Nehad M. Alajez Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
description	Abstract Targeting regulatory signaling pathways that control human bone marrow stromal (skeletal or mesenchymal) stem cell (hBMSC) differentiation and lineage fate determination is gaining momentum in the regenerative medicine field. Therefore, to identify the central regulatory mechanism of osteoblast differentiation of hBMSCs, the molecular phenotypes of two clonal hBMSC lines exhibiting opposite in vivo phenotypes, namely, bone forming (hBMSC+bone) and non-bone forming (hBMSC−Bone) cells, were studied. Global transcriptome analysis revealed significant downregulation of several TGFβ responsive genes, namely, TAGLN, TMP1, ACTA2, TGFβ2, SMAD6, SMAD9, BMP2, and BMP4 in hBMSC−Bone cells and upregulation on SERPINB2 and NOG. Transcriptomic data was associated with marked reduction in SMAD2 protein phosphorylation, which thereby implies the inactivation of TGFβ and BMP signaling in those cells. Concordantly, activation of TGFβ signaling in hBMSC−Bone cells using either recombinant TGFβ1 protein or knockdown of SERPINB2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 or via siRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC−Bone cells. Concordantly, recombinant NOG impaired ex vivo osteoblastic differentiation of hBMSC+Bone cells, which was associated with SERBINB2 upregulation. Our data suggests the existence of reciprocal relationship between TGFB and BMP signaling that regulates hBMSC lineage commitment and differentiation, whilst provide a plausible strategy for generating osteoblastic committed cells from hBMSCs for clinical applications.
format	article
author	Mona Elsafadi Tasneem Shinwari Sami Al-Malki Muthurangan Manikandan Amer Mahmood Abdullah Aldahmash Musaad Alfayez Moustapha Kassem Nehad M. Alajez
author_facet	Mona Elsafadi Tasneem Shinwari Sami Al-Malki Muthurangan Manikandan Amer Mahmood Abdullah Aldahmash Musaad Alfayez Moustapha Kassem Nehad M. Alajez
author_sort	Mona Elsafadi
title	Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
title_short	Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
title_full	Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
title_fullStr	Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
title_full_unstemmed	Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
title_sort	convergence of tgfβ and bmp signaling in regulating human bone marrow stromal cell differentiation
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/eb6935809e8348cd90ae99947c72db94
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Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation

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