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

journal contribution
submitted on 2024-05-26, 06:44 and posted on 2024-05-27, 04:47 authored by Mona Elsafadi, Tasneem Shinwari, Sami Al-Malki, Muthurangan Manikandan, Amer Mahmood, Abdullah Aldahmash, Musaad Alfayez, Moustapha Kassem, Nehad M. Alajez

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.

Author Correction: Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation: https://dx.doi.org/10.1038/s41598-019-54821-8, published online 25 November 2019.

Other Information

Published in: Scientific Reports
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://doi.org/10.1038/s41598-019-41543-0

Funding

Open Access funding provided by the Qatar National Library.

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2019

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • College of Health and Life Sciences - HBKU

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