Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation
<p dir="ltr">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...
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| مؤلفون آخرون: | , , , , , , , |
| منشور في: |
2019
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| الملخص: | <p dir="ltr">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 <i>in vivo</i> phenotypes, namely, bone forming (hBMSC<sup>+bone</sup>) and non-bone forming (hBMSC<sup>−Bone</sup>) 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<sup>−Bone</sup> 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<sup>−Bone</sup> cells using either recombinant TGFβ1 protein or knockdown of <i>SERPINB</i>2 TGFβ-responsive gene partially restored their osteoblastic differentiation potential. Similarly, the activation of BMP signaling using exogenous BMP4 or <i>via</i> siRNA-mediated knockdown of NOG partially restored the differentiation phenotype of hBMSC<sup>−Bone</sup> cells. Concordantly, recombinant NOG impaired <i>ex vivo</i> osteoblastic differentiation of hBMSC<sup>+Bone</sup> 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.</p><p dir="ltr">Author Correction: Convergence of TGFβ and BMP signaling in regulating human bone marrow stromal cell differentiation: <a href="https://dx.doi.org/10.1038/s41598-019-54821-8" target="_blank">https://dx.doi.org/10.1038/s41598-019-54821-8</a>, published online 25 November 2019.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://doi.org/10.1038/s41598-019-41543-0" target="_blank">https://doi.org/10.1038/s41598-019-41543-0</a></p> |
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