Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells

Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an at...

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Autores principales: Akbulut, Asim Cengiz, Wasilewski, Grzegorz B., Rapp, Nikolas, Forin, Francesco, Singer, Heike, Czogalla-Nitsche, Katrin J., Schurgers, Leon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876270/
https://www.ncbi.nlm.nih.gov/pubmed/33585456
http://dx.doi.org/10.3389/fcell.2020.618760
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author Akbulut, Asim Cengiz
Wasilewski, Grzegorz B.
Rapp, Nikolas
Forin, Francesco
Singer, Heike
Czogalla-Nitsche, Katrin J.
Schurgers, Leon J.
author_facet Akbulut, Asim Cengiz
Wasilewski, Grzegorz B.
Rapp, Nikolas
Forin, Francesco
Singer, Heike
Czogalla-Nitsche, Katrin J.
Schurgers, Leon J.
author_sort Akbulut, Asim Cengiz
collection PubMed
description Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation.
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spelling pubmed-78762702021-02-12 Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells Akbulut, Asim Cengiz Wasilewski, Grzegorz B. Rapp, Nikolas Forin, Francesco Singer, Heike Czogalla-Nitsche, Katrin J. Schurgers, Leon J. Front Cell Dev Biol Cell and Developmental Biology Development of clinical stem cell interventions are hampered by immature cell progeny under current protocols. Human mesenchymal stem cells (hMSCs) are characterized by their ability to self-renew and differentiate into multiple lineages. Generating hMSCs from pluripotent stem cells (iPSCs) is an attractive avenue for cost-efficient and scalable production of cellular material. In this study we generate mature osteoblasts from iPSCs using a stable expandable MSC intermediate, refining established protocols. We investigated the timeframe and phenotype of cells under osteogenic conditions as well as the effect of menaquinone-7 (MK-7) on differentiation. From day 2 we noted a significant increase in RUNX2 expression under osteogenic conditions with MK-7, as well as decreases in ROS species production, increased cellular migration and changes to dynamics of collagen deposition when compared to differentiated cells that were not treated with MK-7. At day 21 OsteoMK-7 increased alkaline phosphatase activity and collagen deposition, as well as downregulated RUNX2 expression, suggesting to a mature cellular phenotype. Throughout we note no changes to expression of osteocalcin suggesting a non-canonical function of MK-7 in osteoblast differentiation. Together our data provide further mechanistic insight between basic and clinical studies on extrahepatic activity of MK-7. Our findings show that MK-7 promotes osteoblast maturation thereby increasing osteogenic differentiation. Frontiers Media S.A. 2021-01-28 /pmc/articles/PMC7876270/ /pubmed/33585456 http://dx.doi.org/10.3389/fcell.2020.618760 Text en Copyright © 2021 Akbulut, Wasilewski, Rapp, Forin, Singer, Czogalla-Nitsche and Schurgers. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Akbulut, Asim Cengiz
Wasilewski, Grzegorz B.
Rapp, Nikolas
Forin, Francesco
Singer, Heike
Czogalla-Nitsche, Katrin J.
Schurgers, Leon J.
Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
title Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
title_full Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
title_fullStr Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
title_full_unstemmed Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
title_short Menaquinone-7 Supplementation Improves Osteogenesis in Pluripotent Stem Cell Derived Mesenchymal Stem Cells
title_sort menaquinone-7 supplementation improves osteogenesis in pluripotent stem cell derived mesenchymal stem cells
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876270/
https://www.ncbi.nlm.nih.gov/pubmed/33585456
http://dx.doi.org/10.3389/fcell.2020.618760
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