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

menaquinone-7 mesenchymal stem cells osteogenesis pluripotent stem cells vitamin K

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2020
Historique:
received: 18 10 2020
accepted: 09 12 2020
entrez: 15 2 2021
pubmed: 16 2 2021
medline: 16 2 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33585456
doi: 10.3389/fcell.2020.618760
pmc: PMC7876270
doi:

Types de publication

Journal Article

Langues

eng

Pagination

618760

Informations de copyright

Copyright © 2021 Akbulut, Wasilewski, Rapp, Forin, Singer, Czogalla-Nitsche and Schurgers.

Déclaration de conflit d'intérêts

LS reports financial support from Boehringer Ingelheim, Daichi Sankyo, Bayer, Nattopharma, and Immunodiagnostic systems (IDS), outside the submitted work. GW was employed by Nattopharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Asim Cengiz Akbulut (AC)

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.

Grzegorz B Wasilewski (GB)

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
NattoPharma ASA, Oslo, Norway.

Nikolas Rapp (N)

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.

Francesco Forin (F)

Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.

Heike Singer (H)

Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.

Katrin J Czogalla-Nitsche (KJ)

Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.

Leon J Schurgers (LJ)

Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Department of Nephro-Cardiology, Rheinisch-Westfälische Technische Hochschule Klinikum, Aachen, Germany.

Classifications MeSH