Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis

Graphene is capable of promoting osteogenesis without chemical induction. Nevertheless, the underlying mechanism(s) remain largely unknown. The objectives here were: (i) to assess whether graphene scaffolds are capable of supporting osteogenesis in vivo and; (ii) to ascertain the participation of th...

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Autores principales: Xie, Han, Cao, Tong, Franco-Obregón, Alfredo, Rosa, Vinicius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387117/
https://www.ncbi.nlm.nih.gov/pubmed/30699966
http://dx.doi.org/10.3390/ijms20030574
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author Xie, Han
Cao, Tong
Franco-Obregón, Alfredo
Rosa, Vinicius
author_facet Xie, Han
Cao, Tong
Franco-Obregón, Alfredo
Rosa, Vinicius
author_sort Xie, Han
collection PubMed
description Graphene is capable of promoting osteogenesis without chemical induction. Nevertheless, the underlying mechanism(s) remain largely unknown. The objectives here were: (i) to assess whether graphene scaffolds are capable of supporting osteogenesis in vivo and; (ii) to ascertain the participation of the integrin/FAK mechanotransduction axis during the osteogenic differentiation induced by graphene. MSC-impregnated graphene scaffolds (n = 6) were implanted into immunocompromised mice (28 days). Alternatively, MSCs were seeded onto PDMS substrates (modulus of elasticity = 130, 830 and 1300 kPa) coated with a single monomolecular layer of graphene and cultured in basal medium (10 days). The ensuing expressions of FAK-p397, integrin, ROCK1, F-actin, Smad p1/5, RUNX2, OCN and OPN were evaluated by Western blot (n = 3). As controls, MSCs were plated onto uncoated PDMS in the presence of mechanotransduction inhibitors (echistatin, Y27632 and DMH1). MSC-impregnated graphene scaffolds exhibited positive immunoexpression of bone-related markers (RUNX2 and OPN) without the assistance of osteogenic inducers. In vitro, regardless of the stiffness of the underlying PDMS substrate, MSCs seeded onto graphene-coated PDMS substrates demonstrated higher expressions of all tested osteogenic and integrin/FAK proteins tested compared to MSCs seeded onto PDMS alone. Hence, graphene promotes osteogenesis via the activation of the mechanosensitive integrin/FAK axis.
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spelling pubmed-63871172019-02-27 Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis Xie, Han Cao, Tong Franco-Obregón, Alfredo Rosa, Vinicius Int J Mol Sci Article Graphene is capable of promoting osteogenesis without chemical induction. Nevertheless, the underlying mechanism(s) remain largely unknown. The objectives here were: (i) to assess whether graphene scaffolds are capable of supporting osteogenesis in vivo and; (ii) to ascertain the participation of the integrin/FAK mechanotransduction axis during the osteogenic differentiation induced by graphene. MSC-impregnated graphene scaffolds (n = 6) were implanted into immunocompromised mice (28 days). Alternatively, MSCs were seeded onto PDMS substrates (modulus of elasticity = 130, 830 and 1300 kPa) coated with a single monomolecular layer of graphene and cultured in basal medium (10 days). The ensuing expressions of FAK-p397, integrin, ROCK1, F-actin, Smad p1/5, RUNX2, OCN and OPN were evaluated by Western blot (n = 3). As controls, MSCs were plated onto uncoated PDMS in the presence of mechanotransduction inhibitors (echistatin, Y27632 and DMH1). MSC-impregnated graphene scaffolds exhibited positive immunoexpression of bone-related markers (RUNX2 and OPN) without the assistance of osteogenic inducers. In vitro, regardless of the stiffness of the underlying PDMS substrate, MSCs seeded onto graphene-coated PDMS substrates demonstrated higher expressions of all tested osteogenic and integrin/FAK proteins tested compared to MSCs seeded onto PDMS alone. Hence, graphene promotes osteogenesis via the activation of the mechanosensitive integrin/FAK axis. MDPI 2019-01-29 /pmc/articles/PMC6387117/ /pubmed/30699966 http://dx.doi.org/10.3390/ijms20030574 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xie, Han
Cao, Tong
Franco-Obregón, Alfredo
Rosa, Vinicius
Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis
title Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis
title_full Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis
title_fullStr Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis
title_full_unstemmed Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis
title_short Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis
title_sort graphene-induced osteogenic differentiation is mediated by the integrin/fak axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387117/
https://www.ncbi.nlm.nih.gov/pubmed/30699966
http://dx.doi.org/10.3390/ijms20030574
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AT francoobregonalfredo grapheneinducedosteogenicdifferentiationismediatedbytheintegrinfakaxis
AT rosavinicius grapheneinducedosteogenicdifferentiationismediatedbytheintegrinfakaxis