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Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells

BACKGROUND: Chondrogenesis is the complex process that leads to the establishment of cartilage and bone formation. Due to their ability to differentiate in vitro and mimic development, embryonic stem cells (ESCs) show great potential for investigating developmental processes. In this study, we used...

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Autores principales: Yamashita, Akihiro, Nishikawa, Sandi, Rancourt, Derrick E.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881868/
https://www.ncbi.nlm.nih.gov/pubmed/20539759
http://dx.doi.org/10.1371/journal.pone.0010998
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author Yamashita, Akihiro
Nishikawa, Sandi
Rancourt, Derrick E.
author_facet Yamashita, Akihiro
Nishikawa, Sandi
Rancourt, Derrick E.
author_sort Yamashita, Akihiro
collection PubMed
description BACKGROUND: Chondrogenesis is the complex process that leads to the establishment of cartilage and bone formation. Due to their ability to differentiate in vitro and mimic development, embryonic stem cells (ESCs) show great potential for investigating developmental processes. In this study, we used chondrogenic differentiation of ESCs as a model to analyze morphogenetic events during chondrogenesis. METHODOLOGY/PRINCIPAL FINDINGS: ESCs were differentiated into the chondrocyte lineage, forming small cartilaginous aggregates in suspension. Differentiated ESCs showed that chondrogenesis was typically characterized by five overlapping stages. During the first stage, cell condensation and aggregate formation was observed. The second stage was characterized by differentiation into chondrocytes and fibril scaffold formation within spherical aggregates. Deposition of cartilaginous extracellular matrix and cartilage formation were hallmarks of the third stage. Apoptosis of chondrocytes, hypertrophy and/or degradation of cartilage occurred during the fourth stage. Finally, during the fifth stage, bone replacement with membranous calcified tissues took place. CONCLUSIONS/SIGNIFICANCE: We demonstrate that ESCs show the chondrogenic differentiation pathway from the pluripotent stem cell to terminal skeletogenesis through these five stages in vitro. During each stage, morphological changes acquired in preceding stages played an important role in further development as a scaffold or template in subsequent stages. The study of chondrogenesis via ESC differentiation may be informative to our further understanding of skeletal growth and regeneration.
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spelling pubmed-28818682010-06-10 Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells Yamashita, Akihiro Nishikawa, Sandi Rancourt, Derrick E. PLoS One Research Article BACKGROUND: Chondrogenesis is the complex process that leads to the establishment of cartilage and bone formation. Due to their ability to differentiate in vitro and mimic development, embryonic stem cells (ESCs) show great potential for investigating developmental processes. In this study, we used chondrogenic differentiation of ESCs as a model to analyze morphogenetic events during chondrogenesis. METHODOLOGY/PRINCIPAL FINDINGS: ESCs were differentiated into the chondrocyte lineage, forming small cartilaginous aggregates in suspension. Differentiated ESCs showed that chondrogenesis was typically characterized by five overlapping stages. During the first stage, cell condensation and aggregate formation was observed. The second stage was characterized by differentiation into chondrocytes and fibril scaffold formation within spherical aggregates. Deposition of cartilaginous extracellular matrix and cartilage formation were hallmarks of the third stage. Apoptosis of chondrocytes, hypertrophy and/or degradation of cartilage occurred during the fourth stage. Finally, during the fifth stage, bone replacement with membranous calcified tissues took place. CONCLUSIONS/SIGNIFICANCE: We demonstrate that ESCs show the chondrogenic differentiation pathway from the pluripotent stem cell to terminal skeletogenesis through these five stages in vitro. During each stage, morphological changes acquired in preceding stages played an important role in further development as a scaffold or template in subsequent stages. The study of chondrogenesis via ESC differentiation may be informative to our further understanding of skeletal growth and regeneration. Public Library of Science 2010-06-07 /pmc/articles/PMC2881868/ /pubmed/20539759 http://dx.doi.org/10.1371/journal.pone.0010998 Text en Yamashita et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yamashita, Akihiro
Nishikawa, Sandi
Rancourt, Derrick E.
Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells
title Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells
title_full Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells
title_fullStr Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells
title_full_unstemmed Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells
title_short Identification of Five Developmental Processes during Chondrogenic Differentiation of Embryonic Stem Cells
title_sort identification of five developmental processes during chondrogenic differentiation of embryonic stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2881868/
https://www.ncbi.nlm.nih.gov/pubmed/20539759
http://dx.doi.org/10.1371/journal.pone.0010998
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