Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.

Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains t...

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Autores principales: Teruyo Oishi, Akiyoshi Uezumi, Arihiko Kanaji, Naoki Yamamoto, Asami Yamaguchi, Harumoto Yamada, Kunihiro Tsuchida
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spelling oai:doaj.org-article:2ea087da67bb4b90801170583efd809b2021-11-18T07:57:25ZOsteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.1932-620310.1371/journal.pone.0056641https://doaj.org/article/2ea087da67bb4b90801170583efd809b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23457598/?tool=EBIhttps://doaj.org/toc/1932-6203Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+) and PDGFRα(+) cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+) cells and PDGFRα(+) cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+) cells formed bone-like tissue and showed successful engraftment, while CD56(+) cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+) cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs) are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+) cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+) cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+) cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+) cells. Our results suggest that PDGFRα(+) cells may be the major source of HO and that the newly identified miRNAs may regulate osteogenic differentiation process of PDGFRα(+) cells.Teruyo OishiAkiyoshi UezumiArihiko KanajiNaoki YamamotoAsami YamaguchiHarumoto YamadaKunihiro TsuchidaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56641 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Teruyo Oishi
Akiyoshi Uezumi
Arihiko Kanaji
Naoki Yamamoto
Asami Yamaguchi
Harumoto Yamada
Kunihiro Tsuchida
Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
description Heterotopic ossification (HO) is defined as the formation of ectopic bone in soft tissue outside the skeletal tissue. HO is thought to result from aberrant differentiation of osteogenic progenitors within skeletal muscle. However, the precise origin of HO is still unclear. Skeletal muscle contains two kinds of progenitor cells, myogenic progenitors and mesenchymal progenitors. Myogenic and mesenchymal progenitors in human skeletal muscle can be identified as CD56(+) and PDGFRα(+) cells, respectively. The purpose of this study was to investigate the osteogenic differentiation potential of human skeletal muscle-derived progenitors. Both CD56(+) cells and PDGFRα(+) cells showed comparable osteogenic differentiation potential in vitro. However, in an in vivo ectopic bone formation model, PDGFRα(+) cells formed bone-like tissue and showed successful engraftment, while CD56(+) cells did not form bone-like tissue and did not adapt to an osteogenic environment. Immunohistological analysis of human HO sample revealed that many PDGFRα(+) cells were localized in proximity to ectopic bone formed in skeletal muscle. MicroRNAs (miRNAs) are known to regulate many biological processes including osteogenic differentiation. We investigated the participation of miRNAs in the osteogenic differentiation of PDGFRα(+) cells by using microarray. We identified miRNAs that had not been known to be involved in osteogenesis but showed dramatic changes during osteogenic differentiation of PDGFRα(+) cells. Upregulation of miR-146b-5p and -424 and downregulation of miR-7 during osteogenic differentiation of PDGFRα(+) cells were confirmed by quantitative real-time RT-PCR. Inhibition of upregulated miRNAs, miR-146b-5p and -424, resulted in the suppression of osteocyte maturation, suggesting that these two miRNAs have the positive role in the osteogenesis of PDGFRα(+) cells. Our results suggest that PDGFRα(+) cells may be the major source of HO and that the newly identified miRNAs may regulate osteogenic differentiation process of PDGFRα(+) cells.
format article
author Teruyo Oishi
Akiyoshi Uezumi
Arihiko Kanaji
Naoki Yamamoto
Asami Yamaguchi
Harumoto Yamada
Kunihiro Tsuchida
author_facet Teruyo Oishi
Akiyoshi Uezumi
Arihiko Kanaji
Naoki Yamamoto
Asami Yamaguchi
Harumoto Yamada
Kunihiro Tsuchida
author_sort Teruyo Oishi
title Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
title_short Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
title_full Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
title_fullStr Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
title_full_unstemmed Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
title_sort osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/2ea087da67bb4b90801170583efd809b
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AT akiyoshiuezumi osteogenicdifferentiationcapacityofhumanskeletalmusclederivedprogenitorcells
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AT naokiyamamoto osteogenicdifferentiationcapacityofhumanskeletalmusclederivedprogenitorcells
AT asamiyamaguchi osteogenicdifferentiationcapacityofhumanskeletalmusclederivedprogenitorcells
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