Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing

Abstract Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation...

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Autores principales: S. Lee, L. H. Remark, A. M. Josephson, K. Leclerc, E. Muiños Lopez, D. J. Kirby, Devan Mehta, H. P. Litwa, M. Z. Wong, S. Y. Shin, P. Leucht
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/55b9dc63f311407686bfdaea83e4efd5
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spelling oai:doaj.org-article:55b9dc63f311407686bfdaea83e4efd52021-12-02T15:00:39ZNotch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing10.1038/s41536-021-00139-x2057-3995https://doaj.org/article/55b9dc63f311407686bfdaea83e4efd52021-05-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00139-xhttps://doaj.org/toc/2057-3995Abstract Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.S. LeeL. H. RemarkA. M. JosephsonK. LeclercE. Muiños LopezD. J. KirbyDevan MehtaH. P. LitwaM. Z. WongS. Y. ShinP. LeuchtNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
spellingShingle Medicine
R
S. Lee
L. H. Remark
A. M. Josephson
K. Leclerc
E. Muiños Lopez
D. J. Kirby
Devan Mehta
H. P. Litwa
M. Z. Wong
S. Y. Shin
P. Leucht
Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
description Abstract Adult bone regeneration is orchestrated by the precise actions of osteoprogenitor cells (OPCs). However, the mechanisms by which OPC proliferation and differentiation are linked and thereby regulated are yet to be defined. Here, we present evidence that during intramembranous bone formation OPC proliferation is controlled by Notch signaling, while differentiation is initiated by activation of canonical Wnt signaling. The temporospatial separation of Notch and Wnt signal activation during the early stages of bone regeneration suggests crosstalk between the two pathways. In vitro and in vivo manipulation of the two essential pathways demonstrate that Wnt activation leads to initiation of osteogenic differentiation and at the same time inhibits Notch signaling, which results in termination of the proliferative phase. Here, we establish canonical Wnt signaling as a key regulator that facilitates the crosstalk between OPC proliferation and differentiation during intramembranous, primary bone healing.
format article
author S. Lee
L. H. Remark
A. M. Josephson
K. Leclerc
E. Muiños Lopez
D. J. Kirby
Devan Mehta
H. P. Litwa
M. Z. Wong
S. Y. Shin
P. Leucht
author_facet S. Lee
L. H. Remark
A. M. Josephson
K. Leclerc
E. Muiños Lopez
D. J. Kirby
Devan Mehta
H. P. Litwa
M. Z. Wong
S. Y. Shin
P. Leucht
author_sort S. Lee
title Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
title_short Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
title_full Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
title_fullStr Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
title_full_unstemmed Notch-Wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
title_sort notch-wnt signal crosstalk regulates proliferation and differentiation of osteoprogenitor cells during intramembranous bone healing
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/55b9dc63f311407686bfdaea83e4efd5
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