Zbp1-positive cells are osteogenic progenitors in periodontal ligament

Abstract Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of...

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Autores principales:	Tsugumi Ueda, Tomoaki Iwayama, Kiwako Tomita, Shuji Matsumoto, Mizuho Iwashita, Phan Bhongsatiern, Hiromi Sakashita, Chiharu Fujihara, Masahide Takedachi, Shinya Murakami
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d41fef1093864a72ad0af8b66da787fa
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spelling	oai:doaj.org-article:d41fef1093864a72ad0af8b66da787fa2021-12-02T18:15:33ZZbp1-positive cells are osteogenic progenitors in periodontal ligament10.1038/s41598-021-87016-12045-2322https://doaj.org/article/d41fef1093864a72ad0af8b66da787fa2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87016-1https://doaj.org/toc/2045-2322Abstract Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of PDL progenitors using a single cell-based strategy in this study. We first devised a new protocol to isolate PDL cells from the surface of adult murine molars and established 35 new single cell-derived clones from the PDL explant. Among these clones, six clones with high (high clones, n = 3) and low (low clones, n = 3) osteogenic potential were selected. Despite a clear difference in the osteogenic potential of these clones, no significant differences in their cell morphology, progenitor cell marker expression, alkaline phosphatase activity, proliferation rate, and differentiation-related gene and protein expression were observed. RNA-seq analysis of these clones revealed that Z-DNA binding protein-1 (Zbp1) was significantly expressed in the high osteogenic clones, indicating that Zbp1 could be a possible marker and regulator of the osteogenic differentiation of PDL progenitor cells. Zbp1-positive cells were distributed sparsely throughout the PDL. In vitro Zbp1 expression in the PDL clones remained at a high level during osteogenic differentiation. The CRISPR/Cas9 mediated Zbp1 knockout in the high clones resulted in a delay in cell differentiation. On the other hand, Zbp1 overexpression in the low clones promoted cell differentiation. These findings suggested that Zbp1 marked the PDL progenitors with high osteogenic potential and promoted their osteogenic differentiation. Clarifying the mechanism of differentiation of PDL cells by Zbp1 and other factors in future studies will facilitate a better understanding of periodontal tissue homeostasis and repair, possibly leading to the development of novel therapeutic measures.Tsugumi UedaTomoaki IwayamaKiwako TomitaShuji MatsumotoMizuho IwashitaPhan BhongsatiernHiromi SakashitaChiharu FujiharaMasahide TakedachiShinya MurakamiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tsugumi Ueda Tomoaki Iwayama Kiwako Tomita Shuji Matsumoto Mizuho Iwashita Phan Bhongsatiern Hiromi Sakashita Chiharu Fujihara Masahide Takedachi Shinya Murakami Zbp1-positive cells are osteogenic progenitors in periodontal ligament
description	Abstract Periodontal ligament (PDL) possesses a stem/progenitor population to maintain the homeostasis of periodontal tissue. However, transcription factors that regulate this population have not yet been identified. Thus, we aimed to identify a molecule related to the osteogenic differentiation of PDL progenitors using a single cell-based strategy in this study. We first devised a new protocol to isolate PDL cells from the surface of adult murine molars and established 35 new single cell-derived clones from the PDL explant. Among these clones, six clones with high (high clones, n = 3) and low (low clones, n = 3) osteogenic potential were selected. Despite a clear difference in the osteogenic potential of these clones, no significant differences in their cell morphology, progenitor cell marker expression, alkaline phosphatase activity, proliferation rate, and differentiation-related gene and protein expression were observed. RNA-seq analysis of these clones revealed that Z-DNA binding protein-1 (Zbp1) was significantly expressed in the high osteogenic clones, indicating that Zbp1 could be a possible marker and regulator of the osteogenic differentiation of PDL progenitor cells. Zbp1-positive cells were distributed sparsely throughout the PDL. In vitro Zbp1 expression in the PDL clones remained at a high level during osteogenic differentiation. The CRISPR/Cas9 mediated Zbp1 knockout in the high clones resulted in a delay in cell differentiation. On the other hand, Zbp1 overexpression in the low clones promoted cell differentiation. These findings suggested that Zbp1 marked the PDL progenitors with high osteogenic potential and promoted their osteogenic differentiation. Clarifying the mechanism of differentiation of PDL cells by Zbp1 and other factors in future studies will facilitate a better understanding of periodontal tissue homeostasis and repair, possibly leading to the development of novel therapeutic measures.
format	article
author	Tsugumi Ueda Tomoaki Iwayama Kiwako Tomita Shuji Matsumoto Mizuho Iwashita Phan Bhongsatiern Hiromi Sakashita Chiharu Fujihara Masahide Takedachi Shinya Murakami
author_facet	Tsugumi Ueda Tomoaki Iwayama Kiwako Tomita Shuji Matsumoto Mizuho Iwashita Phan Bhongsatiern Hiromi Sakashita Chiharu Fujihara Masahide Takedachi Shinya Murakami
author_sort	Tsugumi Ueda
title	Zbp1-positive cells are osteogenic progenitors in periodontal ligament
title_short	Zbp1-positive cells are osteogenic progenitors in periodontal ligament
title_full	Zbp1-positive cells are osteogenic progenitors in periodontal ligament
title_fullStr	Zbp1-positive cells are osteogenic progenitors in periodontal ligament
title_full_unstemmed	Zbp1-positive cells are osteogenic progenitors in periodontal ligament
title_sort	zbp1-positive cells are osteogenic progenitors in periodontal ligament
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d41fef1093864a72ad0af8b66da787fa
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_version_	1718378363079360512

Zbp1-positive cells are osteogenic progenitors in periodontal ligament

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