MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells

Periodontal ligament (PDL) stem cells (PDLSCs) have been reported as a useful cell source for periodontal tissue regeneration. However, one of the issues is the difficulty of obtaining a sufficient number of PDLSCs for clinical application because very few PDLSCs can be isolated from PDL tissue of d...

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Main Authors: Daigaku Hasegawa, Kana Hasegawa, Hiroshi Kaneko, Shinichiro Yoshida, Hiromi Mitarai, Mai Arima, Atsushi Tomokiyo, Sayuri Hamano, Hideki Sugii, Naohisa Wada, Tamotsu Kiyoshima, Hidefumi Maeda
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2020/9672673
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author Daigaku Hasegawa
Kana Hasegawa
Hiroshi Kaneko
Shinichiro Yoshida
Hiromi Mitarai
Mai Arima
Atsushi Tomokiyo
Sayuri Hamano
Hideki Sugii
Naohisa Wada
Tamotsu Kiyoshima
Hidefumi Maeda
author_facet Daigaku Hasegawa
Kana Hasegawa
Hiroshi Kaneko
Shinichiro Yoshida
Hiromi Mitarai
Mai Arima
Atsushi Tomokiyo
Sayuri Hamano
Hideki Sugii
Naohisa Wada
Tamotsu Kiyoshima
Hidefumi Maeda
author_sort Daigaku Hasegawa
collection DOAJ
description Periodontal ligament (PDL) stem cells (PDLSCs) have been reported as a useful cell source for periodontal tissue regeneration. However, one of the issues is the difficulty of obtaining a sufficient number of PDLSCs for clinical application because very few PDLSCs can be isolated from PDL tissue of donors. Therefore, we aimed to identify a specific factor that converts human PDL cells into stem-like cells. In this study, microarray analysis comparing the gene profiles of human PDLSC lines (2-14 and 2-23) with those of a cell line with a low differentiation potential (2-52) identified the imprinted gene mesoderm-specific transcript (MEST). MEST was expressed in the cytoplasm of 2-23 cells. Knockdown of MEST by siRNA in 2-23 cells inhibited the expression of stem cell markers, such as CD105, CD146, p75NTR, N-cadherin, and NANOG; the proliferative potential; and multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes. On the other hand, overexpression of MEST in 2-52 cells enhanced the expression of stem cell markers and PDL-related markers and the multidifferentiation capacity. In addition, MEST-overexpressing 2-52 cells exhibited a change in morphology from a spindle shape to a stem cell-like round shape that was similar to 2-14 and 2-23 cell morphologies. These results suggest that MEST plays a critical role in the maintenance of stemness in PDLSCs and converts PDL cells into PDLSC-like cells. Therefore, this study indicates that MEST may be a therapeutic factor for periodontal tissue regeneration by inducing PDLSCs.
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spelling doaj-art-39551639219d4e94b8c0aa9ac7afebc52025-02-03T01:03:59ZengWileyStem Cells International1687-966X1687-96782020-01-01202010.1155/2020/96726739672673MEST Regulates the Stemness of Human Periodontal Ligament Stem CellsDaigaku Hasegawa0Kana Hasegawa1Hiroshi Kaneko2Shinichiro Yoshida3Hiromi Mitarai4Mai Arima5Atsushi Tomokiyo6Sayuri Hamano7Hideki Sugii8Naohisa Wada9Tamotsu Kiyoshima10Hidefumi Maeda11Department of Endodontology, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Oral Pathology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDivision of General Dentistry, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDivision of General Dentistry, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Oral Pathology, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanDepartment of Endodontology, Kyushu University Hospital, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, JapanPeriodontal ligament (PDL) stem cells (PDLSCs) have been reported as a useful cell source for periodontal tissue regeneration. However, one of the issues is the difficulty of obtaining a sufficient number of PDLSCs for clinical application because very few PDLSCs can be isolated from PDL tissue of donors. Therefore, we aimed to identify a specific factor that converts human PDL cells into stem-like cells. In this study, microarray analysis comparing the gene profiles of human PDLSC lines (2-14 and 2-23) with those of a cell line with a low differentiation potential (2-52) identified the imprinted gene mesoderm-specific transcript (MEST). MEST was expressed in the cytoplasm of 2-23 cells. Knockdown of MEST by siRNA in 2-23 cells inhibited the expression of stem cell markers, such as CD105, CD146, p75NTR, N-cadherin, and NANOG; the proliferative potential; and multidifferentiation capacity for osteoblasts, adipocytes, and chondrocytes. On the other hand, overexpression of MEST in 2-52 cells enhanced the expression of stem cell markers and PDL-related markers and the multidifferentiation capacity. In addition, MEST-overexpressing 2-52 cells exhibited a change in morphology from a spindle shape to a stem cell-like round shape that was similar to 2-14 and 2-23 cell morphologies. These results suggest that MEST plays a critical role in the maintenance of stemness in PDLSCs and converts PDL cells into PDLSC-like cells. Therefore, this study indicates that MEST may be a therapeutic factor for periodontal tissue regeneration by inducing PDLSCs.http://dx.doi.org/10.1155/2020/9672673
spellingShingle Daigaku Hasegawa
Kana Hasegawa
Hiroshi Kaneko
Shinichiro Yoshida
Hiromi Mitarai
Mai Arima
Atsushi Tomokiyo
Sayuri Hamano
Hideki Sugii
Naohisa Wada
Tamotsu Kiyoshima
Hidefumi Maeda
MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
Stem Cells International
title MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
title_full MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
title_fullStr MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
title_full_unstemmed MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
title_short MEST Regulates the Stemness of Human Periodontal Ligament Stem Cells
title_sort mest regulates the stemness of human periodontal ligament stem cells
url http://dx.doi.org/10.1155/2020/9672673
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