Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway

Activin A, a member of transforming growth factor-β superfamily, is involved in the regulation of cellular differentiation and promotes tissue healing. Previously, we reported that expression of activin A was upregulated around the damaged periodontal tissue including periodontal ligament (PDL) tiss...

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Main Authors: Hideki Sugii, Mhd Safwan Albougha, Orie Adachi, Hiroka Tomita, Atsushi Tomokiyo, Sayuri Hamano, Daigaku Hasegawa, Shinichiro Yoshida, Tomohiro Itoyama, Hidefumi Maeda
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/24/13491
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author Hideki Sugii
Mhd Safwan Albougha
Orie Adachi
Hiroka Tomita
Atsushi Tomokiyo
Sayuri Hamano
Daigaku Hasegawa
Shinichiro Yoshida
Tomohiro Itoyama
Hidefumi Maeda
author_facet Hideki Sugii
Mhd Safwan Albougha
Orie Adachi
Hiroka Tomita
Atsushi Tomokiyo
Sayuri Hamano
Daigaku Hasegawa
Shinichiro Yoshida
Tomohiro Itoyama
Hidefumi Maeda
author_sort Hideki Sugii
collection DOAJ
description Activin A, a member of transforming growth factor-β superfamily, is involved in the regulation of cellular differentiation and promotes tissue healing. Previously, we reported that expression of activin A was upregulated around the damaged periodontal tissue including periodontal ligament (PDL) tissue and alveolar bone, and activin A promoted PDL-related gene expression of human PDL cells (HPDLCs). However, little is known about the biological function of activin A in alveolar bone. Thus, this study analyzed activin A-induced biological functions in preosteoblasts (Saos2 cells). Activin A promoted osteoblastic differentiation of Saos2 cells. Activin receptor-like kinase (ALK) 1, an activin type I receptor, was more strongly expressed in Saos2 cells than in HPDLCs, and knockdown of ALK1 inhibited activin A-induced osteoblastic differentiation of Saos2 cells. Expression of ALK1 was upregulated in alveolar bone around damaged periodontal tissue when compared with a nondamaged site. Furthermore, activin A promoted phosphorylation of Smad1/5/9 during osteoblastic differentiation of Saos2 cells and knockdown of ALK1 inhibited activin A-induced phosphorylation of Smad1/5/9 in Saos2 cells. Collectively, these findings suggest that activin A promotes osteoblastic differentiation of preosteoblasts through the ALK1-Smad1/5/9 pathway and could be used as a therapeutic product for the healing of alveolar bone as well as PDL tissue.
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spelling doaj.art-abb03ec4a3e246f989044e57278b51662023-11-23T08:47:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241349110.3390/ijms222413491Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 PathwayHideki Sugii0Mhd Safwan Albougha1Orie Adachi2Hiroka Tomita3Atsushi Tomokiyo4Sayuri Hamano5Daigaku Hasegawa6Shinichiro Yoshida7Tomohiro Itoyama8Hidefumi Maeda9 Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan Department of Endodontology, Kyushu University Hospital, Fukuoka 812-8582, Japan Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan Department of Endodontology, Kyushu University Hospital, Fukuoka 812-8582, Japan Department of Endodontology, Kyushu University Hospital, Fukuoka 812-8582, Japan Department of Endodontology, Kyushu University Hospital, Fukuoka 812-8582, Japan Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, JapanActivin A, a member of transforming growth factor-β superfamily, is involved in the regulation of cellular differentiation and promotes tissue healing. Previously, we reported that expression of activin A was upregulated around the damaged periodontal tissue including periodontal ligament (PDL) tissue and alveolar bone, and activin A promoted PDL-related gene expression of human PDL cells (HPDLCs). However, little is known about the biological function of activin A in alveolar bone. Thus, this study analyzed activin A-induced biological functions in preosteoblasts (Saos2 cells). Activin A promoted osteoblastic differentiation of Saos2 cells. Activin receptor-like kinase (ALK) 1, an activin type I receptor, was more strongly expressed in Saos2 cells than in HPDLCs, and knockdown of ALK1 inhibited activin A-induced osteoblastic differentiation of Saos2 cells. Expression of ALK1 was upregulated in alveolar bone around damaged periodontal tissue when compared with a nondamaged site. Furthermore, activin A promoted phosphorylation of Smad1/5/9 during osteoblastic differentiation of Saos2 cells and knockdown of ALK1 inhibited activin A-induced phosphorylation of Smad1/5/9 in Saos2 cells. Collectively, these findings suggest that activin A promotes osteoblastic differentiation of preosteoblasts through the ALK1-Smad1/5/9 pathway and could be used as a therapeutic product for the healing of alveolar bone as well as PDL tissue.https://www.mdpi.com/1422-0067/22/24/13491activin Apreosteoblastosteoblastic differentiationperiodontal ligamentALK1
spellingShingle Hideki Sugii
Mhd Safwan Albougha
Orie Adachi
Hiroka Tomita
Atsushi Tomokiyo
Sayuri Hamano
Daigaku Hasegawa
Shinichiro Yoshida
Tomohiro Itoyama
Hidefumi Maeda
Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway
International Journal of Molecular Sciences
activin A
preosteoblast
osteoblastic differentiation
periodontal ligament
ALK1
title Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway
title_full Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway
title_fullStr Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway
title_full_unstemmed Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway
title_short Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway
title_sort activin a promotes osteoblastic differentiation of human preosteoblasts through the alk1 smad1 5 9 pathway
topic activin A
preosteoblast
osteoblastic differentiation
periodontal ligament
ALK1
url https://www.mdpi.com/1422-0067/22/24/13491
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