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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2021-12-01
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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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