Activin A Promotes Osteoblastic Differentiation of Human Preosteoblasts through the ALK1-Smad1/5/9 Pathway |
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| Authors: | Hideki Sugii Mhd Safwan Albougha Orie Adachi Hiroka Tomita Atsushi Tomokiyo Sayuri Hamano Daigaku Hasegawa Shinichiro Yoshida Tomohiro Itoyama Hidefumi Maeda |
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| Affiliation: | 1. Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan; (M.S.A.); (O.A.); (H.T.); (S.H.); (H.M.);2. Department of Endodontology, Kyushu University Hospital, Fukuoka 812-8582, Japan; (A.T.); (D.H.); (S.Y.); (T.I.);3. OBT Center, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan |
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| Abstract: | 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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| Keywords: | activin A preosteoblast osteoblastic differentiation periodontal ligament ALK1 |
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