title: Effects of Activin A on the phenotypic properties of human periodontal ligament cells.
abstract: Periodontal ligament (PDL) tissue plays an important role in tooth preservation by structurally maintaining the connection between the tooth root and the bone. The mechanisms involved in the healing and regeneration of damaged PDL tissue, caused by bacterial infection, caries and trauma, have been explored. Accumulating evidence suggests that Activin A, a member of the transforming growth factor-β (TGF-β) superfamily and a dimer of inhibinβa, contributes to tissue healing through cell proliferation, migration, and differentiation of various target cells. In bone, Activin A has been shown to exert an inhibitory effect on osteoblast maturation and mineralization. However, there have been no reports examining the expression and function of Activin A in human PDL cells (HPDLCs). Thus, we aimed to investigate the biological effects of Activin A on HPDLCs. Activin A was observed to be localized in HPDLCs and rat PDL tissue. When PDL tissue was surgically damaged, Activin A and IL-1β expression increased and the two proteins were shown to be co-localized around the lesion. HPDLCs treated with IL-1β or TNF-α also up-regulated the expression of the gene encoding inhibinβa. Activin A promoted chemotaxis, migration and proliferation of HPDLCs, and caused an increase in fibroblastic differentiation of these cells while down-regulating their osteoblastic differentiation. These osteoblastic inhibitory effects of Activin A, however, were only noted during the early phase of HPDLC osteoblastic differentiation, with later exposures having no effect on differentiation. Collectively, our results suggest that Activin A could be used as a therapeutic agent for healing and regenerating PDL tissue in response to disease, trauma or surgical reconstruction.
authors.affiliation: Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Sugii
authors.affiliation: Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: hide@dent.kyushu-u.ac.jp.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Colgate Australian Clinical Dental Research Centre, School of Dentistry, University of Adelaide, SA 5005, Australia.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tomokiyo
authors.affiliation: Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Wada
authors.affiliation: Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Koori
authors.affiliation: Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Daigaku
authors.initials: D
authors.lastname: Hasegawa
authors.affiliation: Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Hamano
authors.affiliation: Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Yuda
authors.affiliation: Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Monnouchi
authors.affiliation: Department of Endodontology and Operative Dentistry, Faculty of Dental Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan; Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Akamine
mesh_terms: D029404:Activin Receptors / Q000378:metabolism; D028341:Activins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism* / Q000601:surgery; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C422405:activin A; D028341:Activins; D029404:Activin Receptors
keywords: Activin A; Fibroblastic differentiation; Migration; Osteoblastic differentiation; Periodontal ligament; Proliferation