title: Expression of thymosin beta-4 in human periodontal ligament cells and mouse periodontal tissue and its role in osteoblastic/cementoblastic differentiation.
abstract: A recent report showed that thymosin beta-4 (Tβ4) is expressed during the development of tooth germ, but its effect on osteoblastic/cementoblastic differentiation is a controversial topic. Furthermore, the precise expression and function of Tβ4 in periodontal tissue remains unclear. Therefore, the purpose of this study was to investigate the immunolocalization of Tβ4 in the developing periodontium of mouse, the function of Tβ4 in osteoblastic/cementoblastic differentiation, and the underlying mechanism regulating periodontal regeneration in human periodontal ligament cells (hPDLCs), cementoblasts, and osteoblasts. Tβ4 expression was observed in differentiating hPDLCs, osteoblasts of the periodontium during development, as well as in mature tissue. Higher Tβ4 expression was observed in hPDLCs than in cementoblasts and osteoblasts in the developing periodontium. The expression of Tβ4 mRNA and protein gradually increased during PDL cell differentiation. The downregulation of Tβ4 expression by Tβ4 siRNA transfection inhibited osteoblastic differentiation by decreasing calcium nodule formation, alkaline phosphatase (ALP) activity, and mRNA expression of differentiation markers in hPDLCs, cementoblasts, and osteoblasts. In contrast, Tβ4 activation using a Tβ4 peptide, promoted these processes by activation of Akt, p38, ERK MAPKs, and the NF-κB pathway. The expression of nuclear NFATc1 was upregulated by Tβ4 peptide in hPDLCs. Inhibition of the calcineurin/NFATc1 pathway by cyclosporin A and FK506, attenuated Tβ4-induced osteoblastic differentiation and activation of Wnt-related genes, as well as nuclear β-catenin in hPDLCs. In conclusion, this study demonstrates, for the first time, that Tβ4 is expressed in developing periodontal tissue and that its expression is associated with osteoblastic/cementoblastic differentiation. These results suggests that Tβ4 is a potential therapeutic target for periodontal regeneration or bone disease.
authors.affiliation: Department of Dental Hygiene, School of Health Sciences, Dankook University, Cheonan, Republic of Korea.
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Deok-Won
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Department of Dental Hygiene, School of Health Sciences, Dankook University, Cheonan, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Parasitology and Genetic, Kosin University College of Medicine, Busan, Republic of Korea.
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Cheol-Hyeon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
authors.affiliation: Department of Oral and Maxillofacial Pathology and Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Republic of Korea. Electronic address: eckim@khu.ac.kr.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D003739:Dental Cementum / Q000166:cytology* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration; D013947:Thymosin / Q000096:biosynthesis* / Q000235:genetics; D000099201:Thymosin beta(4)
chemical_list: D000199:Actins; D034741:RNA, Small Interfering; D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: Differentiation; Expression; NFATc1; Periodontal ligament cells; Periodontium; Tβ4