title: The role of thymosin beta 4 on odontogenic differentiation in human dental pulp cells.
abstract: We recently reported that overexpression of thymosin beta-4 (Tβ4) in transgenic mice promotes abnormal hair growth and tooth development, but the role of Tβ4 in dental pulp regeneration was not completely understood. The aim of this study was to investigate the role of Tβ4 on odontoblastic differentiation and the underlying mechanism regulating pulp regeneration in human dental pulp cells (HDPCs). Our results demonstrate that mRNA and protein expression of Tβ4 is upregulated during odontogenic differentiation in HDPCs. Transfection with Tβ4 siRNA decreases OM-induced odontoblastic differentiation by decreasing alkaline phosphatase (ALP) activity, mRNA expression of differentiation markers, and calcium nodule formation. In contrast, Tβ4 activation with a Tβ4 peptide promotes these processes by enhancing the phosphorylation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs), bone morphogenetic protein (BMP) 2, BMP4, phosphorylation of Smad1/5/8 and Smad2/3, and expression of transcriptional factors such as Runx2 and Osterix, which were blocked by the BMP inhibitor noggin. The expression of integrin receptors α1, α2, α3, and β1 and downstream signaling molecules including phosphorylated focal adhesion kinase (p-FAK), p-paxillin, and integrin-linked kinase (ILK) were increased by Tβ4 peptide in HDPCs. ILK siRNA blocked Tβ4-induced odontoblastic differentiation and activation of the BMP and MAPK transcription factor pathways in HDPCs. In conclusion, this study demonstrates for the first time that Tβ4 plays a key role in odontoblastic differentiation of HDPCs and activation of Tβ4 could provide a novel mechanism for regenerative endodontics.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry and Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Lee
authors.forename: Duck-Su
authors.initials: DS
authors.lastname: Kim
authors.forename: Hwa-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009805:Odontogenesis / Q000187:drug effects / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013947:Thymosin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D000099201:Thymosin beta(4); D000099200:Scaffold Protein ILK
chemical_list: D019485:Bone Morphogenetic Proteins; D003470:Culture Media; D016023:Integrins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D013947:Thymosin; D014157:Transcription Factors; D000099201:Thymosin beta(4); D000099200:Scaffold Protein ILK