title: Differential effects of TGF-β1 and FGF-2 on SDF-1α expression in human             periodontal ligament cells derived from deciduous teeth in vitro.
abstract: Stromal cell-derived factor (SDF)-1α has been reported to play a crucial role in stem cell homing and recruitment to injured sites. However, no information is available about its role in periodontal tissues. The aim of this in vitro study was to investigate the effects of basic fibroblast growth factor (FGF-2) and transforming growth factor (TGF)-β1 on SDF-1α expression in immortalized periodontal ligament (PDL) cells derived from deciduous teeth (SH9 cells). Real-time PCR and western blot analyses showed that SDF-1α mRNA expression in SH9 cells was markedly inhibited by FGF-2 treatment for 48 h. SU5402, which directly interacts with the catalytic domain of the FGF receptor 1 (FGFR1) and suppresses its phosphorylation, inhibited the FGF-2-related decrease in SDF-1α expression. These results suggest that FGF-2 signaling via the FGFR1 pathway inhibits SDF-1α expression. Conversely, SDF-1α expression in SH9 cells was increased by TGF-β1 treatment for 12 h. Western blot analysis showed that this treatment induced Smad2/3 phosphorylation. A time-course experiment showed that SDF-1α expression levels reached a maximum 12 h after the TGF-β1 treatment and returned to basal levels by 48 h. Real-time PCR analysis showed that Smad7 mRNA expression peaked by 6 h after TGF-β1 treatment. Since Smad7 siRNA downregulated Smad7 expression by approximately 2.5-fold compared with the negative control siRNA, the induction of SDF-1α expression was prolonged. Furthermore, treatment of SH9 cells with TGF-β1 for 12 h induced transwell migration of UE7T-13 cells, which are mesenchymal stem cells derived from human bone marrow. Therefore, SDF-1α may play an important role in stem and progenitor cell recruitment and homing to injured sites in the periodontal ligament, and regulation of SDF-1α expression may be a useful tool in cell-based therapy for periodontal tissue regeneration.
authors.affiliation: Department of Pediatric Dentistry, Tokushima University Hospital, Tokushima 770-8504, Japan. hasegawa@dent.tokushima-u.ac.jp
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Chosa
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Asakawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fujihara
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kitamura
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Ishisaki
authors.forename: Masato
authors.initials: M
authors.lastname: Mitome
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010513:Periodontal Ligament / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000096:biosynthesis / Q000235:genetics; D014094:Tooth, Deciduous; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D054377:Chemokine CXCL12; D011758:Pyrroles; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017468:Receptors, Fibroblast Growth Factor; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; C497806:SMAD7 protein, human; C105686:SU 5402; D051899:Smad2 Protein; D051900:Smad3 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2