title: TGF-Beta Negatively Regulates the BMP2-Dependent Early Commitment of Periodontal Ligament Cells into Hard Tissue Forming Cells.
abstract: Transforming growth factor beta (TGF-β) is a multi-functional growth factor expressed in many tissues and organs. Genetic animal models have revealed the critical functions of TGF-β in craniofacial development, including the teeth and periodontal tissue. However, the physiological function of TGF-β in the periodontal ligament (PDL) has not been fully elucidated. In this study, we examined the roles of TGF-β in the cytodifferentiation of PDL cells using a TGF-β receptor kinase inhibitor, SB431542. Mouse PDL cell clones (MPDL22) were cultured in calcification-inducing medium with or without SB431542 in the presence or absence of various growth factors, such as bone morphogenetic protein (BMP)-2, TGF-β and fibroblast growth factor (FGF)-2. SB431542 dramatically enhanced the BMP-2-dependent calcification of MPDL22 cells and accelerated the expression of ossification genes alkaline phosphatase (ALPase) and Runt-related transcription factor (Runx) 2 during early osteoblastic differentiation. SB431542 did not promote MPDL22 calcification without BMP-2 stimulation. The cell growth rate and collagen synthesis during the late stage of MPDL22 culture were retarded by SB431542. Quantitative reverse transcription polymerase chain reaction analysis revealed that the expressions of Smurf1 and Smad6, which are negative feedback components in the TGF-β/BMP signaling pathway, were downregulated in MPDL22 cells with SB431542 treatment. These results suggest that an endogenous signal from TGF-β negatively regulates the early commitment and cytodifferentiation of PDL cells into hard tissue-forming cells. A synthetic drug that regulates endogenous TGF-β signals may be efficacious for developing periodontal regenerative therapies.
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Kawahara
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Motozo
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Kuniko
authors.initials: K
authors.lastname: Ikegami
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yanagita
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: Department of Periodontology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita-Osaka 565-0871, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004149:Dioxoles / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008807:Mice, Inbred BALB C; D010513:Periodontal Ligament / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D055396:Bone Morphogenetic Protein 2; D004149:Dioxoles; D016212:Transforming Growth Factor beta