PMID- 21236710 OWN - NLM STAT- MEDLINE DCOM- 20110628 LR - 20211203 IS - 1528-395X (Electronic) IS - 1079-2104 (Linking) VI - 111 IP - 3 DP - 2011 Mar TI - Transforming growth factor beta1 down-regulates Runx-2 and alkaline phosphatase activity of human dental pulp cells via ALK5/Smad2/3 signaling. PG - 394-400 LID - 10.1016/j.tripleo.2010.09.079 [doi] AB - OBJECTIVE: Transforming growth factor beta1 (TGF-beta1) plays a role in repair and dentinogenesis in dental pulp. The purpose of this study was to study how TGF-beta1 affects 2 differentiation markers, Runt-related transcription factor 2 (Runx-2) and ALP, in dental pulp cells. STUDY DESIGN: Primary-cultured human dental pulp cells were treated with TGF-beta1 with or without pretreatment and coincubation with 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene (U0126, a mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor), Noggin (a bone morphogenetic protein inhibitor), or 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H-imidazol-2-yl)-benzamide hydrate (SB431542, an activin receptor-like kinase (ALK) 5/Smad2/3 inhibitor). The differentiation status of pulp cells was evaluated by ALP staining and quantitative ALP activity assay. Changes in ALP and Runx-2 mRNA expression were determined by reverse-transcription polymerase chain reaction. RESULTS: Cells under the treatment of TGF-beta1 (5 and 10 ng/mL) showed a decrease in ALP activity and gene expression of ALP and Runx-2. Pretreatment by U0126 and Noggin was not effective to prevent the TGF-beta1-induced decline of ALP activity. Interestingly, SB431542 prevented the TGF-beta1-induced decline of ALP activity and ALP and Runx-2 gene expression. CONCLUSION: TGF-beta1 down-regulates Runx-2 and ALP in human dental pulp cells via ALK5/Smad2/3 signaling. These events may play important roles at specific stages of pulpal repair and dentinogenesis. CI - Copyright (c) 2011 Mosby, Inc. All rights reserved. FAU - Lin, Po-Shuen AU - Lin PS AD - Department of Dentistry/School of Dentistry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. FAU - Chang, Mei-Chi AU - Chang MC FAU - Chan, Chiu-Po AU - Chan CP FAU - Lee, Sheng-Yang AU - Lee SY FAU - Lee, Jang-Jaer AU - Lee JJ FAU - Tsai, Yi-Ling AU - Tsai YL FAU - Tseng, Hui-Chun AU - Tseng HC FAU - Tai, Tseng-Fang AU - Tai TF FAU - Lin, Hsueh-Jen AU - Lin HJ FAU - Jeng, Jiiang-Huei AU - Jeng JH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110113 PL - United States TA - Oral Surg Oral Med Oral Pathol Oral Radiol Endod JT - Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics JID - 9508562 RN - 0 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide) RN - 0 (Benzamides) RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Butadienes) RN - 0 (Carrier Proteins) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Dioxoles) RN - 0 (Enzyme Inhibitors) RN - 0 (Nitriles) RN - 0 (RUNX2 protein, human) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (SMAD2 protein, human) RN - 0 (SMAD3 protein, human) RN - 0 (Smad2 Protein) RN - 0 (Smad3 Protein) RN - 0 (Transforming Growth Factor beta1) RN - 0 (U 0126) RN - 148294-77-3 (noggin protein) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I) RN - EC 2.7.11.30 (TGFBR1 protein, human) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Alkaline Phosphatase/antagonists & inhibitors/*metabolism MH - Benzamides/pharmacology MH - Bone Morphogenetic Proteins/antagonists & inhibitors MH - Butadienes/pharmacology MH - Carrier Proteins/pharmacology MH - Cells, Cultured MH - Core Binding Factor Alpha 1 Subunit/antagonists & inhibitors/*metabolism MH - Dental Pulp/cytology/enzymology/*metabolism MH - Dioxoles/pharmacology MH - Down-Regulation/*physiology MH - Enzyme Inhibitors/pharmacology MH - Humans MH - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors MH - Nitriles/pharmacology MH - Protein Serine-Threonine Kinases/antagonists & inhibitors/*metabolism MH - Receptor, Transforming Growth Factor-beta Type I MH - Receptors, Transforming Growth Factor beta/antagonists & inhibitors/*metabolism MH - Signal Transduction/drug effects/*physiology MH - Smad2 Protein/antagonists & inhibitors/*metabolism MH - Smad3 Protein/antagonists & inhibitors/*metabolism MH - Transforming Growth Factor beta1/*metabolism/pharmacology EDAT- 2011/01/18 06:00 MHDA- 2011/06/29 06:00 CRDT- 2011/01/18 06:00 PHST- 2010/08/03 00:00 [received] PHST- 2010/08/24 00:00 [revised] PHST- 2010/09/29 00:00 [accepted] PHST- 2011/01/18 06:00 [entrez] PHST- 2011/01/18 06:00 [pubmed] PHST- 2011/06/29 06:00 [medline] AID - S1079-2104(10)00798-5 [pii] AID - 10.1016/j.tripleo.2010.09.079 [doi] PST - ppublish SO - Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011 Mar;111(3):394-400. doi: 10.1016/j.tripleo.2010.09.079. Epub 2011 Jan 13.