Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo.
Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mumol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs.
Okamoto
Yosuke
Y
Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Sonoyama
Wataru
W
Ono
Mitsuaki
M
Akiyama
Kentaro
K
Fujisawa
Takuo
T
Oshima
Masamitsu
M
Tsuchimoto
Yohei
Y
Matsuka
Yoshizo
Y
Yasuda
Tatsuji
T
Shi
Songtao
S
Kuboki
Takuo
T
D000328:Adult; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D003809:Dentin, Secondary / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D016193:G1 Phase / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D015675:Osteocalcin / Q000096:biosynthesis; D010750:Phosphoproteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins; D019821:Simvastatin / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects*; D015854:Up-Regulation; D055815:Young Adult; D000099311:Dentin Sialophosphoprotein
D055396:Bone Morphogenetic Protein 2; D016326:Extracellular Matrix Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015675:Osteocalcin; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D019821:Simvastatin; D000099311:Dentin Sialophosphoprotein