title: Simvastatin Promotes Dental Pulp Stem Cell-induced Coronal Pulp Regeneration in Pulpotomized Teeth.
abstract: BACKGROUND
  Pulpotomy is a specific treatment used to save root pulp, in which only the inflamed coronal pulp is removed and capping materials are placed. Our study aims to study the effect of simvastatin (1) on the proliferation and differentiation of dental pulp stem cells (DPSCs) and (2) on DPSC-induced pulp regeneration after pulpotomy.
  
  
  METHODS
  DPSCs were treated with different concentrations of simvastatin. Cell counting kit-8 activity was examined to test cell proliferation, and alkaline phosphatase assays and alizarin red S staining were conducted to examine differentiation. In addition, DPSCs pretreated with simvastatin were transplanted into the dorsum of CB-17 severe combined immunodeficiency mice. Areas of mineralized tissue were compared. Eighteen immature premolars from 2 beagle dogs were divided into 4 groups and treated by pulpotomy: the mineral trioxide aggregate, absorbable gelatin sponge, canine DPSCs (cDPSCs), and simvastatin groups. The teeth were extracted after 10 weeks, and the areas of regenerated pulp and dentin were calculated and compared.
  
  
  RESULTS
  Simvastatin at 1 μmol/L suppressed cDPSCs proliferation but significantly increased alkaline phosphatase activity and mineral nodule formation. In addition, cDPSCs pretreated with 1 μmol/L simvastatin formed significantly more mineralized tissue in CB-17 severe combined immunodeficiency mice. In the in vivo study, the ratios of the areas of pulp and dentin regeneration were 47.3% ± 2.5%, 76.8% ± 4.3%, and 85.8% ± 0.9%, respectively, in the absorbable gelatin sponge, cDPSCs, and simvastatin groups.
  
  
  CONCLUSIONS
  Simvastatin stimulates cDPSCs mineralization both in vivo and in vitro. It also promotes DPSC-induced pulp and dentin regeneration after pulpotomy.
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Weiqian
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Ling
authors.affiliation: Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China. Electronic address: gelh0919@126.com.
authors.forename: Lihong
authors.initials: L
authors.lastname: Ge
mesh_terms: D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D017610:Calcium Compounds / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000166:cytology*; D003809:Dentin, Secondary / Q000187:drug effects*; D004285:Dogs; D004338:Drug Combinations; D051379:Mice; D016513:Mice, SCID; D010087:Oxides / Q000494:pharmacology; D011672:Pulpotomy; D012038:Regeneration / Q000502:physiology*; D017640:Silicates / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology*; D033581:Stem Cell Transplantation
chemical_list: D017607:Aluminum Compounds; D001672:Biocompatible Materials; D017610:Calcium Compounds; D004338:Drug Combinations; D010087:Oxides; D017640:Silicates; C086631:mineral trioxide aggregate; D019821:Simvastatin
keywords: Beagle dog model; dentin regeneration; pulpotomy; simvastatin; stem cell differentiation