title: Effects of a triple antibiotic solution on pulpal dynamics after intentionally delayed tooth replantation in mice.
abstract: BACKGROUND
  This study analyzed the detailed biological events underlying pulpal dynamics evoked by 3Mix (the mixture of ciprofloxacin, metronidazole, and minocycline) solution after intentionally delayed tooth replantation because 3Mix improves pulpal healing after tooth injuries.
  
  
  METHODS
  The maxillary first molars of 3-week-old mice were extracted and immersed in 3Mix solution for 30 minutes in comparison with phosphate buffered saline (PBS) alone. Cell proliferation, apoptosis, and differentiation were assessed in extracted/replanted teeth during days 0-14 using immunohistochemistry, apoptosis assay, and reverse-transcriptase polymerase chain reaction.
  
  
  RESULTS
  3Mix solution accelerated odontoblast differentiation in the coronal pulp on day 7 and tertiary dentin formation on day 14, whereas the regenerative process was delayed in the PBS group. Cell proliferation and apoptosis occurred in the pulp of the 3Mix group during days 5-7 and subsequently decreased from days 7-14. On day 5, dentin sialophosphoprotein and nestin were first recovered in the 3Mix group, whereas expression levels for alkaline phosphatase, osteopontin, and osteocalcin increased in the PBS group. The expression levels for octamer-binding factor 3/4A and 3/4B reached the maximum level on day 1 and were sharply decreased on day 3 in both groups. High expression levels of Cd11c were first observed in the 3Mix group on day 1 and later at days 5 and 7.
  
  
  CONCLUSIONS
  The results suggest that the application of 3Mix may suppress osteoblast differentiation by the migration of dendritic cells to the injury site and via the activation of stem/progenitor cells, resulting in the acceleration of odontoblastlike cell differentiation.
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Angela
authors.initials: A
authors.lastname: Quispe-Salcedo
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan. Electronic address: histoman@dent.niigata-u.ac.jp.
authors.forename: Hayato
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D000469:Alkaline Phosphatase / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002021:Buffers; D018845:CD11 Antigens / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002939:Ciprofloxacin / Q000627:therapeutic use; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D003809:Dentin, Secondary / Q000187:drug effects; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins / Q000187:drug effects; D008795:Metronidazole / Q000627:therapeutic use; D051379:Mice; D008911:Minocycline / Q000627:therapeutic use; D064231:Nestin / Q000187:drug effects; D050814:Octamer Transcription Factor-3 / Q000187:drug effects; D009804:Odontoblasts / Q000187:drug effects; D019188:Organ Preservation Solutions / Q000627:therapeutic use*; D015675:Osteocalcin / Q000187:drug effects; D053495:Osteopontin / Q000187:drug effects; D010710:Phosphates; D010750:Phosphoproteins / Q000187:drug effects; D012795:Sialoglycoproteins / Q000187:drug effects; D012965:Sodium Chloride; D013997:Time Factors; D014090:Tooth Replantation / Q000379:methods*; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D000900:Anti-Bacterial Agents; D002021:Buffers; D018845:CD11 Antigens; D002939:Ciprofloxacin; D004338:Drug Combinations; D016326:Extracellular Matrix Proteins; D008795:Metronidazole; D008911:Minocycline; D064231:Nestin; D050814:Octamer Transcription Factor-3; D019188:Organ Preservation Solutions; D015675:Osteocalcin; D053495:Osteopontin; D010710:Phosphates; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D012965:Sodium Chloride; D000099311:Dentin Sialophosphoprotein; C577485:Nes protein, mouse; C506896:Spp1 protein, mouse
keywords: Antimicrobial; Crlj:CD1 (ICR) mice; apoptosis; cell differentiation; cell proliferation; dental pulp; odontoblasts; regeneration; tooth replantation