title: Nicotine stimulation increases proliferation and matrix metalloproteinases-2 and -28 expression in human dental pulp cells.
abstract: OBJECTIVE
  Dental pulp is the specialized tissue responsible for maintaining tooth viability. When tooth mineralized matrix is damaged, pulp is exposed to a plethora of environmental stimuli. In particular, in smokers, pulp become exposed to very high concentrations of nicotine. The aim of this study was to investigate the effect of direct nicotine stimulation on human dental pulp cell proliferation. Moreover, as it is known that nicotine could upregulate the expression of matrix metalloproteinases (MMPs), enzymes involved in pulpal inflammation, the effects of nicotine stimulation on MMP-2 and MMP-28 gene expression have also been investigated.
  
  
  METHODS
  Human dental pulp cells were extracted from impacted third molars obtained from healthy patients undergoing routine orthodontic treatments. Such cells were treated with growing concentrations of nicotine in the presence or absence of a nicotine antagonist (hexamethonium chloride) or of a MEK signaling inhibitor (PD98059). Cell proliferation was evaluated by cell counting, while nicotine effects on MMP expression were evaluated by PCR.
  
  
  RESULTS
  The data obtained indicate that nicotine is able to increase human dental pulp cell proliferation by acting through nicotinic cholinergic receptors and downstream MAPK signaling pathway. Moreover, it is also able to increase both MMP-2 and MMP-28 gene expression.
  
  
  CONCLUSIONS
  In summary these results highlight that direct exposure of human dental pulp cells to nicotine results in an inflammatory response, that could have a role in pulpal inflammation onset, a pathological condition that, when ignored, could eventually spread to the surrounding alveolar bone and progress to pulp necrosis.
authors.affiliation: Innovative Research Laboratory for Wound Healing, Health Sciences Department, Università del Piemonte Orientale "A. Avogadro", via Solaroli, 17, 28100 Novara, Italy. Electronic address: manuela.rizzi@med.unipmn.it.
authors.forename: Rizzi
authors.initials: R
authors.lastname: Manuela
authors.affiliation: Dental Clinic, Health Sciences Department, Università del Piemonte Orientale "A. Avogadro", via Solaroli, 17, 28100 Novara, Italy. Electronic address: mario.migliario@med.unipmn.it.
authors.forename: Migliario
authors.initials: M
authors.lastname: Mario
authors.affiliation: Dental Clinic, Health Sciences Department, Università del Piemonte Orientale "A. Avogadro", via Solaroli, 17, 28100 Novara, Italy. Electronic address: vincenzo.rocchetti@alice.it.
authors.forename: Rocchetti
authors.initials: R
authors.lastname: Vincenzo
authors.affiliation: Innovative Research Laboratory for Wound Healing, Health Sciences Department, Università del Piemonte Orientale "A. Avogadro", via Solaroli, 17, 28100 Novara, Italy. Electronic address: filippo.reno@med.unipmn.it.
authors.forename: Renò
authors.initials: R
authors.lastname: Filippo
mesh_terms: D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000201:enzymology*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D018738:Hexamethonium / Q000494:pharmacology; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D053505:Matrix Metalloproteinases, Secreted / Q000096:biosynthesis*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D005419:Flavonoids; D005730:Ganglionic Blockers; D005731:Ganglionic Stimulants; D018738:Hexamethonium; D009538:Nicotine; D020930:MAP Kinase Kinase Kinases; C424663:MMP28 protein, human; D053505:Matrix Metalloproteinases, Secreted; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: Dental pulp; Hexamethonium chloride; MAPK; MMPs; Nicotine