title: Nicotine stimulates osteoclast resorption in a porcine marrow cell model.
abstract: BACKGROUND
  Combustible tobacco use is generally linked with accelerated periodontal bone loss and diminished post-surgical wound healing; however, the pathogenesis of this process at the cellular level remains unclear. Nicotine is known to affect human gingival fibroblast orientation, attachment, and beta1 integrin expression, yet little is known about its effects on osteoclasts, the cells most responsible for bone resorption. The purpose of this study was to determine the effects of physiologically relevant nicotine levels on porcine osteoclast function as measured by resorption of calcium phosphate.
  
  
  METHODS
  Pure nicotine was diluted in medium to the following concentrations: 0.03 microM, 0.15 microM, 0.30 microM, 0.60 microM, and 1.50 microM. Porcine osteoclasts were seeded onto calcium phosphate multi-test slides and incubated at 37 degrees C with half media changes every 24 hours. Cells received 0, 0.15, 0.30, 0.60, and 1.50 microM nicotine, or 25 nM parathyroid hormone (PTH). Osteoclast resorption was quantified by measuring the resorbed surface area of the calcium phosphate substrate.
  
  
  RESULTS
  Osteoclast cultures resorbed bone slices and calcium phosphate substrate. All nicotine concentrations and PTH resulted in statistically significantly greater mean percent resorptions than the control group (P < 0.05). However, no statistical difference was found between the various nicotine doses or PTH. The number of osteoclasts increased in a linear relationship to the increasing nicotine concentrations; however, no correlation was found between osteoclast number and the amount of resorption.
  
  
  CONCLUSIONS
  Nicotine is non-toxic to osteoclasts at the clinically relevant levels tested. Nicotine appears to stimulate osteoclast differentiation and resorption of calcium phosphate, the major component of bone. Nicotine-modulated osteoclast stimulation may, in part, explain the increased rapidity of periodontal bone loss and refractory disease incidence in smokers.
authors.affiliation: Department of Clinical Investigation, Dwight D. Eisenhower Army Medical Center, Fort Gordon, GA 30905, USA.
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Henemyre
authors.forename: Donald K
authors.initials: DK
authors.lastname: Scales
authors.forename: Steven D
authors.initials: SD
authors.lastname: Hokett
authors.forename: Michael F
authors.initials: MF
authors.lastname: Cuenin
authors.forename: Mark E
authors.initials: ME
authors.lastname: Peacock
authors.forename: M Harry
authors.initials: MH
authors.lastname: Parker
authors.forename: Phyllis D
authors.initials: PD
authors.lastname: Brewer
authors.forename: Augustine H
authors.initials: AH
authors.lastname: Chuang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells; D001862:Bone Resorption / Q000139:chemically induced*; D002130:Calcium Phosphates / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D008855:Microscopy, Electron, Scanning; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D018709:Statistics, Nonparametric; D013552:Swine
chemical_list: D002130:Calcium Phosphates; D018722:Nicotinic Agonists; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D009538:Nicotine; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous