Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo

J. D. Bradley, D. G. Cleverly, A. M. Burns, N. B. Helm, M. J. Schmid, D. B. Marx, D. M. Cullen, Richard A Reinhardt

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background and Objective: Simvastatin, a cholesterol-lowering drug, also stimulates oral bone growth when applied topically, without systemic side-effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein-2, nitric oxide synthase, and cyclooxygenase-2 are involved, based on prior in vitro evidence. Material and Methods: A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase-2 and bone morphogenetic protein-2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase-2 and nitric oxide synthase inhibitors (NS-398 and L-NAME, respectively) were administered intraperitoneally. Results: Simvastatin was found to stimulate local bone morphogenetic protein-2, nitric oxide and the regional bone formation rate (p < 0.05), whereas NS-398 inhibited bone morphogenetic protein-2 and reduced the bone formation rate (p < 0.05). Conclusion: These data suggest an association between simvastatin-induced bone morphogenetic protein-2 and bone formation in the mandibular microenvironment, and the negative effect of cyclooxygenase-2 inhibitors on bone growth.

Original languageEnglish (US)
Pages (from-to)267-273
Number of pages7
JournalJournal of Periodontal Research
Volume42
Issue number3
DOIs
StatePublished - Jun 1 2007

Fingerprint

Bone Morphogenetic Protein 2
Simvastatin
Cyclooxygenase 2 Inhibitors
Osteogenesis
Cyclooxygenase 2
Bone Development
Nitric Oxide Synthase
Nitric Oxide
Gels
Methylcellulose
NG-Nitroarginine Methyl Ester
Mandible
Immunoassay
Cholesterol
Enzymes
Pharmaceutical Preparations

Keywords

  • Bone formation rate
  • Bone morphogenetic protein-2
  • Cyclooxygenase-2
  • Simvastatin

ASJC Scopus subject areas

  • Periodontics

Cite this

Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo. / Bradley, J. D.; Cleverly, D. G.; Burns, A. M.; Helm, N. B.; Schmid, M. J.; Marx, D. B.; Cullen, D. M.; Reinhardt, Richard A.

In: Journal of Periodontal Research, Vol. 42, No. 3, 01.06.2007, p. 267-273.

Research output: Contribution to journalArticle

Bradley, J. D. ; Cleverly, D. G. ; Burns, A. M. ; Helm, N. B. ; Schmid, M. J. ; Marx, D. B. ; Cullen, D. M. ; Reinhardt, Richard A. / Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo. In: Journal of Periodontal Research. 2007 ; Vol. 42, No. 3. pp. 267-273.
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