Effect of simvastatin prodrug on experimental periodontitis

Aaron D. Bradley, Yijia Zhang, Zhenshan Jia, Gang Zhao, Xiaobei Wang, Laura Pranke, Marian J. Schmid, Dong Wang, Richard A Reinhardt

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation. Methods: Forty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis between maxillary first and second molars (M1-M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM/SIM-mPEG); 3) 1.0 mg SIM/SIM-mPEG; 4) 1.5 mg SIM/SIM-mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1-M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one-way analysis of variance. Results: Ligature alone caused a mean bone loss of 1.01 ± 0.06 mm from the cemento-enamel junction, whereas all doses of SIM/SIM-mPEG reduced bone loss, especially 1.5 mg SIM/SIM-mPEG (0.68 ± 0.05 mm, P <0.001), which was not statistically different from contralateral control (0.47 ± 0.06 mm). A dose of 1.5 mg SIM/SIM-mPEG also reduced percentage of neutrophils compared with carrier alone (2.0% ± 1.0% versus 5.7% ± 1.1%; P <0.05), and increased amount of uninflamed connective tissue in the M1-M2 interproximal area (65.2% ± 3.3% versus 46.3% ± 3.3%; P <0.001). The mPEG carrier alone did not have bonesparing or anti-inflammatory properties. Conclusion: Multiple local 1.5-mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.

Original languageEnglish (US)
Pages (from-to)577-582
Number of pages6
JournalJournal of periodontology
Volume87
Issue number5
DOIs
StatePublished - May 2016

Fingerprint

Simvastatin
Periodontitis
Prodrugs
Ligation
Osteitis
Bone and Bones
Hydroxymethylglutaryl-CoA Reductase Inhibitors
X-Ray Microtomography
Dental Enamel
Connective Tissue

Keywords

  • Histology
  • Hydroxymethylglutaryl-coa reductase inhibitors
  • Micelles
  • Periodontitis
  • X-ray microtomography

ASJC Scopus subject areas

  • Periodontics

Cite this

Effect of simvastatin prodrug on experimental periodontitis. / Bradley, Aaron D.; Zhang, Yijia; Jia, Zhenshan; Zhao, Gang; Wang, Xiaobei; Pranke, Laura; Schmid, Marian J.; Wang, Dong; Reinhardt, Richard A.

In: Journal of periodontology, Vol. 87, No. 5, 05.2016, p. 577-582.

Research output: Contribution to journalArticle

Bradley, AD, Zhang, Y, Jia, Z, Zhao, G, Wang, X, Pranke, L, Schmid, MJ, Wang, D & Reinhardt, RA 2016, 'Effect of simvastatin prodrug on experimental periodontitis', Journal of periodontology, vol. 87, no. 5, pp. 577-582. https://doi.org/10.1902/jop.2016.150599
Bradley, Aaron D. ; Zhang, Yijia ; Jia, Zhenshan ; Zhao, Gang ; Wang, Xiaobei ; Pranke, Laura ; Schmid, Marian J. ; Wang, Dong ; Reinhardt, Richard A. / Effect of simvastatin prodrug on experimental periodontitis. In: Journal of periodontology. 2016 ; Vol. 87, No. 5. pp. 577-582.
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abstract = "Background: Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation. Methods: Forty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis between maxillary first and second molars (M1-M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM/SIM-mPEG); 3) 1.0 mg SIM/SIM-mPEG; 4) 1.5 mg SIM/SIM-mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1-M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one-way analysis of variance. Results: Ligature alone caused a mean bone loss of 1.01 ± 0.06 mm from the cemento-enamel junction, whereas all doses of SIM/SIM-mPEG reduced bone loss, especially 1.5 mg SIM/SIM-mPEG (0.68 ± 0.05 mm, P <0.001), which was not statistically different from contralateral control (0.47 ± 0.06 mm). A dose of 1.5 mg SIM/SIM-mPEG also reduced percentage of neutrophils compared with carrier alone (2.0{\%} ± 1.0{\%} versus 5.7{\%} ± 1.1{\%}; P <0.05), and increased amount of uninflamed connective tissue in the M1-M2 interproximal area (65.2{\%} ± 3.3{\%} versus 46.3{\%} ± 3.3{\%}; P <0.001). The mPEG carrier alone did not have bonesparing or anti-inflammatory properties. Conclusion: Multiple local 1.5-mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.",
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AU - Zhao, Gang

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AU - Pranke, Laura

AU - Schmid, Marian J.

AU - Wang, Dong

AU - Reinhardt, Richard A

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N2 - Background: Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation. Methods: Forty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis between maxillary first and second molars (M1-M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM/SIM-mPEG); 3) 1.0 mg SIM/SIM-mPEG; 4) 1.5 mg SIM/SIM-mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1-M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one-way analysis of variance. Results: Ligature alone caused a mean bone loss of 1.01 ± 0.06 mm from the cemento-enamel junction, whereas all doses of SIM/SIM-mPEG reduced bone loss, especially 1.5 mg SIM/SIM-mPEG (0.68 ± 0.05 mm, P <0.001), which was not statistically different from contralateral control (0.47 ± 0.06 mm). A dose of 1.5 mg SIM/SIM-mPEG also reduced percentage of neutrophils compared with carrier alone (2.0% ± 1.0% versus 5.7% ± 1.1%; P <0.05), and increased amount of uninflamed connective tissue in the M1-M2 interproximal area (65.2% ± 3.3% versus 46.3% ± 3.3%; P <0.001). The mPEG carrier alone did not have bonesparing or anti-inflammatory properties. Conclusion: Multiple local 1.5-mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.

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