Histone deacetylase inhibitors and periodontal bone loss

J Periodontal Res. 2011 Dec;46(6):697-703. doi: 10.1111/j.1600-0765.2011.01392.x. Epub 2011 Jul 11.

Abstract

Background and objective: Bone loss caused by enhanced osteoclast activity is a significant feature of periodontitis. Histone deacetylase inhibitors (HDACi) can suppress osteoclast-mediated bone loss in vitro and in vivo. This study investigated whether HDACi can suppress bone loss in experimental periodontitis.

Material and methods: Experimental periodontitis was induced in mice by oral inoculation with Porphyromonas gingivalis bacteria. Mice were treated orally with olive oil alone, with olive oil and a novel compound - 1179.4b - which targets both Class I and Class II histone deacetylases (HDACs) or with olive oil and MS-275, which targets Class I HDACs. Micro-computed tomography scans of live mice, stereo imaging and histological analyses were used to detect changes in bone.

Results: In the absence of treatment there was a 13.2% increase in bone volume in controls compared with a 7.4% decrease in P. gingivalis-inoculated mice. 1179.4b significantly reduced bone loss, with a 3.4% increase in bone volume (p < 0.01). MS-275 did not have a significant effect on P. gingivalis-induced bone loss. Histological analysis revealed that 1179.4b reduced bone loss despite having no effect on inflammation.

Conclusion: HDACi were found to effectively suppress bone loss in the mouse model of periodontitis. 1179.4b - the inhibitor of Class I and Class II HDACs - was more effective at suppressing bone loss than MS-275, which targets Class I HDACs only. These compounds may therefore have the potential to be used for the management of periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Bone Loss / diagnostic imaging
  • Alveolar Bone Loss / enzymology*
  • Alveolar Bone Loss / prevention & control*
  • Aminoquinolines / therapeutic use
  • Animals
  • Benzamides / therapeutic use
  • Bone Density
  • Female
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Hydroxamic Acids / therapeutic use
  • Imaging, Three-Dimensional
  • Mice
  • Mice, Inbred BALB C
  • Olive Oil
  • Osteoclasts / pathology
  • Periodontitis / enzymology
  • Plant Oils / therapeutic use
  • Porphyromonas gingivalis
  • Pyridines / therapeutic use
  • X-Ray Microtomography

Substances

  • Aminoquinolines
  • Benzamides
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • N8-hydroxy-2-(1H-indole-2-carboxamido)-N1-(quinolin-8-yl)octanediamide
  • Olive Oil
  • Plant Oils
  • Pyridines
  • entinostat