Histone deacetylase inhibitors and periodontal bone loss

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.M. D. Cantley, P. M. Bartold, V. Marino, D. P. Fairlie, G. T. Le, A. J. Lucke, and D. R. Hayne