Histone deacetylase inhibitors and periodontal bone loss

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.