Tooth resorption in cats: contribution of vitamin D and inflammation

Abstract

Tooth resorption in cats Tooth resorption affecting several teeth is a painful disease with a prevalence of up to 75% in household cats and is often accompanied by periodontitis. Tooth resorption is caused by an increased number and activity of tooth-resorbing odontoclasts, cells that share functional characteristics with bone-resorbing osteoclasts. Both vitamin D and inflammatory cytokines stimulate the formation and activity of osteoclasts. Most mammals are able to synthesize vitamin D in their skin, but cats are not able to do so and thus depend on their dietary intake for their vitamin D requirements. Both a deficiency and an excess of dietary vitamin D have been hypothesized to be involved in tooth resorption. The overall focus of this thesis was to gain insight into the possible role of vitamin D and inflammation in tooth resorption in cats. Binding of 1,25-dihydroxycholecalciferol (1,25(OH)2D) to the nuclear vitamin D receptor (nVDR) of fibroblasts and odontoclasts near active resorptive lesions was found to induce the transcription of target genes of the vitamin D pathway, i.e. 1?-hydroxylase, 24-hydroxylase, receptor-activator of NF?B ligand (RANKL), and VDR itself. Inflammatory cells were often found in the resorption lacunae, and the expression of inflammatory cytokine was increased in surrounding tissues. The stimulatory effect of 1,25(OH)2D on osteoclast formation was demonstrated in vitro by the formation of tartrate-resistant acid phosphatase multinucleated cells from peripheral blood originating from cats with tooth resorption. Periodontal pathogenic bacteria may be part of the aetiopathogenesis of tooth resorption in cats through the lipopolysaccharide-induced increase in odontoclast activity. Two periodontal pathogens, Porphyromonas spp. and Tanerella forsythia, were found in dental plaque samples from cats. Two identical isolates of Tanerella forsythia of feline origin were found in a cat and its owner, which supported the idea that cats are a potential source of a periodontal zoonotic agent. Findings support the conclusion that odontoclast activity in cats with tooth resorption is stimulated by locally produced 1,25(OH)2D, facilitated through the nVDR expressing fibroblasts and odontoclasts and enhanced by inflammatory products. Local up-regulation of target genes of the vitamin D pathway further supports the observed increase in the activity of local vitamin D metabolites. We propose that not dietary vitamin D excess but inflammation-induced stimulation of the vitamin D pathway is involved in the pathogenesis of tooth resorption in cats.