Reduced orthodontic tooth movement in Ank knockout mice.

Abstract

Hypercementosis has been previously reported in mice lacking progressive ankylosis protein (Ank KO mice, or Ank, KO - knockout, WT - wildtype) due to decreased levels of the mineralization inhibitor inorganic pyrophosphate. However, the impact of hypercementosis on alveolar bone remodeling and periodontal ligament (PDL) maintenance from orthodontic forces during orthodontic tooth movement (OTM) remains unclear. To investigate the roles of ANK protein on tooth movement, PDL maintenance, alveolar bone remodeling, and tooth root resorption, we performed a split-mouth model of OTM induced by a closed-coil spring stretched between the maxillary first molar and maxillary incisors in Ank KO and WT mice (including both males and females). Micro-computed tomographic analysis revealed a 36.6% reduction in OTM in Ank KO mice compared with WT mice, although OTM-induced thickening of PDL was found to be similar in both groups. While reduced tissue mineral density (TMD) of the alveolar bone was observed in WT mice, TMD in Ank KO mice was maintained. Loss of Ank leads to wider roots with thicker cementum on the untreated, contralateral side, whereas a significant increase in OTM-induced root resorption was observed on the lateral tension side. Histologic analysis of root resorption confirmed these data and showed increased resorption lacunae located prevalently in the OTM tooth root cementum of Ank KO mice. Using a quantitative PCR array of bone-associated markers to interrogate total RNA harvested from PDL tissues along the root surface, we found alterations in gene expression from OTM in both WT and Ank KO mice, which included genes involved in bone remodeling, calciotropic hormones and receptors, cytokines, growth factors, and receptors. Our findings advance the understanding of the role of Ank in regulating mineralization in the periodontium as well as factors involved in root resorption.