Reduced orthodontic tooth movement in Ank knockout mice

JBMR Plus, vol. 9, pp. ziaf064

Abstract

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.

Authors 9

1. Marta Rizk corresponding Aachen Department of Orthodontics

   Universitätsklinikum Aachen

   Affiliation as printed

   Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,

2. Emily Y. Chu

   University of Maryland, Baltimore

   Affiliation as printed

   Department of Biomaterials and Regenerative Dental Medicine, University of Maryland School of Dentistry , Baltimore, MD 21201-1786 ,

3. Rogerio Bastos Craveiro Aachen Department of Orthodontics

   Universitätsklinikum Aachen

   Affiliation as printed

   Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,

4. Sihem Brenji Aachen Department of Orthodontics

   Universitätsklinikum Aachen

   Affiliation as printed

   Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,

5. Christian Niederau Aachen Department of Orthodontics

   Universitätsklinikum Aachen

   Affiliation as printed

   Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,

6. Nikolaus Marx Aachen Department of Internal Medicine I-Cardiology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine I—Cardiology, Angiology and Intensive Care Medicine, University Hospital RWTH Aachen , Aachen 52074 ,

7. Brian Lee Foster

   The Ohio State University

   Affiliation as printed

   Division of Biosciences, College of Dentistry, The Ohio State University , Columbus, OH 43210-1267 ,

8. Martha Joan Somerman

   National Institutes of Health · National Institute of Arthritis and Musculoskeletal and Skin Diseases

   Affiliation as printed

   National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health , Bethesda, MD 20892-3675 ,

9. Michael F. Wolf Aachen Department of Orthodontics

   Universitätsklinikum Aachen

   Affiliation as printed

   Department of Orthodontics, University Hospital Aachen , Aachen 52074 ,