Transcriptome analysis of ankylosed primary molars with infraocclusion

Annie Tong,Seong-Seng Tan,Yuh-Lit Chow,Katie Xu,Paul Schneider,Rita Hardiman

doi:10.1038/s41368-019-0070-1

Abstract

Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded (n = 7) and non-infraoccluded (n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432 (2.3%) genes were differentially expressed between the two groups (false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez; tissues that are central to the ankylotic process. We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.

Highlights

Dental ankylosis is defined as a fusion of cementum or dentine with alveolar bone.[1]
periodontal ligament (PDL) space mineralization and dental ankylosis have been observed in animals with altered bone metabolism, for example in mutant mice with elevated Wnt signalling,[12] in osteopetrotic mutant rabbits with reduced osteoclast-mediated bone resorption,[13] and in mice injected with bisphosphonate.[14]
DE genes in bone tissue After excluding genes with low counts, 18 529 genes were retained for further analysis, from which 432 genes (2.3%) were found to be differentially expressed between the two groups (false discovery rate (FDR) < 0.05) (Supplementary Table 1)

Summary

Introduction

Dental ankylosis is defined as a fusion of cementum or dentine with alveolar bone.[1]. Despite the abundance of clinical and epidemiological data, little is known about the molecular correlates of primary molar ankylosis. Genetic associations have been proposed, mostly based on epidemiological data from familial, ethnicity, and dental anomaly pattern studies.[5,6,7,8,9,10] despite compelling evidence for strong familial and ethnic associations, no candidate genes or molecular pathways have been identified. In a staining study, bone from ankylosed human primary molars demonstrated no difference in the expression of NADH-diaphorase, acid phosphatase, and alkaline phosphatase.[16]

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Conclusion