Roles of calcium in ameloblasts during tooth development: A scoping review

Objectives: Calcium ions (Ca2 & thorn;) play crucial role in tooth development, particularly in maintaining enamel density during amelogenesis. Ameloblasts require specific proteins such as amelogenin, ameloblastin, enamelin, kallikrein, and collagen for enamel growth. Recent research has highlighted the importance of calcium and fluoride ions, as well as the TRPM7, STIM, and SOCE pathways, in regulating various stages of enamel formation. This review synthesizes current knowledge, focusing on pre- clinical data elucidating the molecular mechanisms of calcium transport in ameloblasts, during normal tooth development and in response to external stimuli. Methods: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search, conducted in December 2023, spanned multiple databases including PubMed (8.363 records), Google Scholar (5.630 records), and Science Direct (21.810 records). The primary aim was to examine the influence of calcium ion regulation on ameloblast development, with a focus on preclinical studies. Results: After an initial screening of 396 titles and abstracts, 11 full-text articles (four in vitro studies and seven animal studies) met the inclusion and exclusion criteria. The studies, assessed for quality using the CAMRADES tool, ranged from low to moderate. Calcium deficiency, nutritional supplements, fluoride exposure, TRPM7, STIM proteins, and the SOCE pathway were found to influence amelogenesis. Conclusion: Calcium transport mechanisms play a critical role in enamel formation, with factors such as TRPM7, Kir 4.2, CRAC channels, and the SOCE pathway supporting enamel mineralization, while disruptions like hypoxia, fluoride exposure, and circadian imbalances negatively impact amelogenesis. Understanding the interplay between calcium, environmental, and nutritional factors provides valuable insights into ameloblast function and offers potential avenues for improving enamel quality and addressing defects.