Energy metabolic shift contributes to the phenotype modulation of maturation stage ameloblasts

Haruno Arai; Akira Inaba; Shojiro Ikezaki; Mika Kumakami-Sakano; Marii Azumane; Hayato Ohshima; Kazumasa Morikawa; Hidemitsu Harada; Keishi Otsu

doi:10.3389/fphys.2022.1062042

Energy metabolic shift contributes to the phenotype modulation of maturation stage ameloblasts

Front Physiol. 2022 Nov 29:13:1062042. doi: 10.3389/fphys.2022.1062042. eCollection 2022.

Authors

Haruno Arai^{1

2}, Akira Inaba^{1

2}, Shojiro Ikezaki¹, Mika Kumakami-Sakano¹, Marii Azumane^{1

3}, Hayato Ohshima⁴, Kazumasa Morikawa², Hidemitsu Harada¹, Keishi Otsu¹

Affiliations

¹ Division of Developmental Biology and Regenerative Medicine, Department of Anatomy, Iwate Medical University, Yahaba, Japan.
² Division of Pediatric and Special Care Dentistry, Department of Oral Health Science, School of Dentistry, Iwate Medical University, Morioka, Japan.
³ Division of Oral and Maxillofacial Surgery, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University, Morioka, Japan.
⁴ Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Abstract

Maturation stage ameloblasts (M-ABs) are responsible for terminal enamel mineralization in teeth and undergo characteristic cyclic changes in both morphology and function between ruffle-ended ameloblasts (RA) and smooth-ended ameloblasts (SA). Energy metabolism has recently emerged as a potential regulator of cell differentiation and fate decisions; however, its implication in M-ABs remains unclear. To elucidate the relationship between M-ABs and energy metabolism, we examined the expression pattern of energy metabolic enzymes in M-ABs of mouse incisors. Further, using the HAT7 cell line with M-AB characteristics, we designed experiments to induce an energy metabolic shift by changes in oxygen concentration. We revealed that RA preferentially utilizes oxidative phosphorylation, whereas SA depends on glycolysis-dominant energy metabolism in mouse incisors. In HAT7 cells, hypoxia induced an energy metabolic shift toward a more glycolytic-dominant state, and the energy metabolic shift reduced alkaline phosphatase (ALP) activity and calcium transport and deposition with a change in calcium-related gene expression, implying a phenotype shift from RA to SA. Taken together, these results indicate that the energy metabolic state is an important determinant of the RA/SA phenotype in M-ABs. This study sheds light on the biological significance of energy metabolism in governing M-ABs, providing a novel molecular basis for understanding enamel mineralization and elucidating the pathogenesis of enamel hypomineralization.

Keywords: OxPhos; ameloblast; enamel; energy metabolism; glycolysis; hypoxia; mineralization; tooth.