Preprint Article Version 1 This version is not peer-reviewed

ADAM10 Expression by Ameloblasts is Essential for Proper Enamel Formation

Version 1 : Received: 10 October 2024 / Approved: 11 October 2024 / Online: 11 October 2024 (17:03:47 CEST)

How to cite: Shahid, S.; Hu, Y.-Y.; Mohamed, F.; Rizzotto, L.; Layana, M. C.; Fleming, D. T.; Papagerakis, P.; Foster, B. L.; Simmer, J. P.; Bartlett, J. D. ADAM10 Expression by Ameloblasts is Essential for Proper Enamel Formation. Preprints 2024, 2024100930. https://doi.org/10.20944/preprints202410.0930.v1 Shahid, S.; Hu, Y.-Y.; Mohamed, F.; Rizzotto, L.; Layana, M. C.; Fleming, D. T.; Papagerakis, P.; Foster, B. L.; Simmer, J. P.; Bartlett, J. D. ADAM10 Expression by Ameloblasts is Essential for Proper Enamel Formation. Preprints 2024, 2024100930. https://doi.org/10.20944/preprints202410.0930.v1

Abstract

ADAM10 is a multi-functional proteinase that can cleave approximately 100 different substrates. Previously, we demonstrated that ADAM10 is expressed by ameloblasts responsible for enamel formation. Here we asked if ADAM10 plays a role in enamel development. Deletion of Adam10 in mice is embryonic lethal and deletion of Adam10 from epithelia is perinatal lethal. We therefore deleted Adam10 from ameloblasts. Here, we confirm ameloblast-specific expression of the Tg(Amelx-iCre)872pap construct. We crossed these mice with Adam10 floxed mice to generate Amelx-iCre; Adam10fl/fl mice (Adam10 cKO). We show that Adam10 cKO mice have discolored teeth with softer than normal enamel. Notably, the Adam10 cKO enamel density and volume were significantly reduced in both incisors and molars. Moreover, the incisor enamel rod pattern became progressively more disorganized moving from the DEJ to the outer enamel surface and this disorganized rod structure created large gaps between and among the rods. ADAM10 cleaves proteins essential for cell signaling and for enamel formation such as RELT and COL17A1. ADAM10 also cleaves cell-cell contacts such as E- and N-cadherins that may support ameloblast movement necessary for normal rod patterns. Here, we show for the first time that ADAM10 expressed by ameloblasts is essential for proper enamel formation.

Keywords

ameloblast migration; Cre Lox recombination; occlusal enamel; cervical enamel; density; hardness; volume; mouse

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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