An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar

Abstract

To understand the role of endoplasmic reticulum (ER)-stress in mice molar development, we studied Tmbim6 that antagonizes the unfolded protein response, using Tmbim6 knockout (KO) mice and in vitro organ cultivation with knocking down using small interfering RNA. During molar development, Tmbim6 is expressed in developing tooth at E14-E16, postnatal0 (PN0), and PN6. Mineral content in Tmbim6 KO enamel was reduced while dentin was slightly increased revealing ultrastructural changes in pattern formation of both enamel and dentin. Moreover, odontoblast differentiation was altered with increased Dspp expression at PN0 followed by altered AMELX localizations at PN5. These results were confirmed by in vitro organ cultivation and showed altered Bmp signaling, proliferation, and actin rearrangement in the presumptive ameloblast and odontoblasts that followed the altered expression of differentiation and ER stress-related signaling molecules at E16.5. Overall, ER stress modulated by Tmbim6 would play important roles in patterned dental hard tissue formation in mice molar within a limited period of development. K E Y W O R D Samelogenesis, dentinogenesis, ER stress, molar development, Tmbim6 knockout

Facilitation of Reparative Dentin Using a Drug Repositioning Approach With 4-Phenylbutric Acid

“…In this study, we hypothesized that in the exposed dentin and pulp complex, ER stress would be occurred unavoidably to repair the dentin structure and maintain the vitality of the pulp as examined in other wound sites 17,19,20 . In in ammation condition, a number of studies revealed the vicious circle of escalation of pathological conditions between ER stress and in ammation responses 26,37 .…”

“…Formation of dentin is mainly contributed by cellular physiology of odontoblasts. These speci c secreting cells are precisely regulated and modulated by ER regulation and vesicle tra cking to form the speci cally featured dentin matrices through protein synthesis, folding, tra cking, secretion, and patterned apposition 17,19,20 . Previous studies reported that modulation of ER stress would be an important cellular pathway for differentiation and maintenance of dentin 18,31 .…”

“…Several previous reports suggested that ER stress would affects formation of dentin. When ER stress regulator gene, Tmbim6 was knocked out, the dentin and enamel structures were disturbed by altering odontoblast and enamel differentiation 17 . Mutated dentin forming genes of which could cause Dentinogenesis Imperfecta and dentin dysplasia may cause a high level of ER stress [18][19][20] .…”

Resveratrol enhances bone formation by modulating inflammation in the mouse periodontitis model

“…ImageJ software was used to quantify all morphologic data as described previously. 31 At least three different figures from three different samples were used for the statistical analysis.…”

Facilitation of Reparative Dentin Using a Drug Repositioning Approach With 4-Phenylbutric Acid

“…Previous report suggested that ER stress would affect formation of dentin. For instance: when ER stress regulator gene, Tmbim6 was knocked out, the dentin and enamel structures were disturbed by altering odontoblast and enamel differentiation ( Aryal et al, 2019 ). Mutated dentin forming genes of which could cause Dentinogenesis Imperfecta and Dentin Dysplasia may cause a high level of ER stress ( Brookes et al, 2014 ; Brookes et al, 2017 ; Liang et al, 2019 ).…”