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An endoplasmic reticulum stress regulator, Tmbim6, modulates secretory stage of mice molar
Yam Prasad Aryal1, Sanjiv Neupane1, Nirpesh Adhikari1
1Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Korea.
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.
Insights
Endoplasmic reticulum (ER) stress, modulated by Tmbim6, is crucial for patterned dental hard tissue formation in mice molars. Tmbim6 deficiency alters enamel and dentin development, impacting mineral content and ultrastructure.
Area of Science:
- Biochemistry
- Developmental Biology
- Cell Biology
Background:
- Endoplasmic reticulum (ER) stress is implicated in various biological processes.
- The unfolded protein response (UPR) is a key pathway activated by ER stress.
- Tmbim6 is known to antagonize the UPR.
Purpose of the Study:
- To investigate the role of Tmbim6 in mice molar development.
- To elucidate the involvement of ER stress in dental hard tissue formation.
- To understand the impact of Tmbim6 deficiency on enamel and dentin development.
Main Methods:
- Utilized Tmbim6 knockout (KO) mice models.
- Employed in vitro organ cultivation techniques.
- Performed small interfering RNA (siRNA) knockdown of Tmbim6.
- Analyzed gene expression (Dspp, AMELX), protein localization, Bmp signaling, proliferation, and actin rearrangement.
Main Results:
- Tmbim6 is expressed during critical stages of mice molar development (E14-E16, PN0, PN6).
- Tmbim6 KO mice exhibited reduced enamel mineral content and altered dentin structure.
- Observed changes in odontoblast differentiation, Dspp expression, and AMELX localization.
- In vitro studies confirmed altered Bmp signaling, proliferation, and actin dynamics.
Conclusions:
- ER stress, influenced by Tmbim6, plays a significant role in patterned dental hard tissue formation.
- Tmbim6 deficiency leads to ultrastructural and compositional changes in enamel and dentin.
- Modulation of ER stress is critical during specific developmental windows for proper tooth formation.
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