Optineurin Cooperates With NRF2 to Regulate Tooth Root Morphogenesis by Controlling Mitochondrial Dynamics and...

Area of Science:

• Developmental Biology
• Cell Biology
• Genetics

Background:

• Tooth root development is critical for function but poorly understood.
• Optineurin (OPTN), implicated in bone disorders, may influence tooth root formation.

Purpose of the Study:

• Investigate the role of Optineurin (OPTN) in tooth root development and odontoblast differentiation.
• Elucidate the molecular mechanisms by which OPTN regulates these processes.

Main Methods:

• Single-cell RNA sequencing of mouse and human developing teeth.
• In vitro studies using stem cells of the apical papilla (SCAPs) with OPTN downregulation.
• RNA-sequencing to analyze mitochondrial dynamics.
• Ex vivo organ cultures and in vivo gingival injections for rescue experiments.

Main Results:

• OPTN is essential for odontoblastic differentiation and proper root dentin formation.
• Optn knockout mice exhibit short roots, defective dentin, impaired apical papilla differentiation, and increased apoptosis.
• OPTN regulates mitochondrial dynamics, primarily promoting fission, which is crucial for differentiation and mineralization.
• OPTN interacts with NRF2 to control mitochondrial fission and BCL2 transcription.

Conclusions:

• OPTN is a key regulator of stem cells of the apical papilla (SCAPs) mitochondrial dynamics, mineralization, and apoptosis during tooth root development.
• The OPTN-NRF2 pathway is vital for maintaining tooth root morphogenesis.
• Findings offer new insights into the molecular basis of tooth root development and related disorders.