Compression force regulates cementoblast mineralization via S1PR1/mitophagy axis

Area of Science:

• Biomedical Engineering
• Cell Biology
• Orthodontics

Background:

• Orthodontically induced inflammatory root resorption (OIIRR) is a clinical issue caused by excessive orthodontic force.
• Cementoblasts are crucial for cementum mineralization and resorption resistance, but their function is impaired by orthodontic forces.
• The role of mitophagy in cementoblast response to orthodontic force is not well understood.

Purpose of the Study:

• To investigate the role of the S1PR1/mitophagy axis in cementoblast mineralization and OIIRR.
• To explore the molecular mechanisms linking orthodontic force, cementoblast function, and root resorption.

Main Methods:

• Utilized an in vivo orthodontic loading model to induce OIIRR and assess cementoblast mineralization.
• Employed in vitro experiments with OCCM30 cells to analyze reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and mitophagy.
• Investigated the effects of S1PR1 modulation and pharmacological activation (SEW2871) on cementoblasts and OIIRR.

Main Results:

• Heavy orthodontic compression suppressed mitophagy in cementoblasts by downregulating PINK1 and PARKIN.
• In vitro, compression increased ROS, disrupted MMP, and inhibited mitophagy, impairing cementoblast mineralization.
• S1PR1 upregulation activated mitophagy, restoring cementoblast mineralization, and SEW2871 treatment alleviated OIIRR in vivo.

Conclusions:

• The S1PR1/mitophagy axis is critical for maintaining cementoblast function and mineralization under orthodontic force.
• Dysregulation of this axis contributes to OIIRR.
• Targeting the S1PR1/mitophagy pathway presents a potential therapeutic strategy to prevent OIIRR.