Inactivation of Sufu in cementoblasts accelerates external tooth root resorption.

Area of Science:

• Dental Biology
• Mineralized Tissue Biology
• Cell Signaling

Background:

• Cementum traditionally acts as an antiresorptive barrier for tooth roots.
• Mechanisms governing tooth root homeostasis and resistance to resorption remain incompletely understood.

Purpose of the Study:

• To investigate cementum factors and their interactions in preventing tooth root resorption.
• To elucidate the roles of ectonucleotide pyrophosphotase/phosphodiesterase 1 (Enpp1) and Hedgehog signaling in external cervical root resorption (ECRR).

Main Methods:

• Utilized transgenic mice models with targeted gene inactivation in cementoblasts.
• Employed cellular and molecular analyses, including studies with cementoblasts and bone marrow-derived macrophages.
• Investigated gene interactions using compound mutant mice.

Main Results:

• Functional inactivation of Enpp1 led to thickened cervical cementum susceptible to ECRR.
• Inactivation of suppressor of fused (Sufu) in cementoblasts induced ECRR, which was exacerbated by concurrent Sufu and Enpp1 inactivation.
• Dickkopf-related protein 1 (Dkk1), induced by Sufu inactivation, accelerated ECRR triggered by Enpp1 inactivation.
• Concurrent inactivation of Wntless and Enpp1 confirmed the synergistic role of Dkk1 and Npp1 in resorption.

Conclusions:

• Proper Enpp1 function is essential for maintaining tooth root homeostasis against resorption.
• Sustained Wnt activity in cervical cementum is critical for preventing physiological tooth root resorption.
• These findings highlight key molecular pathways regulating cementum's role in root integrity.