Cpt1a-Mediated Fatty Acid Oxidation Participates In Tooth Enamel Formation

Fatty acid oxidation (FAO) is closely involved in cell fate determination. Carnitine palmitoyltransferase 1A (CPT1A) is a key rate-limiting enzyme of FAO. This study aimed to explore the role of CPT1A-mediated FAO in enamel formation and dental epithelial cell fate determination. We conditionally knocked out Cpt1a in the epithelium of mice (cKO) to investigate its role in enamel formation. Enamel were analyzed using microCT, microhardness testing, SEM, H&E, and Masson staining. RNAseq was utilized to detect differentially expressed genes in cKO mice. TEM was used to detect mitochondrial morphology changes. CPT1A expression was increased and polarized during dental epithelial cell differentiation, indicating its potential role in enamel formation. H&E and Masson staining revealed disordered ameloblast arrangement, vacuolar degeneration, and enamel formation defects in cKO mice. Enamel thickness and hardness were significantly reduced in cKO mice incisors and molars, with SEM demonstrating disorganized enamel columns. Immunofluorescence revealed decreased CPT1A and amelogenin expression, and increased proliferating cells in cKO mice. RNAseq showed genes related to mitochondrial dynamics (PGC-1α, Opa1, Drp-1) were elevated. TEM analysis validated that the number of mitochondria in CKO mice was increased, accompanied by active fission and fusion. CPT1A-mediated FAO regulated the proliferation and differentiation of dental epithelial cells to participate in enamel formation, potentially by influencing mitochondrial function and dynamic.