The Absence of Claudin-10 In the Enamel Organ Alters Its Integrity
Enamel, the hardest structure in the body, is affected throughout life by chronic or rare diseases. The study of the underlying pathological mechanisms has revealed new players in enamel formation. Among them, the disorders related to tight junction (TJ) proteins and kidney have been associated with impaired ameloblast function. Pathogenic variants of CLDN10, encoding claudin-10b, a cation transport channel, cause the autosomal recessive HELIX syndrome (Hypohidrosis, Electrolyte imbalance, hypoLacrymia, Ichthyosis, Xerostomia) in which patients experience disabling enamel wear. This study explored whether this premature enamel wear is due to intrinsic enamel fragility or xerostomia. In this purpose, we analyzed amelogenesis and enamel in several constitutive or conditional Cldn10 knockout (KO) murine models and human teeth. Our data show that claudin-10 was present in the cell membranes of the stratum intermedium, but not TJs, and that its absence disrupted signaling pathways related to ion transport and pH control. Although the ameloblasts still formed enamel, higher levels of aluminum were found in transplanted Cldn10 KO molars and in human HELIX enamel. These findings suggest that while xerostomia is the main cause of enamel wear, claudin-10 plays a key role in amelogenesis by regulating pH, and its deficiency leads to a loss of enamel organ integrity. Overall design: Microdissected ameloblasts (WT or KO claudin 10) and Microdissected Stratum intermedium cells (WT or KO claudin 10)