Primary cilia length stability is essential for dentinogenesis.

Abstract

Dentin, the primary hard tissue of teeth, is formed through the differentiation of dental mesenchymal progenitor cells into odontoblasts. Primary cilia, essential organelles on the surface of mesenchymal cell populations, are dynamically regulated in length and play a crucial role in dentinogenesis. However, the specific role of primary cilia length stability, in the regulation of cell function and dentin formation and repair, remains to be fully elucidated. Through spatial transcriptome analysis combined with mouse molar development studies, we found that ciliary membrane gene Arl13b specifically maintains cilia length homeostasis by suppressing cilia decapitation. ARL13B deficiency, which results in cilia shortening, would interfere with the differentiation fate of dental mesenchymal progenitor cells. Mechanistically, the abnormally shortened cilia disrupt intraflagellar transport-mediated SHH signaling within cilia, thereby inhibiting the odontoblastic differentiation, and ultimately affecting tertiary dentin formation during injury repair. These findings indicate that the maintenance of primary cilia length homeostasis is crucial for the repair and regeneration of dentin.