Dual Role of the Trps1 Transcription Factor in Dentin Mineralization [Gene Regulation]

August 15th, 2014 by Kuzynski, M., Goss, M., Bottini, M., Yadav, M. C., Mobley, C., Winters, T., Poliard, A., Kellermann, O., Lee, B., Millan, J. L., Napierala, D.

TRPS1 is a unique GATA-type transcription factor that acts as a transcriptional repressor. TRPS1 deficiency (tricho-rhino-phalangeal syndrome, TRPS) and dysregulated TRPS1 expression (Ambras syndrome) result in skeletal and dental abnormalities implicating TRPS1 in endochondral bone formation and tooth development. Moreover, TRPS patients frequently present with low bone mass indicating TRPS1 involvement in bone homeostasis. In addition, our previous data demonstrated accelerated mineralization of the perichondrium in Trps1 mutant mice and impaired dentin mineralization in Col1a1-Trps1 transgenic mice, implicating Trps1 in the mineralization process. To understand the role of Trps1 in the differentiation and function of cells producing mineralized matrix, we used a preodontoblastic cell line as a model of dentin mineralization. We generated both Trps1-deficient and Trps1-overexpressing stable cell lines, and analyzed the progression of mineralization by alkaline phosphatase and alizarin red staining. As predicted, based on our previous in vivo data, delayed and decreased mineralization of Trps1-overexpressing odontoblastic cells was observed when compared to control cells. This was associated with downregulation of genes regulating phosphate homeostasis. Interestingly, Trps1-deficient cells lost the ability to mineralize and demonstrated decreased expression of several genes critical for initiating the mineralization process, including Alpl and Phospho1. Based on these data we have concluded that Trps1 serves two critical and context-dependent functions in odontoblast-regulated mineralization: 1) Trps1 is required for odontoblast maturation by supporting expression of genes crucial for initiating the mineralization process, 2) Trps1 represses the function of mature cells and, consequently, restricts the extent of extracellular matrix mineralization.