Deficiency of Trps1 in Cementoblasts Impairs Cementogenesis and Tooth Root Formation.

Abstract

Cementum is the least studied of all mineralized tissues and little is known about mechanisms regulating its formation. Therefore, the goal of this study was to provide new insights into the transcriptional regulation of cementum formation by determining the consequences of the deficiency of the Trps1 transcription factor in cementoblasts. We used Trps1^Col1a1 cKO (2.3Co1a1-Cre^ERT2;Trps1^fl/fl) mice, in which Trps1 is deleted in cementoblasts. Micro-computed tomography analyses of molars of 4-week-old males and females demonstrated significantly shorter roots with thinner mineralized tissues (root dentin and cementum) in Trps1^Col1a1 cKO compared to WT mice. Semi-quantitative histological analyses revealed a significantly reduced area of cellular cementum and localized deficiencies of acellular cementum in Trps1^Col1a1 cKO mice. Immunohistochemical analyses revealed clustering of cementoblasts at the apex of roots, and intermittent absence of cementoblasts on Trps1^Col1a1 cKO cementum surfaces. Fewer Osterix-positive cells adjacent to cellular cementum were also detected in Trps1^Col1a1 cKO compared to WT mice. Decreased levels of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme required for proper cementogenesis, were apparent in cementum, periodontal ligament, and alveolar bone of Trps1^Col1a1 cKO. There were no apparent differences in levels of bone sialoprotein (Bsp) in cementum. Quantitative analyses of picrosirius red-stained periodontal ligament revealed shorter and disorganized collagen fibers in Trps1^Col1a1 cKO mice demonstrating impaired periodontal structure. In conclusion, this study has identified Trps1 transcription factor as one of the important regulators of cellular and acellular cementum formation. Furthermore, this study suggests that Trps1 supports the function of cementoblasts by upregulating expression of the major proteins required for cementogenesis, such as Osterix and TNAP.