Trps1 transcription factor regulates mineralization of dental tissues and proliferation of tooth organ cells

Abstract

Mutations of the TRPS1 gene cause trichorhinophalangeal syndrome (TRPS), a skeletal dysplasia with dental abnormalities. TRPS dental phenotypes suggest that TRPS1 regulates multiple aspects of odontogenesis, including the tooth number and size. Previous studies delineating Trps1 expression throughout embryonic tooth development in mice detected strong Trps1 expression in dental mesenchyme, preodontoblasts, and dental follicles, suggesting that TRPS dental phenotypes result from abnormalities in early developmental processes. In this study, Trps1 +/− and Trps1 −/− mice were analyzed to determine consequences of Trps1 deficiency on odontogenesis. We focused on the aspects of tooth formation that are disturbed in TRPS and on potential molecular abnormalities underlying TRPS dental phenotypes. Microcomputed tomography analyses of molars were used to determine tooth size, crown shape, and mineralization of dental tissues. These analyses uncovered that disruption of one Trps1 allele is sufficient to impair mineralization of dentin in both male and female mice. Enamel mineral density was decreased only in males, while mineralization of the root dental tissues was decreased only in females. In addition, significantly smaller teeth were detected in Trps1 +/− females. Histomorphometric analyses of tooth organs showed reduced anterior-posterior diameter in Trps1 −/− mice. BrdU-incorporation assay detected reduced proliferation of mesenchymal and epithelial cells in Trps1 −/− tooth organs.Immunohistochemistry for Runx2 and Osx osteogenic transcription factors revealed changes in their spatial distribution in Trps1 −/− tooth organs and uncovered cell-type specific requirements of Trps1 for Osx expression. In conclusion, this study has demonstrated that Trps1 is a positive regulator of cell proliferation in both dental mesenchyme and epithelium, suggesting that the microdontia in TRPS is likely due to decreased cell proliferation in developing tooth organs. Furthermore, the reduced mineralization observed in Trps1 +/− mice may provide some explanation for the extensive dental caries reported in TRPS patients.

Expression and function of the P2X7 receptor in human osteoblasts: The role of NFATc1 transcription factor

“…The bioinformatic analysis we performed suggests that it is reasonable to further investigate the role performed by other factors such as RUNX2, TRPS1, HIF‐1, or TCF/β‐catenin in the regulation of P2RX7 expression, for the reasons mentioned below. RUNX2 is the master regulator of osteogenesis (Vimalraj, Arumugam, Miranda, & Selvamurugan, 2015), and TRPS1 has been recently correlated with the mineralization process (Goss et al, 2019). In addition, low oxygen tension is the physiological condition of the bones, and it leads to an increased expression of HIF‐1α.…”

Spontaneous Development of Dental Dysplasia in Aged Parp-1 Knockout Mice

“…In this study, only male mice were analyzed because it was preferred to analyze the effect of Parp-1 deficiency on dental differentiation at an advanced age in the absence of the effect of the estrous cycle. However, a gender difference of tooth formation has been reported using Trps1 +/− (trichorhinophalangeal syndrome heterozygous) mice showing significantly smaller crown and root volumes in female Trps1 +/− mice compared with male Trps1 +/− mice [31]. Trichorhinophalangeal syndrome is a skeletal dysplasia with skeletal defects as well as dental abnormalities, where Trps1 gene regulates dental mineralization.…”

Features of the Course of Enamel Biomineralization Processes in Various Anatomical Areas of the Tooth

“…According to modern research, octacalcium phosphate is a precursor of biological mineralization. In electron microscopic examination, calcium octaphosphate particles consist of thin plates, several nanometers in size, which resemble light, thin filamentary structures on the scanned sections, intertwined in the form of sockets [7,8].…”

“…The functional feature of the epithelial lining is the adsorption from salivary fluid of periodontal fluid and deposition of protein masses on the surface of the epithelium [8,15,16]. Sometimes minerals form white granular masses that are located in the gingival sulcus [7,17,18].…”