MEPE Localization in the Craniofacial Complex and Function in Tooth Dentin Formation

Abstract

Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein found in dental and skeletal tissues. Although information regarding the role of MEPE in bone and disorders of phosphate metabolism is emerging, the role of MEPE in dental tissues remains unclear. We performed RNA in situ hybridization and immunohistochemistry analyses to delineate the expression pattern of MEPE during embryonic and postnatal development in craniofacial mineralizing tissues. Mepe RNA expression was seen within teeth from cap through root formation in association with odontoblasts and cellular cementoblasts. More intense expression was seen in the alveolar bone within the osteoblasts and osteocytes. MEPE immunohistochemistry showed biphasic dentin staining in incisors and more intense staining in alveolar bone matrix and in forming cartilage. Analysis of Mepe null mouse molars showed overall mineralized tooth volume and density of enamel and dentin comparable with that of wild-type samples. However, Mepe(-/-) molars exhibited increased thickness of predentin, dentin, and enamel over controls and decreased gene expression of Enam, Bsp, Dmp1, Dspp, and Opnby RT-PCR. In vitro Mepe overexpression in odontoblasts led to significant reductions in Dspp reporter activity. These data suggest MEPE may be instrumental in craniofacial and dental matrix maturation, potentially functioning in the maintenance of non-mineralized matrix.

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

“…Among genes harboring an excess of HF SNCs associated with specific facial features, we find RUNX2 , EDAR , and GLI3 133 , NFATC1 134 , SPOP 135 , DDR2 136 and NELL1 137 , possibly carrying changes in regulatory regions, while mutations in the HHMC-carrying gene encoding for the transcription factor ATRX cause facial dysmorphism 138 . In addition, genes with HHMCs such as PLXNA2 139 , EVC2 140 , MEPE 141 , OMD 142 , and SPAG17 143 are known to affect craniofacial bone and tooth morphologies. These genes appear to be important in determining bone density, mineralization and remodeling, hence they may underlie differences between archaic and modern human facial growth 144 .…”

Overlapping functions of bone sialoprotein and pyrophosphate regulators in directing cementogenesis

“…Loss of either Dspp or Dmp1 in mice causes changes in acellular cementum, however it remains unclear if this is due to a direct role of the associated proteins in cementogenesis, or indirect effects of wider changes in the periodontium or mineral metabolism [26, 93–95]. While MEPE has been shown to regulate skeletal mineralization, its role in dental development has only been recently investigated, implicating the protein in dentinogenesis and amelogenesis, whereas its role in cementum formation remains undefined [96]. …”

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

“…RUNX2, EDAR, and GLI3(Adhikari et al 2016), NFATC1(Kim and Kim 2014), SPOP(Cai and Liu 2016), DDR2) and NELL1, possibly carrying changes in regulatory regions, while mutations in the HHMC-carrying gene encoding for the transcription factor ATRX cause facial dysmorphism(Moncini et al 2013). In addition, genes with HHMCs such as PLXNA2(Oh et al 2012), EVC2(Kwon et al 2018), MEPE(Gullard et al 2016), OMD(Tashima et al 2015), and SPAG17(Teves et al 2015) are known to affect craniofacial bone and tooth morphologies. These genes appear to be important in determining bone density, mineralization…”