Dentin Matrix Protein 1 (DMP1) plays a regulatory role in dentin mineralization and can also function as a signaling molecule. MMP-2 (matrix metalloproteinase-2) is a predominant protease in the dentin matrix that plays a prominent role in tooth formation and a potential role during the carious process. The possibility that MMP-2 can cleave DMP1 to release biologically active peptides was investigated in this study. DMP1, both in the recombinant form and in its native state within the dentin matrix, was shown to be a substrate for MMP-2. Proteolytic processing of DMP1 by MMP-2 produced two major peptides, one that contains the C-terminal region of the protein known to carry both the ASARM (aspartic acid and serine rich domain) domain involved in biomineralization and the DNA binding site of DMP1. In vitro experiments with recombinant N-and C-terminal polypeptides mimicking the MMP-2 cleavage products of DMP1 demonstrated an effect of the C-polypeptide on the differentiation of dental pulp stem/progenitor cells to a putative odontoblast phenotype. In vivo implantation of this peptide in a rat injured pulp model induced a rapid formation of a homogeneous dentin bridge covered by a palisade of orientated cells expressing dentin sialoprotein (DSP) and DMP1, attesting an efficient repair process. These data suggest that a peptide generated through the proteolytic processing of DMP1 by MMP-2 can regulate the differentiation of mesenchymal cells during dentinogenesis and thus sustain reparative dentin formation in pathological situations such as carious decay. In addition, these data open a new therapeutic possibility of using this peptide to regenerate dentin after an injury.

X-linked hypophosphatemia (XLH) is a rare genetic disorder that disrupts skeletal and dental mineralization. In addition to rickets in children, XLH patients also have frequent spontaneous dental abscesses that increase the risk of tooth loss and may lead to facial cellulitis. Hypomineralized and hypoplastic dentin is the main driver of these infections. Conventional treatment (CT) of XLH improves this tissue defect and reduces the occurrence of dental abscesses. Burosumab is a recent treatment for XLH that targets excess circulating fibroblast growth factor 23 (FGF23), and its benefits on rickets have been demonstrated. It is not yet known whether burosumab improves dental manifestations of XLH. The main objective of our study was to compare the incidence of dental abscesses with XLH treated with either CT or burosumab. In this monocentric retrospective study, we measured and compared the incidence of dental abscess in children with XLH treated with either CT or burosumab, followed at our dental center for at least 1 year. The primary endpoint was the number of dental abscesses per month of dental follow-up. A total of 71 children were included in the study, with a mean AE standard deviation (SD) age at the start of dental follow-up of 7.86 AE 3.76. Thirty-eight children were treated with CT (53.5%) and 33 with burosumab (46.5%). All children treated with burosumab had previously been treated with CT. The mean number of dental abscesses per month of dental follow-up was significantly reduced in the burosumab group compared with the CT group (0.01 versus 0.04; p = 0.04). Burosumab treatment appears to be associated with a reduction in the number of dental abscesses in XLH children, compared with CT.