CCN2/CTGF expression via cellular uptake of BMP‐1 is associated with reparative dentinogenesis

Objective CCN family member 2/connective tissue growth factor (CCN2/CTGF) is known as an osteogenesis-related molecule and is thought to be implicated in tooth growth. Bone morphogenetic protein-1 (BMP-1) contributes to tooth development by the degradation of dentin-specific substrates as a metalloprotease. In this study, we demonstrated the correlations between CCN2/CTGF and BMP-1 in human carious teeth and the subcellular dynamics of BMP-1 in human dental pulp cells. Materials and Methods Expression of CCN2/CTGF and BMP-1 in human carious teeth was analyzed by immunohistochemistry. BMP-1-induced CCN2/CTGF protein expression in primary cultures of human dental pulp cells was observed by immunoblotting. Intracellular dynamics of exogenously administered fluorescence-labeled BMP-1 were observed using confocal microscope. Results Immunoreactivities for CCN2/CTGF and BMP-1 were increased in odontoblast-like cells and reparative dentin-subjacent dental caries. BMP-1 induced the expression of CCN2/CTGF independently of protease activity in the cells but not that of dentin sialophosphoprotein (DSPP) or dentin matrix protein-1 (DMP-1). Exogenously added BMP-1 was internalized into the cytoplasm, and the potent dynamin inhibitor dynasore clearly suppressed the BMP-1-induced CCN2/CTGF expression in the cells. Conclusion CCN2/CTGF and BMP-1 coexist beneath caries lesion and CCN2/CTGF expression is regulated by dynamin-related cellular uptake of BMP-1, which suggests a novel property of metalloprotease in reparative dentinogenesis.