Oral Dis. 2015 May 6. doi: 10.1111/odi.12347. [Epub ahead of print]
CCN2/CTGF expression via cellular uptake of BMP-1 is associated with reparative dentinogenesis.
Muromachi K1,2, Kamio N2, Matsuki-Fukushima M3, Nishimura H4, Tani-Ishii N1, Sugiya H5, Matsushima K2,6.
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Abstract
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.
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
KEYWORDS:
BMP-1; CCN2/CTGF; Endocytosis; dental pulp; reparative dentinogenesis
PMID:
25944709