Implications for novel drug development in bone metabolism: Beyond the dentin extracellular matrix.

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In this study, we examined the effects of dentin sialophosphoprotein (DSPP), one of the major extracellular matrix proteins in dentin, on bone turnover in vivo and in vitro. According to micro CT analysis, DSPP knock out (KO) mouse femora showed significantly decreased bone mineral density as compared to those in DSPP wild type (WT) mice. However, calvarial organ culture analysis revealed that the decreased osteoclastogenesis in DSPP KO as compared to WT calvaria. Using bone marrow stromal cells (BMSCs) isolated from both WT and KO mice, we found that under the osteogenic media,ALP activity and in vitro mineralization were higher in BMSCs derived from WT mice as compared to those from KO mice. On the other hand, the KO derived BMSCs showed increased differentiation into adipocytes as compared to those from WT mice. Thus, the DSPP may be a positive regulator for the bone mineral density, promoting the bone formation but not suppressing the bone resorption.