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

在本研究中，我们研究了牙本质中主要的细胞外基质蛋白之一牙本质唾液磷蛋白（DSPP）对体内和体外骨转换的影响。微CT分析显示，DSPP敲除（KO）小鼠股骨骨密度较DSPP野生型（WT）小鼠明显降低。然而，颅骨器官培养分析显示，与WT颅骨相比，DSPP KO的破骨细胞生成减少。使用从WT和KO小鼠分离的骨髓基质细胞（BMSCs），我们发现在成骨培养基下，WT小鼠的BMSCs的ALP活性和体外矿化高于KO小鼠。另一方面，与来自WT小鼠的骨髓间充质干细胞相比，KO衍生的骨髓间充质干细胞向脂肪细胞的分化增加。因此，DSPP可能是骨矿物质密度的积极调节剂，促进骨形成但不抑制骨吸收。

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.