Genetic evidence for key roles of decorin and biglycan in dentin mineralization.

Genetic evidence for key roles of decorin and biglycan in dentin mineralization.
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DOI:
10.1016/j.matbio.2009.01.005
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发表时间:
2009-04
期刊:
影响因子:
6.9
通讯作者:
Kulkarni, Ashok B.
Kulkarni, Ashok B.
中科院分区:
生物学1区
文献类型:
--
作者:
Haruyama, Naoto;Sreenath, Taduru L.;Suzuki, Shigeki;Yao, Xiaomei;Wang, Zhigang;Wang, Yong;Honeycutt, Cherlita;Iozzo, Renato V.;Young, Marian F.;Kulkarni, Ashok B.

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小鼠牙本质涎磷蛋白(DSPP)基因的靶向阻断(DSPP−/−)导致牙本质矿化缺陷,其扩大的前牙本质表型类似于人牙本质形成不全III型。利用DSPP/Biglycan(Dspp−/−Bgn−/0)和DSPP/Decorin(Dspp−/−Dcn−/−)双基因敲除小鼠,我们确定Dspp−/−中扩大的前牙本质层在没有核心蛋白的情况下可以被挽救,但在没有Biglycan的情况下不能。然而,傅里叶变换红外光谱分析显示,Dspp−/−BGN−/0和Dspp−/−DCN−/−牙齿的牙本质矿化程度相似。原子力显微镜(AFM)对牙本质中胶原纤维的分析表明,这些基因型的胶原纤维形态有细微的差异。Dspp−/−Dcn−/−中扩大的前牙本质减少,提示Dspp−/−前牙本质中核心蛋白聚糖水平的升高干扰了牙本质矿化前沿的矿化过程。另一方面,DSPP和Biglycan的缺乏导致DSPP−/−BGN−/0前牙本质中钙球的数量增加,这表明与DSPP−/−−/0相比,DSPP−/−BGN BGN/0的钙球结合失败更严重。这些发现表明,富含亮氨酸的小分子蛋白多糖的正常表达在牙本质矿化的高度协调过程中发挥着重要作用。
Targeted disruption of the dentin sialophosphoprotein (DSPP) gene in the mice (Dspp−/−) results in dentin mineralization defects with enlarged predentin phenotype similar to human dentinogenesis imperfecta type III. Using DSPP/biglycan (Dspp−/−Bgn−/0) and DSPP/decorin (Dspp−/−Dcn−/−) double knockout mice, here we determined that the enlarged predentin layer in Dspp−/− is rescued in the absence of decorin, but not in the absence of biglycan. However, Fourier transform infrared (FTIR) spectroscopy analysis reveals similar hypomineralization of dentin in both Dspp−/−Bgn−/0 and Dspp−/−Dcn−/− teeth. Atomic force microscopy (AFM) analysis of collagen fibrils in dentin shows subtle differences in the collagen fibril morphology of these genotypes. The reduction of enlarged predentin in Dspp−/−Dcn−/− suggests that the elevated level of decorin in Dspp−/− predentin interferes with the mineralization process at the dentin mineralization front. On the other hand, the lack of DSPP and biglycan leads to the increased number of calcospherites in Dspp−/−Bgn−/0 predentin, suggesting that a failure in coalescence of calcospherites was augmented in Dspp−/−Bgn−/0 as compared to Dspp−/− teeth. These findings indicate that normal expression of small leucine rich proteoglycans, such as biglycan and decorin, plays an important role in the highly orchestrated process of dentin mineralization.
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