长期给药羟基乙基二膦酸酯(HEBP)对大鼠牙本质基质蛋白的影响。

Y. Wada, R. Fujisawa, Y. Kuboki
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摘要

双膦酸盐被广泛认为是矿化组织形成和吸收的抑制剂。然而,双膦酸盐如何影响矿化组织中磷酸钙沉淀和基质合成尚不确定。已有几种组织学方法用于研究受双膦酸盐影响的硬组织。在本研究中,我们用一种双膦酸盐进行生化研究,研究生物矿化的机制,并考虑双膦酸盐的作用。大鼠皮下注射1,1 -二膦酸羟乙基二烯(HEBP) 10mg P/kg,连续7周。取大鼠切牙,生化分析牙本质基质蛋白。实验大鼠门牙基质蛋白含量相对增加,但与对照大鼠相比,矿化程度有所降低。实验大鼠牙本质特有的磷酸化蛋白——牙本质磷酸化蛋白也明显升高。然而,牙本质的其他非胶原蛋白的组成基本没有改变。双膦酸盐对矿化的抑制作用可能不是通过抑制非胶原基质蛋白的合成来实现的,而主要是通过抑制磷酸钙沉积来实现的。此外,该处理可能促进了磷蛋白的合成。
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Changes of the Rat Dentin Matrix Proteins Affected by Long-term Administration of Hydroxyethylidene-1,1-bisphosphonate (HEBP).
Bisphosphonates are widely known as inhibitors of formation and resorption of mineralized tissues. However, it is uncertain how bisphosphonates affect calcium phosphate precipitation and matrix synthesis in mineralized tissues. Several histological approaches have been done to study hard tissues affected by bisphosphonates. In this study, we used a bisphosphonate for biochemical investigation to study the mechanisms of biological mineralization and considered the effects of the bisphosphonates.Hydroxyethylidene-1, 1-bisphosphonate (HEBP) was administered to rats by subcutaneous injection of 10mg P/kg for seven weeks. The incisors of the rats were removed and the dentin matrix proteins were analyzed biochemically. The amount of matrix proteins was relatively increased in the incisors of the experimental rats, though mineralization of the incisors of the those rats was reduced compared with that of the control rats. Dentin phosphophoryns, unique phosphoproteins of dentin, were also elevated in the experimental rats. Nevertheless, the composition of other non-collagenous proteins of dentin was essentially unchanged by the treatment.Inhibition of mineralization by bisphosphonate may not be mediated by inhibition Of synthesis of noncollagenous matrix proteins, but mainly by inhibition of calcium phosphate deposition. Moreover, it is possible that the synthesis of phosphophoryns was promoted by the treatment.
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