The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs
The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs
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DOI：
10.1055/s-2007-991157
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发表时间：
2007-12-01
影响因子：
2.2
通讯作者：
Sugimoto, T.
中科院分区：
文献类型：
--
作者：
Ogawa, N.;Yamaguchi, T.;Sugimoto, T.
已知I型糖尿病与骨量减少和骨折增加相关。这被认为是由于成骨细胞骨形成的减少而不是骨吸收的增加，但确切的机制尚不清楚。在这项研究中，我们研究了在糖尿病发病机制和并发症中起关键作用的高糖或晚期糖基化终产物（AGEs）是否影响成骨细胞MC 3 T3-E1细胞的分化。首先，将MC 3 T3-E1细胞在含有22 mM葡萄糖、22 mM甘露醇、300 μ g/ml AGE 2或300 μ g/ml AGE 3的培养基中孵育。通过von Kossa染色和茜素红染色，这些试剂中的每一种单独都不影响细胞的矿化。实时荧光定量PCR结果显示，高糖可显著增加AGEs受体mRNA的表达，而甘露醇和AGEs则无此作用。接下来，我们研究了高糖和AGEs对MC 3 T3-E1细胞分化的联合作用。22 mM葡萄糖和300 μ g/ml AGE 2的组合显著抑制MC 3 T3-E1细胞的矿化，并且22 mM葡萄糖与300 μ g/ml AGE 2或AGE 3的组合明显降低骨钙素mRNA表达。这些结果表明，高葡萄糖或AGEs单独可能对成骨细胞分化没有影响，但它们的组合可以通过葡萄糖诱导的β-淀粉样蛋白表达增加来额外或协同抑制成骨细胞矿化。
Type I diabetes mellitus is known to be associated with reduced bone mass and increased bone fractures. This is thought to be due to a decrease in osteoblastic bone formation rather than an increase in osteoclastic bone resorption, but the precise mechanism is unknown. In this study, we examined whether or not high glucose or advanced glycation end-products (AGEs), which play key roles in the pathogenesis and complications of diabetes, affect the differentiation of osteoblastic MC3T3-E1 cells. First, MC3T3-E1 cells were incubated in media containing either 22mM glucose, 22mM mannitol, 300 mu g/ml AGE2, or 300 mu g/ml AGE3. Each of these agents alone did not affect the mineralization of the cells by von Kossa staining and Alizarin red staining. However, high glucose but not mannitol or AGEs markedly increased mRNA expression of AGE receptor (RAGE) by real-time PCR. Next, we examined the combined effects of high glucose and AGEs on the differentiation of MC3T3-E1 cells. The combination of 22 mM glucose and 300 mu g/ml AGE2 significantly inhibited the mineralization of MC3T3-E1 cells, and 22mM glucose in combination with either 300 mu g/ml AGE2 or AGE3 apparently decreased osteocalcin mRNA expression. These results suggest that high glucose or AGEs alone might have no effect on osteoblastic differentiation, but their combination could additionally or synergistically inhibit osteoblastic mineralization through glucose-induced increase in RAGE expression.