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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Abstract

Type 1 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 22 mM glucose, 22 mM mannitol, 300 μg/ml AGE2, or 300 μg/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 μg/ml AGE2 significantly inhibited the mineralization of MC3T3-E1 cells, and 22 mM glucose in combination with either 300 μg/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.

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Correspondence

T. Yamaguchi

Department of Internal Medicine 1

Shimane University Faculty of Medicine

89-1 Enya-cho

Izumo

693-8501 Shimane

Japan

Phone: +81/853/20 21 83

Fax: +81/853/23 86 50

Email: yamaguch@med.shimane-u.ac.jp