Kidney and Metabolic Bone Diseases Vol.19 No.1(1-3)

Theme Impaired metabolism of bone and calcium in diabetes mellitus
Title Role of AGEs in pathogenesis of adynamic bone diseases in diabetes mellitus
Publish Date 2006/01
Author Takehisa Yamamoto Department of Pediatrics, Minoh City Hospital
[ Summary ] In patients with diabetes mellitus (DM) and end stage renal failure (ERF) with complications of DM, adynamic bone disease was often reported on from the basis of bone biopsy investigations. Serum levels of advanced glycation end-products (AGEs) were reported to be elevated. In this review, we showed the effects of AGEs on primary human osteoblasts and parathyroid cells in culture. AGEs were made by incubating bovine serum albumin with glucose 6 phosphate for 8 weeks. AGEs-BSA (1,000 μg / ml) levels showed an inhibitory effect on human osteoblasts in terms of the production of procolagen c propeptides and osteocalcin, which were regarded as bone forming parameters. On the other hand, the same concentration of AGEs-BSA inhibited the increase of parathyroid hormone secretion from the cultured human parathyroid cells induced by low calcium medium concentrations. Also, AGEs-BSA increased time dependently in relation to intracellular calcium levels in HEK 293 cells, expressing wild type human calcium-sensing receptors. These data suggested the important role of AGEs in the pathogenesis of adynamic bone disease in DM and ERF patients with DM complications.
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