Role of advanced glycation end products in adynamic bone disease in patients with diabetic nephropathy.
Adynamic bone disease and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy. To clarify the role of AGEs in adynamic bone disease, we investigated the effect of these substances on cultured human osteoblasts and parathyroid cells. After 72 hours of incubation with AGEs-bovine serum albumin (BSA) (1,000 microgram/mL), there was significant inhibition of the synthesis of type I collagen and osteocalcin in response to stimulation with 10(-10) to 10(-8) M of 1,25-dihydroxycholecalciferol. In a human osteoblastic cell line (MG 63), AGEs-BSA did not affect human osteocalcin promoter activity. In human parathyroid cells, a receptor for AGEs was detected by reverse-transcriptase polymerase chain reaction. Incubation with AGEs-BSA for 48 hours significantly inhibited parathyroid hormone secretion in response to a low calcium concentration of 0.81 mM (P < 0.01). In HEK-293 cells, expressing calcium-sensing receptors, the same AGE concentration caused a significant potentiation of the extracellular Ca(2+) induced-intracellular calcium concentration after 24 and 48 hours of incubation (P < 0.05 and P < 0.01). These data suggest that AGEs are involved in the pathogenesis of adynamic bone disease by inhibiting osteoblastic activity and by inhibiting parathyroid hormone secretion in response to hypocalcemia.
Yamamoto
T
T
Departments of Pediatrics and Molecular Medicine, Osaka University Graduate School of Medicine, Osaka. takehisa_yamamoto@maple.city.minoh.osaka.jp
Ozono
K
K
Miyauchi
A
A
Kasayama
S
S
Kojima
Y
Y
Shima
M
M
Okada
S
S
D002117:Calcitriol / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology* / Q000378:metabolism*; D024042:Collagen Type I / Q000096:biosynthesis; D003928:Diabetic Nephropathies / Q000150:complications* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000096:biosynthesis; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism
D024042:Collagen Type I; D017127:Glycation End Products, Advanced; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D002117:Calcitriol; D002118:Calcium