Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells
- 1 July 1995
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Bone and Mineral Research
- Vol. 10 (7), 1050-1056
- https://doi.org/10.1002/jbmr.5650100709
Abstract
Impaired bone formation due to defective osteoblast function, as reflected in a decreased serum osteocalcin (OC) concentration in the patients with diabetes, has been implicated in the development of diabetic osteopenia. The role of hyperglycemia in this decrease in serum OC concentration was investigated. 1,25‐dihydroxyvitamin D3 (1,25[OH]2D3), an active form of vitamin D3, stimulated OC secretion from the human osteosarcoma cell line MG‐63 in a dose‐dependent manner. Exposure of the cells to high concentrations of glucose for 7 days significantly impaired 1,25(OH)2D3‐induced OC secretion as compared with that observed with cells maintained under normal glucose (5.5 mM) or high mannitol conditions. The inhibitory effect of glucose was in a dose‐dependent manner up to 55 mM. High glucose (55 mM) also attenuated the 1,25(OH)2D3‐induced increase in OC mRNA abundance in MG‐63 cells, suggesting that the inhibition of the 1,25(OH)2D3‐induced increase in OC secretion by exposure to a high concentration of glucose was, at least in part, mediated at the transcriptional level. High glucose significantly decreased the number of 1,25(OH)2D3 receptors in MG‐63 cells, without any change in the dissociation constant for 1,25(OH)2D3; this effect was not mimicked by high mannitol, indicating specificity for glucose. These observations suggest that a high glucose concentration significantly impairs the ability of osteoblastic cells to synthesize OC in response to 1,25(OH)2D3 by reducing 1,25(OH)2D3 receptor number, and that impaired cell function caused by sustained exposure to high glucose contributes to the defect in bone formation observed in the patients with diabetic osteopenia. (Keywords
This publication has 37 references indexed in Scilit:
- Effects of high concentrations of glucose on PTH secretion in parathyroid cellsKidney International, 1990
- Stabilization of 1,25-dihydroxyvitamin D-3 receptor in the human leukemia cell line, HL-60, with diisopropylfluorophosphateBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1989
- Vitamin D metabolites regulate osteocalcin synthesis and proliferation of human bone cells in vitroJournal of Endocrinology, 1985
- Vitamin D: Metabolism and Biological ActionsAnnual Review of Nutrition, 1984
- VITAMIN D: RECENT ADVANCESAnnual Review of Biochemistry, 1983
- Examination of Prevalence Rates of Possible Risk Factors in a Population with a Fracture of the Proximal FemurClinical Orthopaedics and Related Research, 1980
- Bone loss in diabetes: Effects of metabolic stateDiabetologia, 1979
- THE HYPERCALCIURIA OF DIABETES MELLITUS: ITS AMELIORATION WITH INSULINClinical Endocrinology, 1978
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976
- Equilibrium binding of estradiol by uterine cell suspensions and whole uteri in vitroBiochemistry, 1974