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Influence of high glucose on 1,25‐dihydroxyvitamin D 3 ‐induced effect on human osteoblast‐like MG‐63 cells
Author(s) -
Inaba Masaaki,
Terada Makoto,
Koyama Hidenori,
Yoshida Osamu,
Ishimura Eiji,
Kawagishi Takahiko,
Okuno Yasuhisa,
Nishizawa Yoshiki,
Morii Hirotoshi,
Otani Shuzo
Publication year - 1995
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650100709
Subject(s) - endocrinology , medicine , osteocalcin , osteoblast , mannitol , chemistry , vitamin d and neurology , l glucose , receptor , secretion , diabetes mellitus , biology , alkaline phosphatase , enzyme , in vitro , biochemistry , islet
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 D 3 (1,25[OH] 2 D 3 ), an active form of vitamin D 3 , 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) 2 D 3 ‐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) 2 D 3 ‐induced increase in OC mRNA abundance in MG‐63 cells, suggesting that the inhibition of the 1,25(OH) 2 D 3 ‐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) 2 D 3 receptors in MG‐63 cells, without any change in the dissociation constant for 1,25(OH) 2 D 3 ; 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) 2 D 3 by reducing 1,25(OH) 2 D 3 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. (