Impaired response of human osteosarcoma (MG-63) cells to human parathyroid hormone induced by sustained exposure to high glucose.
It is known that osteopenia is frequently associated with diabetes mellitus. Although its mechanism is not well understood, impaired bone formation due to an osteoblast deficit seems to be a major factor as reflected by a fall in serum levels of osteocalcin and by the findings of low bone formation with bone histomorphometry. In the present study, we studied the effect of high glucose conditions on osteoblast by examining the responsiveness of human osteosarcoma (MG-63) cells to human parathyroid hormone 1-34 [hPTH-(1-34)]. MG-63 cells were cultured either with 5.5 mM glucose (normal glucose), 55.0 mM glucose (high glucose) or 5.5 mM glucose plus 49.5 mM mannitol (high mannitol) condition for 7 days. Both an increase in cAMP levels and an immediate increase in [Ca2+]i, induced by hPTH(1-34), were significantly lower in high glucose-treated cells than in those treated with normal glucose or high mannitol. Basal cAMP levels in the cells after a 7-day culture in high glucose conditions were significantly higher than in those in the other two groups. We concluded that high glucose specifically impaired the response to hPTH(1-34). This impairment seemed to arise from an increase in intracellular cAMP levels, which is reported to induce downregulation of PTH receptors.
Yoshida
O
O
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
Inaba
M
M
Terada
M
M
Shioi
A
A
Nishizawa
Y
Y
Otani
S
S
Morii
H
H
D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects*; D012516:Osteosarcoma; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019379:Teriparatide; D013997:Time Factors; D014407:Tumor Cells, Cultured
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019379:Teriparatide; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium