Effects of vitamin D3 on signaling by prostaglandin E2 in osteoblast-like cells.
We investigated the effects of vitamin D3 on the signaling pathways by prostaglandin E2 (PGE2) in osteoblast-like MC3T3-E1 cells. The pretreatment with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, significantly inhibited cAMP accumulation induced by 10 microM PGE2 in a dose-dependent manner in the range between 1 pM and 1 nM. This effect of 1,25-(OH)2D3 was dependent on the time of pretreatment up to 8h. 1,25-(OH)2D3 also inhibited the cAMP accumulation induced by NaF, a GTP-binding protein activator, or forskolin which directly activates adenylate cyclase. On the other hand, 1,25-(OH)2D3 significantly inhibited PGE2-induced IP3 formation in a dose-dependent manner between 10 pM and 1 nM. However, 1,25-(OH)2D3 had little effect on NaF-induced IP3 formation. The pretreatment with 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, affected neither cAMP accumulation nor IP3 formation induced by PGE2. These results strongly suggest that 1,25-(OH)2D3 modulates the signaling by PGE2 in osteoblast-like cells as follows: the inhibitory effect on the cAMP production is exerted at a point downstream from adenylate cyclase and the inhibitory effect on the phosphoinositide hydrolysis is exerted at the point between the PGE2 receptor and GTP-binding protein, probably Gi2.
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
H
H
Tokuda
J
J
Kotoyori
A
A
Suzuki
Y
Y
Oiso
O
O
Kozawa
D000818:Animals; D002460:Cell Line; D002762:Cholecalciferol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology
D010716:Phosphatidylinositols; D002762:Cholecalciferol; D005576:Colforsin; D012969:Sodium Fluoride; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D015232:Dinoprostone