Effects of vitamin D3 on signaling by prostaglandin E2 in osteoblast-like cells

✍ Scribed by Haruhiko Tokuda; Jun Kotoyori; Atsushi Suzuki; Yutaka Oiso; Osamu Kozawa

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 602 KB
• Volume: 52
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240520213

✦ Synopsis

We investigated the effects of vitamin D3 on the signaling pathways by prostaglandin E, (PGE2) in osteoblast-like MC3T3-El cells. The pretreatment with 1,25-dihydroxyvitamin D3 (1 ,25-(OH),D3), an active form of vitamin D3, significantly inhibited cAMP accumulation induced by 10 (LM PGE, in a dose-dependent manner in the range between 1 pM and 1 nM. This effect of 1,25-(OH)*D3 was dependent on the time of pretreatment up to 8 h.

1 ,25-(0H)*D3 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),D3 significantly inhibited PGE,-induced IP3 formation in a dose-dependent manner between 10 pM and 1 nM. However, 1,25-(OH),D3 had little effect on NaF-induced IP, formation. The pretreatment with 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, affected neither cAMP accumulation nor IP3 formation induced by PGE,. These results strongly suggest that 1,25-(OH),D3 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 PGE, receptor and GTP-binding protein, probably C,,.