Abstract:
:The effect of the physiological vitamin D metabolite 24R, 25-dihydroxyvitamin D3 [24R,25(OH)2D3] on human osteoblastic cells was assessed. Physiological concentrations (10(-9)-10(-8) M) of 24R, 25(OH)2D3 significantly increased the cyclic guanosine 5'-monophosphate (cGMP) content in the human osteoblastic cells by approximately 200% in 5 to 15 min. In contrast, 24S, 25-dihydroxyvitamin D3 had only a weak effect on the cGMP content, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] did not affect the content. The production of osteocalcin was not induced by 10(-9)-10(-8) M of 24R,25(OH)2D3 in the absence of 1,25(OH)2D3. However, the same concentration of 24R,25(OH)2D3 showed stimulatory effects on osteocalcin synthesis in the presence of 10(-9) M 1, 25(OH)2D3. Rp-8Br-cyclic GMP, a specific inhibitor of cyclic GMP-dependent protein kinase, significantly inhibited the cooperative effect of 24R,25(OH)2D3 with 1,25(OH)2D3 on the osteocalcin synthesis, although Rp-8Br-cyclic AMP, a specific inhibitor of cyclic AMP-dependent protein kinase, did not affect the cooperative effect. In addition, okadaic acid enhanced the osteocalcin synthesis induced by 1,25(OH)2D3. These observations suggest that 24R,25(OH)2D3 has a unique activity of increasing cGMP contents in osteoblastic cells, and that the increase in cGMP contents may lead to the cooperative effect of 24R,25(OH)2D3 with 1, 25(OH)2D3 on osteocalcin synthesis. These data support the hypothesis that 24R,25(OH)2D3 has a physiological role in human bone and mineral metabolism.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Yamamoto T,Ozono K,Shima M,Yamaoka K,Okada Sdoi
10.1006/excr.1998.4189subject
Has Abstractpub_date
1998-10-10 00:00:00pages
71-6issue
1eissn
0014-4827issn
1090-2422pii
S0014-4827(98)94189-1journal_volume
244pub_type
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