Differential effects of 1,25-dihydroxyvitamin D3-analogs on osteoblast-like cells and onin vitro bone resorption

Gert Jan C.M. van den Bemd, Huibert A.P. Pols, Jan C. Birkenhäger, Wendy M.C. Kleinekoort, Johannes P.T.M. van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Although numerous studies have shown potent antiproliferative and differentiation-inducing effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and its analogs on cells not directly related to bone metabolism, only few reports focussed on the effects of these analogs on bone. We compared the action of several recently developed analogs with that of 1,25-(OH)2D3 on human (MG-63) and rat (ROS 17/2.8) osteoblast-like cells and onin vitro bone resorption. In MG-63 cells the analogs EB1089 and KH1060 were about 166,000 and 14,000 times more potent than 1,25-(OH)2D3 in stimulating type I procollagen and 100 and 6,000 times more potent in stimulating osteocalcin production, respectively. Also in ROS 17/2.8 cells EB1089 and KH1060 were most potent in inducing osteocalcin synthesis. In vitro bone resorption was 2.3 and 17.5 times more potently stimulated by EB1089 and KH1060, respectively. In MG-63 cells, 1,25-(OH)2D3 and the analogs inhibited cell proliferation, whereas both 1,25-(OH)2D3 and the analogs stimulated the growth of ROS 17/2.8 cells. Differences in potency could neither be explained by affinity for the vitamin D receptor nor by a differential involvement of protein kinase C in the action of the analogs. Together, these data show that also in bone the analogs EB1089 and KH1060 are more potent than 1,25-(OH)2D3 but that the potency of the analogs compared to 1,25-(OH)2D3 is dependent on the biological response. On the basis of these observations it can be concluded that the reported reduced calcemic effectin vivo is not the result of a decreased responsiveness of bone to these analogs. Lastly, in view of eventual clinical application of 1,25-(OH)2D3-analogs, the observed stimulation ofin vitro bone resorption and growth of an osteosarcoma cell line warrantin vivo studies to further examine these effects.

Original languageEnglish
Pages (from-to)337-346
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number3-4
Publication statusPublished - Dec 1995


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