24- and 26-homo-1,25-dihydroxyvitamin D3 analogs: potencies on in vitro bone resorption differ from those reported for cell differentiation.

Abstract

It has been proposed that the stimulatory effects of 1,25-dihydroxyvitamin D on bone resorption may be mediated through actions on differentiation of marrow cells into monocytic osteoclast precursors. In human promyelocytic leukemia cells (HL-60), 24- and 26-homo-1,25-dihydroxyvitamin D3 and their delta 22 analogs and 24,24-dihomo-1,25-dihydroxyvitamin D3 are 10-fold more potent than 1,25-dihydroxyvitamin D3, and delta 22-24,24,24-trihomo-1,25-dihydroxyvitamin D3 is equipotent with 1,25-dihydroxyvitamin D3 in inducing differentiation into the monocytic phenotype. The effect of these 1,25-dihydroxyvitamin D3 analogous on resorption of fetal rat limb bones in vitro was determined in the present study. 1,25-Dihydroxyvitamin D3 was equipotent with 24-homo-1,25-dihydroxyvitamin D3, delta 22-24-homo-1,25-dihydroxyvitamin D3, 26-homo-1,25-dihydroxyvitamin D3, and delta 22-26-homo-1,25-dihydroxyvitamin D3 for in vitro bone resorption, whereas 24,24-dihomo-1,25-dihydroxyvitamin D3 and delta 22-24,24,24-trihomo-1,25-dihydroxyvitamin D3 were inactive. The failure of these analogs to show a higher bone-resorbing activity than 1,25-dihydroxyvitamin D3 were inactive. The failure of these analogs to show a higher bone-resorbing activity than 1,25-dihydroxyvitamin D3 provides evidence to suggest that the mechanism of 1,25-dihydroxyvitamin D3-induced bone resorption may not involve stimulation of monocytic cell differentiation.

• Authors: S K Paulson, K Perlman, H F DeLuca, P H Stern
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 5 Issue 2 Pg. 201-6 (Feb 1990) ISSN: 0884-0431 [Print] United States
• PMID: 2316407 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 26-homo-1,25-dihydroxyvitamin D3
• 24-homo-1,25-dihydroxyvitamin D3
• Calcitriol

Topics

• Animals
• Bone Resorption (chemically induced)
• Bone and Bones (drug effects, embryology)
• Calcitriol (analogs & derivatives, pharmacology)
• Cell Differentiation (drug effects)
• Culture Techniques
• Rats
• Rats, Inbred Strains