24- and 26-homo-1,25-dihydroxyvitamin D3 analogs: potencies on in vitro bone resorption differ from those reported for cell differentiation.
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.
Paulson
S K
SK
Department of Pediatrics, Northwestern University Medical School, Chicago, IL 60611.
Perlman
K
K
DeLuca
H F
HF
Stern
P H
PH
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects / Q000196:embryology; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D046508:Culture Techniques; D051381:Rats; D011919:Rats, Inbred Strains
C052404:26-homo-1,25-dihydroxyvitamin D3; C052403:24-homo-1,25-dihydroxyvitamin D3; D002117:Calcitriol