Effects of deflazacort on aspects of bone formation in cultures of intact calvariae and osteoblast-enriched cells.
Deflazacort, a synthetic glucocorticoid reported to have bone-sparing properties in vivo, and cortisol were compared for their effects on bone formation in vitro. Deflazacort and cortisol were studied for their effects on DNA and collagen synthesis in cultures of intact fetal rat calvariae and of osteoblast-enriched (Ob) cells from 21- to 22-day-old fetal rat parietal bone. Both steroids were also examined for their effects on skeletal insulin-like growth factor (IGF) I production, which is decreased by cortisol and appears relevant to its mode of action. After 24 h of culture, deflazacort and cortisol had limited effects on the parameters studied, although cortisol at 100 nM decreased [3H]proline incorporation into collagen in intact calvariae. In contrast, after 72 h deflazacort and cortisol at 1-100 nM inhibited the incorporation of [3H]thymidine into DNA and at 100 nM decreased the incorporation of [3H]proline into collagen and noncollagen protein in intact calvariae. Deflazacort and cortisol at 10-1000 nM decreased calvarial collagen degradation to a similar extent. Both steroids had a similar activity, and at 100 nM for 72 h they decreased IGF-I production by calvariae; however, cortisol at 10 nM was somewhat more effective than deflazacort in decreasing IGF-I levels. Deflazacort and cortisol had analogous effects in Ob cell cultures. After 24 h of treatment, deflazacort at 100-1000 nM and cortisol at 10-1000 nM decreased the labeling of DNA, and both steroids at 100-1000 nM caused a similar decrease in [3H]proline incorporation into collagen in Ob cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Canalis
E
E
Department of Research, Saint Francis Hospital, Hartford, Connecticut.
Avioli
L
L
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011282:Pregnenediones / Q000494:pharmacology*; D011392:Proline / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats
D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D004247:DNA; D011392:Proline; C021988:deflazacort; D006854:Hydrocortisone