Comparative study of deflazacort, a new synthetic corticosteroid, and dexamethasone on the synthesis of collagen in different rat bone cell populations and rabbit articular chondrocytes

Abstract

Deflazacort is a new synthetic glucocorticoid which is an oxazoline derivative of prednisolone. In previous studies, it was shown that deflazacort, depending on the test model used, not only showed considerably more antiinflammatory potency than prednisolone in animals but also caused less deleterious effects on bone mineral metabolism than equivalent amounts of other glucocorticoids in man. In this study, we have compared the effects of deflazacort with those of dexamethasone on the synthesis of collagen in various rat bone cell populations and chondrocytes. Three bone cell populations were prepared by sequential time-dependent collagenase treatment of 1-day-old rat calvaria. Each cell population was further purified on a Percoll gradient (10-90%) yielding three populations of which two are different in alkaline and acid phosphatase and response to parathyroid hormone. A 3-day treatment of bone cell populations with deflazacort and dexamethasone (10(-11)-10(-5) M) revealed that both glucocorticoids, although at different concentrations, inhibited collagen synthesis. 21-desacetyl-deflazacort (5 beta, 11 beta, 16 beta)-11,21-dihydroxy-2'-methyl-5-H-pregna-1-enol [17,16-d]oxazole-3,20-dione), the presumably active form of the steroid, which is formed in vivo after administration, produced nearly identical results as its precursor. Glucocorticoid concentrations at which inhibition was initially observed were 10(-9) M and 10(-7) M for dexamethasone and deflazacort respectively. Inhibition of collagen synthesis was significantly impaired only in cells isolated from bone during early tissue digestion, and not in those obtained during extensive collagenase treatment. Chondrocytes isolated from articular cartilage of 3-month-old rabbits and grown in primary cultures did not respond to either steroid.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis and Treatment of Steroid Osteoporosis

“…Rodent bone cells grown in culture show inhibition of protein and collagen synthesis (Peck et al. 1967;Wong, 1979;Guenther et al, 1984), cell growth (Chen & Feldman, 1979) and RNA synthesis (Peck et al 1967;1969) when exposed to glucocorticoids. Human osteoblast cells show similar responses during long-term incubation with supraphysiological steroid concentrations, but low glucocorticoid levels and short incubation periods stimulate cell growth and collagen synthesis (Gallagher ef al., 1984).…”

Effects of Inhaled Corticosteroids on the Growth Plates of Infant Rats

“…Dexamethasone inhibited chondrocyte proliferation in cultured fetal rat metatarsals [27]. Some other in vitro studies also demonstrated that glucocorticoids negatively affect cartilage proliferation [28,29]. In this study, the often-preferred Ki-67 proliferation marker was used to detect the inhibitory effects of corticosteroids on proliferation.…”

Effect of the synthetic glucocorticoid, deflazacort, on body growth, pulsatile secretion of GH and thymolysis in the rat

“…At comparable dosages, DFZ was associated with less growth retardation than other corticosteroids in children with different diseases (27)(28)(29)(30) and in rats (31). Studies on comparable dosages show a ratio of 1:31-1:33 for DFZ to CORT in vivo in rats (31)(32)(33)(34)(35). These bioequivalence studies are based on carrageenin-and nystatin-induced edema, thymolytic effects, and the ex vivo binding to glucocorticoid receptors of various glucocorticoids.…”