Guenther H L, Felix R, Fleisch H
Calcif Tissue Int. 1984 Mar;36(2):145-52. doi: 10.1007/BF02405310.
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)
地夫可特是一种新型合成糖皮质激素，是泼尼松龙的恶唑啉衍生物。在先前的研究中发现，根据所使用的测试模型，地夫可特在动物体内不仅显示出比泼尼松龙更强的抗炎效力，而且在人体中，与等量的其他糖皮质激素相比，对骨矿物质代谢的有害影响更小。在本研究中，我们比较了地夫可特与地塞米松对各种大鼠骨细胞群体和软骨细胞中胶原蛋白合成的影响。通过对1日龄大鼠颅骨进行连续的时间依赖性胶原酶处理制备了三种骨细胞群体。每个细胞群体在Percoll梯度（10 - 90%）上进一步纯化，得到三个群体，其中两个群体的碱性和酸性磷酸酶以及对甲状旁腺激素的反应不同。用地夫可特和地塞米松（10^(-11) - 10^(-5) M）对骨细胞群体进行3天处理后发现，两种糖皮质激素虽然浓度不同，但均抑制胶原蛋白合成。21 - 去乙酰地夫可特（5β,11β,16β）-11,21 - 二羟基 - 2'-甲基 - 5 - H - 孕甾 - 1 - 烯醇[17,16 - d]恶唑 - 3,20 - 二酮），即该类固醇的可能活性形式，在给药后在体内形成，产生了与其前体几乎相同的结果。最初观察到抑制作用的糖皮质激素浓度，地塞米松为10^(-9) M，地夫可特为10^(-7) M。仅在早期组织消化过程中从骨中分离的细胞中，胶原蛋白合成的抑制作用明显受损，而在广泛胶原酶处理过程中获得的细胞中则未受损。从3个月大兔子的关节软骨中分离并在原代培养中生长的软骨细胞对这两种类固醇均无反应。（摘要截短至250字）
