Effect of steroid hormones on endotoxin-mediated cartilage degradation.
Effect of steroid hormones on endotoxin-mediated cartilage degradation.
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类固醇激素对内毒素介导的软骨降解的影响。
DOI：
10.1007/bf00229395
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发表时间：
1988
影响因子：
4.3
通讯作者：
Sledge,CB
中科院分区：
文献类型：
--
作者：
Hubbard,JR;Mattmueller,DR;Steinberg,JJ;Poppas,DP;Sledge,CB
软骨退化是各种类型人类关节炎的特征，尤其是类风湿性关节炎和骨性关节炎。在一个模型系统中研究了糖皮质激素和其他类固醇激素对软骨蛋白多糖分解的影响，在该模型系统中，蛋白多糖的分解很容易通过培养的牛鼻软骨盘中蛋白多糖的释放来量化。内毒素(细菌脂多糖)处理使软骨蛋白多糖的耗竭增加2-3倍。氢化可的松(10−9~10−5M)或其他糖皮质激素(地塞米松、强的松龙、可的松)以浓度依赖的方式抑制这种作用。抑制需要类固醇的持续存在。从内毒素处理的培养物中去除氢化可的松(3×10−7M)4天后，内毒素反应迅速恢复，蛋白多糖的释放在第二个培养4天达到最高水平。其他C-21类固醇激素(孕酮、醛固酮)在10−5M时也有抑制作用，但睾酮和β-雌二醇对内毒素作用影响不大。从内毒素处理的软骨中释放出平均摩尔质量较小的蛋白多糖产物(SepharoseCL-2B层析)，与核心蛋白裂解一致。卵裂不受β-雌二醇的影响，部分被醛固酮阻断，大部分被氢化可的松阻止。
Cartilage degradation is a characteristic feature of various types of human arthritis, notably rheumatoid arthritis and osteoarthritis. The influence of glucocorticoid and other steroid hormones on cartilage proteoglycan breakdown was examined in a model system in which breakdown is readily quantified by the release of proteoglycan from cultured bovine nasal cartilage discs. Endotoxin (bacterial lipopolysaccharides) treatment enhanced the depletion of cartilage proteoglycan by 2–3 fold. This was inhibited in a concentration-dependent manner by hydrocortisone (10−9to 10−5M) or other glucocorticoid hormones (dexamethasone, prednisolone, cortisone). Inhibition required the continued presence of the steroid. Removal of hydrocortisone (3 × 10−7M) after 4 days from endotoxin-treated cultures resulted in the rapid restoration of an endotoxin response, so that proteoglycan release approached maximum levels during a second 4-day culture period. Other C-21 steroid hormones (progesterone, aldosterone) were also inhibitory at 10−5M, but testosterone and β-estradiol showed little influence on endotoxin action. Proteoglycan products of smaller average mol wt (Sepharose CL-2B chromatography), consistent with core protein cleavages, were released from endotoxin-treated cartilage. Cleavage was unaffected by β-estradiol, partially blocked by aldosterone and largely prevented by hydrocortisone administration.