Hubbard J R, Mattmueller D R, Steinberg J J, Poppas D P, Sledge C B
Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Mol Cell Biochem. 1988 Jan;79(1):31-7. doi: 10.1007/BF00229395.
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(-9) to 10(-5) M) or other glucocorticoid hormones (dexamethasone, prednisolone, cortisone). Inhibition required the continued presence of the steroid. Removal of hydrocortisone (3 x 10(-7) M) 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(-5) M, but testosterone and beta-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 beta-estradiol, partially blocked by aldosterone and largely prevented by hydrocortisone administration.
软骨降解是各类人类关节炎的一个特征性表现，尤其是类风湿性关节炎和骨关节炎。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聚糖分解的影响，在该模型系统中，通过从培养的牛鼻软骨盘中释放蛋白聚糖可轻松对分解进行量化。内毒素（细菌脂多糖）处理使软骨蛋白聚糖的消耗增加了2至3倍。氢化可的松（10⁻⁹至10⁻⁵ M）或其他糖皮质激素（地塞米松、泼尼松龙、可的松）以浓度依赖的方式抑制了这种增加。抑制作用需要类固醇的持续存在。在内毒素处理的培养物中培养4天后去除氢化可的松（3×10⁻⁷ M），会导致内毒素反应迅速恢复，以至于在第二个4天培养期内蛋白聚糖释放接近最大水平。其他C-21类固醇激素（孕酮、醛固酮）在10⁻⁵ M时也具有抑制作用，但睾酮和β-雌二醇对内毒素作用影响很小。平均分子量较小的蛋白聚糖产物（琼脂糖CL-2B色谱法）从内毒素处理的软骨中释放出来，这与核心蛋白裂解一致。裂解不受β-雌二醇影响，部分被醛固酮阻断，而通过给予氢化可的松则基本可以防止。
