Effect of steroid hormones on endotoxin-mediated cartilage degradation

Abstract

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.

Physiological levels of hydrocortisone maintain an optimal chondrocyte extracellular matrix metabolism

“…The decreased activity of the IL1 mediated catabolic pathways in hydrocortisone treated chondrocytes-as reported by others 46 -explains the well documented reduction of neutral protease activities in steroid treated osteoarthritic cartilage samples. 21 22 27 29 These studies, as well the results presented here, are in line with the observation that steroid hormones prevented the enzymatic degradation and depletion of ECM proteoglycan in a model of endotoxin mediated cartilage degradation 47 and retarded the degradation and clearance of sulphated proteoglycans from condylar cartilage of newborn mice treated with steroid hormone. 48 A functional IGF-1/IGFR1 pathway is critical for the synthesis of a normal ECM 31 and seems also to be essential for preservation of the components of this matrix.…”