Effect of steroid hormones on endotoxin-mediated cartilage degradation.
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.
Hubbard
J R
JR
Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Mattmueller
D R
DR
Steinberg
J J
JJ
Poppas
D P
DP
Sledge
C B
CB
D000818:Animals; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D046508:Culture Techniques; D004731:Endotoxins / Q000633:toxicity*; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D012485:Salmonella typhi
D004731:Endotoxins; D005938:Glucocorticoids; D011509:Proteoglycans; D006854:Hydrocortisone