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Effect of steroid hormones on endotoxin-mediated cartilage degradation

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Summary

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 10−5M) 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.

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Authors and Affiliations

  1. The Orthopedic Research Laboratory, Departments of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, 02115, Boston, MA, USA

    John R. Hubbard, Danette R. Mattmueller, Dix P. Poppas & Clement B. Sledge

  2. The Orthopedic Research Laboratory, Departments of Biochemistry, Brigham and Women's Hospital, Harvard Medical School, 02115, Boston, MA, USA

    John R. Hubbard

  3. The Orthopedic Research Laboratory, Departments of Medicine, Brigham and Women's Hospital, Harvard Medical School, 02115, Boston, MA, USA

    James J. Steinberg

Authors
  1. John R. Hubbard
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  2. Danette R. Mattmueller
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  3. James J. Steinberg
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  4. Dix P. Poppas
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  5. Clement B. Sledge
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Hubbard, J.R., Mattmueller, D.R., Steinberg, J.J. et al. Effect of steroid hormones on endotoxin-mediated cartilage degradation. Mol Cell Biochem 79, 31–37 (1988). https://doi.org/10.1007/BF00229395

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  • DOI: https://doi.org/10.1007/BF00229395

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