Open AccessEffects of colchicine on collagenase in cultures of rheumatoid synovium
Author(s) -
Harris Edward D.,
Krane Stephen M.
Publication year - 1971
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780140602
Subject(s) - colchicine , collagenase , tissue culture , in vitro , hydroxyproline , enzyme , biochemistry , cell culture , explant culture , microbial collagenase , stimulation , mitosis , extracellular , chemistry , microbiology and biotechnology , biology , endocrinology , medicine , genetics
Rheumatoid synovium, cultured in vitro in media not enriched with serum, synthesized and released a specific collagenase. This enzyme appeared in measurable quantities only after three or more days of culture. Enzyme activity correlated well with hydroxyproline content in the culture media, indicating that extracellular matrix collagen in synovial explants was being degraded. Collagenase activity was found to be 2 to 10 times greater when colchicine (0.1 μg/ml) was added to the culture media. This stimulation of enzyme was dependent upon cells which could metabolize glucose and synthesize RNA; it was not dependent upon continued addition of colchicine to fresh culture media. Colchicine was found to depress 14 CO 2 production from glucose‐6‐ 14 C, whereas lactate formation and 14 CO 2 evolution from glucose‐1‐ 14 C were less markedly depressed. Mitotic figures were not seen in cells of tissue cultures in the absence of serum, nor was mitotic arrest observed in colchicine‐treated tissue. The effect of colchicine was not mediated by decreased degradation of the enzyme in culture nor by stimulation of release of stored enzyme, but was associated with an increase in radioactive leucine incorporation into several proteins synthesized by the cell, including collagenase.