Cultured rabbit joint chondrocytes were exposed to
diacerhein (DAR : ART 50, Negma, 10(-6) to 10(-4) M), which has proved effective and safe when given for two months for the treatment of
osteoarthritis. Experiments were performed with and without 500 pg/ml human recombinant
interleukin-1 to determine whether
diacerhein antagonizes the effects of this monokine.
Glycosaminoglycan production was measured by 35S-sulfate incorporation followed by
cetylpyridinium precipitation,
collagen production by 3H-proline labeling and bacterial
collagenase digestion, and
collagenase production by determination of the amount of 3H-collagen that underwent degradation. Incubation of chondrocytes with
diacerhein for 24 hours was not associated with substantial changes in
glycosaminoglycan or
collagen production but substantially antagonized interleukin-1-mediated enhancement of
collagenase production. With longer incubation periods (6 days) with the 10(-6) M concentration of
diacerhein, production of
glycosaminoglycans and
collagen increased. Incubation with both
diacerhein and
interleukin-1 for six days partly antagonized the
cytokine's inhibitory effect on
glycosaminoglycan and
collagen production. During these experiments, the medium's ability to break down
collagen was consistently reduced by
diacerhein, even in the presence of
interleukin-1. These data demonstrate that
diacerhein can reduce or even abolish interleukin-1-mediated enhancement of
collagenase production by joint chondrocytes. This effect may lead to less erosion of cartilage in degenerative
joint diseases.