Objective—To determine the effects of interleukin-
1β (IL-1β) and tumor necrosis factor-α (TNF-α) on
expression and regulation of several matrix-related
genes by equine articular chondrocytes.
Sample Population—Articular cartilage harvested
from grossly normal joints of 8 foals, 6 yearling horses,
and 8 adult horses.
Procedure—Chondrocytes maintained in suspension
cultures were treated with various doses of human
recombinant IL-1β or TNF-α. Northern blots of total
RNA from untreated and treated chondrocytes were
probed with equine complementary DNA (cDNA)
probes for cartilage matrix-related genes.
Incorporation of 35S-sulfate, fluorography of 14C-proline
labeled medium, zymography, and western blotting
were used to confirm effects on protein synthesis.
Results—IL-1β and TNF-α increased steady-state
amounts of mRNA of matrix metalloproteinases 1,
3, and 13 by up to 100-fold. Amount of mRNA of tissue
inhibitor of metalloproteinase-1 also increased
but to a lesser extent (1.5- to 2-fold). Amounts of
mRNA of type-II collagen and link protein were consistently
decreased in a dose-dependent manner.
Amount of aggrecan mRNA was decreased slightly;
amounts of biglycan and decorin mRNA were minimally
Conclusions and Clinical Relevance—Treatment of
cultured equine chondrocytes with IL-1β or TNF-α
resulted in marked alterations in expression of various
matrix and matrix-related genes consistent with the
implicated involvement of these genes in arthritis.
Expression of matrix metalloproteinases was
increased far more than expression of their putative
endogenous inhibitor. Results support the suggestion
that IL-1β and TNF-α play a role in the degradation of
articular cartilage in arthritis. (Am J Vet Res 2000;61: