Inflammatory bone resorption, a characteristic feature of periodontal
disease and rheumatoid arthritis, appears to be mediated by interleuki
n-1 beta (IL-1 beta). IL-1 beta has been shown to stimulate a wide ran
ge of proteolytic enzymes, including collagenases and plasminogen acti
vators, in particular chondrocytes, synovial cells, and isolated osteo
blasts. In this study, we have examined the hypothesis that IL-1 beta
may stimulate bone loss by inducing the activity of plasminogen activa
tors (PAs) in bone cultures. The latter would convert plasminogen to p
lasmin, which in turn can activate precursor procollagenase to collage
nase. Active collagenase would then break down the bone collagen matri
x. In the present study, release of Ca-45 from fetal rat long bones in
culture was studied in the presence of plasminogen and IL-1 beta. Pla
sminogen and IL-1 beta separately enhance resorption of fetal rat long
bones in vitro. When plasminogen and IL-1 beta are added together at
suboptimal levels, mainly additive effects are observed. The presence
of heat-inactivated serum does not alter these results. These data ten
d to indicate that IL-1 beta is stimulating bone resorption through bo
th PA-dependent and PA-independent pathways.