Effects of 1-hydroxyethylidene-1,1 bisphosphonate and (chloro-4 phenyl) thiomethylene bisphosphonic acid (SR 41319) on the mononuclear cell factor-mediated release of neutral proteinases by articular chondrocytes and synovial cells.

Articular chondrocytes and synovial cells were stimulated to produce collagenase, neutral casein and proteoglycan-degrading proteinases by conditioned medium from human peripheral blood mononuclear cells. Collagenase, neutral casein and proteoglycan-degrading proteinase secretion was inhibited by SR 41319, a new bisphosphonate, in a concentration-dependent manner. Complete inhibition was achieved at about 0.3 mM. EHDP exhibited the same general profile but was about 10-fold less active and never completely inhibited the enzyme secretion. When added before MCF, SR 41319 had a protective effect against subsequent activation of the cells by MCF. SR 41319 also inhibited the increase of enzyme secretion by cells previously stimulated with MCF. The results suggest that the ability of SR 41319 to inhibit the MCF-mediated secretion of neutral enzymes involved in cartilage destruction could be valuable in the management of connective tissue damage in rheumatoid arthritis.