A COMPARISON OF THE EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA-1 ON PYROPHOSPHATE ELABORATION FROM VARIOUS ARTICULAR TISSUES

Objective. The purpose of this study was to determine the effect of transforming growth factor beta1 (TGFbeta1) on inorganic pyrophosphate (PPi) elaboration from articular tissues to better understand the pathophysiology of calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joint. Methods. PPi was measured in the media of adult porcine articular tissue in organ culture and monolayer cultures. Results. TGFbeta1 strongly stimulated PPi elaboration by porcine fibrocartilage and hyaline cartilage. It modestly increased PPi elaboration by ligament, and had no effect on PPi elaborated by synovium. Of all cell types tested in cell culture, only chondrocytes responded to TGFbeta1 by significantly increasing PPi elaboration. Conclusion. TGFbeta1 stimulates PPi elaboration from hyaline cartilage, fibrocartilage, and ligament, indicating that there is in situ CPPD crystal formation in these tissues. The ability of tissues to respond to TGFbeta1 by increasing PPi elaboration correlates with the prevalence of CPPD crystal deposition found clinically. The unique response of chondrocyte monolayers to TGFbeta1 reinforces the key role of the chondrocyte in PPi elaboration in the joint. These findings support an etiologic role for responsiveness to TGFbeta1 in CPPD disease.