Avocado/soya unsaponifiables enhance the expression of transforming growthfactor beta 1 and beta 2 in cultured articular chondrocytes

Objective. Avocado and soya unsaponifiables (ASU) have been reported to exe rt beneficial effects in the treatment of periodontal and osteoarticular di seases. They are supposed to stimulate deposition and repair of extracellul ar matrix components, but the mechanisms underlying their action are not we ll understood. In view of the repair potential of osteoarthritic (OA) carti lage and the role that the transforming growth factor beta (TGF beta) syste m could play in that process, we carried out in vitro studies to determine the mechanism of action of ASU on articular chondrocytes that may account f or the beneficial effects on cartilage metabolism. Methods. Cultured bovine articular chondrocytes were treated with various c oncentrations of ASU, and the expression of both TGF beta isoforms, 1 and 2 , and their receptors (TGF beta RI and TGF beta RII) was determined by Nort hern blot and reverse transcriptase-polymerase chain reaction. Cell transfe ction with TGF beta 1 promoter constructs nas also used to delineate the ci s-acting sequences mediating ASU responsiveness in chondrocytes. The level of plasminogen activator inhibitor 1 (PAI-1) mas also evaluated ba Northern blotting and protein radiolabeling. Results. The data indicated that ASU stimulate the expression of TGF beta 1 TGF beta 2, and PAI-1 bg articular chondrocytes. In contrast? the levels o f TGF beta RI and TGF beta RII were not significantly affected by the compo und, Treatment of bovine articular chondrocytes transiently transfected wit h TGF beta 1 promoter constructs suggested that the effect on TGF beta 1 ex pression is mediated by the region located between -732 and -1132 bp, Conclusion. The results indicate that the ASU-induced stimulation of matrix synthesis previously reported in cultured articular chondrocytes could be explained qv the ability to enhance TGF beta expression in these cells. Fur ther, ASU increase the production of PAI-1, an effect that could help in bl ocking the plasmin cascade that leads to metalloprotease activation. These data suggest that the compound has properties that might promote TGF beta-i nduced matrix repair mechanisms in articular cartilage.