Induction of matrix metalloproteinase-8 in human fibroblasts by basic calcium phosphate and calcium pyrophosphate dihydrate crystals: Effect of phosphocitrate

Although matrix metalloproteinase-8 (MMP-8) was regarded as the exclusive p roduct of the neutrophils, recent studies have shown that it is also expres sed in articular chondrocytes, rheumatoid synovial fibroblasts and endothel ial cells. Our aim was to determine the expression of MMP-8 in human fibrob lasts (HF) by reverse transcription/polymerase chain reaction (RT/PCR), Nor thern and Western blotting methods and MMP-8 activity assay. We have shown the expression of MMP-8 in HF and its dose-dependent upregulation by basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPPD) crystals which are markers of severe joint degeneration in osteoarthritis. These ef fects require new protein synthesis and are reversed by phosphocitrate (PC) . The results also show that this fibroblast MMP-8 is distinct from the neu trophil MMP-8 and from the fibroblast MMP-1. These results indicate that MM P-8 may play a significant role in the pathogenic effects of the crystals i n osteoarthritis.