Effect of protocatechualdehyde,a metabolite of the novel antirheumatic agent ACP,on chondrocyte metabolism

We investigated PAL (protocatechualdehyde), one of the metabolites of ACP (3,4-diacetoxy benzylidene diacetate) which is a candidate novel antirheumatic agent. Specifically, we studied the effect and mechanism of action of PAL on chondrocyte metabolism using a primary culture of chondrocytes from rabbit articular cartilage. Proteoglycan (PG) depletion in the chondrocyte matrix was induced by the addition of human recombinant interleukin-1α (hrlL-1α) or phorbol myristate acetate (PMA). PAL (10–100 μM) significantly reduced the induced PG depletion and [³⁵S]-PG release in the chondrocyte matrix. The matrix metalloproteinase (MMPs) inhibitor, 1,10-phenanthroline, and protein kinase C (PKC) inhibitor, H-7, also blocked PG depletion and [³⁵S]-PG release. Furthermore, H-7 reduced the production of MMPs induced by hrlL-1α in the culture media of chondrocytes. These results indicate that hrlL-1α causes MMPs production by the activation of PKC, which is followed by [³⁵S]-PG release in the chondrocyte matrix. While PAL also resulted in significant inhibition of MMPs production, which might be mediated by PKC activation, it had no direct influence on PKC activity. These results suggest that PAL affects chondrocyte metabolism by the inhibition of MMPs production. ©1993 Wiley-Liss, Inc.