Chondrocyte growth inhibition induced by homogentisic acid and its partial prevention with ascorbic acid

Cartilage damage termed ochronotic arthritis is the major pathology occurring in adult patients with alcaptonuria. We have investigated the effects of homogentisic acid (HGA), the metabolite accumulating in patients with alcaptonuria, on the in vitro proliferation of rabbit and human articular chondrocytes and human fibroblasts. Growth of these chondrocytes in monolayer decreased proportionally to increasing concentrations of HGA (0.001 mM to 1.0 mM). Substantial growth inhibition and morphologic abnormalities of chondrocytes were produced by a concentration of HGA (0.05 mM) similar to that found in serum of patients with alcaptonuria. Human fibroblasts required higher concentrations of HGA for a comparable degree of growth inhibition. The addition of ascorbic acid (0.57 mM) reduced this growth inhibition and prevented the morphologic changes.