Ascorbic Acid Stimulates the Resorption of Canine Articular Cartilage Induced by a Factor Derived from Activated Rabbit Macrophages

Articular cartilage explants from the knees of mongrel dogs release 5–10% of their proteoglycan content spontaneously when cultured for 4 days in serum-free modified Bigger's medium. A factor synthesized and secreted by lipopolysaccharide-stimulated rabbit macrophages can stimulate this release of proteoglycan by 2 to 3-fold. The release of proteoglycan in response to macrophage factor is maximal in the presence of 1.5–50 μg/ml l-ascorbic acid. In the absence of ascorbate, or with high levels of ascorbate (150 μg/ml), the effect of the factor is diminished by 50%. d-isoascorbate, reduced glutathione, or dithiothreitol cannot substitute for l-ascorbate in producing this effect, while dehydroascorbate can.