Tetrapyrroles as inhibitors of normal cartilage metabolism: relative potency of different compounds.

Abstract

The present study was designed to explore the role of different tetrapyrroles as inhibitors of cartilage metabolism. We studied the effects of tetrapyrroles on the incorporation of [35S]sulfate into proteoglycans, [14C]-leucine into protein, and [3H]uridine into the RNA of normal cartilage from two different vertebrate classes using the embryonic chicken pelvic rudiment bioassay and the hypophysectomized rat costal cartilage bioassay, both very sensitive to cartilage growth factors and growth inhibitors. We compared the relative potencies of the following compounds: both metalloporphyrins (heme and chlorophyllin), linear tetrapyrroles (bilirubin), and heme proteins (hemoglobin, myoglobin, and cytochrome c). Hemoglobin and heme were the most potent inhibitors of rat cartilage metabolism, and bilirubin was a far more potent inhibitor of embryonic chick cartilage metabolism. Chlorophyllin had moderate inhibitory activity, especially on chick cartilage, whereas cytochrome c was inactive in these bioassays. Surprisingly, myoglobin was relatively ineffective despite its close similarity to heme and hemoglobin. The bilirubin-induced inhibition of sulfate incorporation into chick cartilage was partially prevented when glutathione was included in the incubation medium, suggesting that a free-radical mechanism may be involved. There were significant differences in the sensitivity of the two cartilages studied, indicating there may be species-dependent sensitivity to different tetrapyrroles.