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Nerve growth factor (NGF) is probably made by many extraneural tissues and some mesenchymal tumors. The present study investigated the effects of NGF on the in vitro synthesis of macromolecules by embryonic chicken cartilage. Cartilage deoxyribonucleic acid and ribonucleic acid synthesis as estimated by radioactive thymidine and uridine incorporation were unaltered by NGF. Chondromucoprotein synthesis as determined by 35SO4 incorporation into cartilage proteins was significantly inhibited by as little as 2 mug/ml of NGF and markedly inhibited (65-82 percent) by 20 mug/ml. Total cartilage protein synthesis as indicated by the incorporation of radioactive leucine was slightly (14 percent) but significantly inhibited by NGF. Fractionation of cartilage proteins into collagen-rich and chondromucoprotein-rich fractions and further purification by polyacrylamide gel electrophoresis demonstrated that all of the inhibition of leucine incorporation was due to the inhibition of chondromucoprotein synthesis. Thus NGF causes a selective and unique inhibition of cartilage chondromucoprotein synthesis.

Chondrocytes grown in cell culture from micromelic chick sterna and 5-bromodeoxyuridine-treated normal cells showed reduced incorporation of sulfate into hyaluronidase-sensitive material as compared to normal chondrocytes. Proteochondroitin sulfate synthesized by normal embryonic chick chondrocytes in cell culture was heterogeneous on chromatography. The major chromatographic component was specifically inhibited in normal chondrocytes treated with 5-bromodeoxyuridine, and this component was absent in nanomelic chondrocytes.