Changes in type of collagen synthesized as clones of chick chondrocytes grow and eventually lose division capacity.

Clones of embryonic chick chondrocytes have been isolated and collagen biosynthesis has been followed as the clones grow and eventually lose division capacity. Analysis of collagen type at each successive subculture until the time of cellular senescence has shown that a change in synthesis occurs from the cartilage-specific Type II collagen (chain composition [alpha1(II)]3) to a mixture of Type I collagen (chain composition [alpha1(I)2alpha2) and the Type I trimer (chain composition[alpha1(I)]3). The results demonstrate unequivocally that the expression of the chick chondrocyte phenotype is unstable in vitro, and that previous experiments with mass cultures of chondrocytes cannot be accounted for by overgrowth of fibroblasts. Since similar morphological changes and a similar "switching" in collagen biosynthesis have been observed after growth of chondrocytes for a few days in 5-bromo-2'-deoxyuridine, it is proposed that growth in this analog accelerates those changes that eventually lead to cellular senescence.