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

Abstract

Clones of embryonic chick chondrocytes were isolated and collagen biosynthesis followed as the clones grow and eventually lose division capacity. Analysis of collagen type at each successive subculture until the time of cellular senescence showed that a change in synthesis occurs from the cartilage-specific Type II collagen (chain composition [.alpha.1(II)]3) to mixture of Type I collagen (chain composition [.alpha.1(I)]2.alpha.2) and the Type I trimer (chain composition [.alpha.1(I)]3). The expression of the chick chondrocyte phenotype is unstable in vitro, and 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 were observed after growth of chondrocytes for a few days in 5-bromo-2''-deoxyuridine, growth in this analog accelerates those changes that eventually lead to cellular senescence.