Mayne R, Vail M S, Mayne P M, Miller E J
Proc Natl Acad Sci U S A. 1976 May;73(5):1674-8. doi: 10.1073/pnas.73.5.1674.
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.
已分离出胚胎鸡软骨细胞克隆,并在克隆生长并最终失去分裂能力的过程中追踪了胶原蛋白的生物合成。对每次连续传代直至细胞衰老时的胶原类型进行分析表明,合成发生了变化,从软骨特异性的II型胶原(链组成[α1(II)]3)转变为I型胶原(链组成[α1(I)2α2])和I型三聚体(链组成[α1(I)]3)的混合物。结果明确表明,鸡软骨细胞表型在体外不稳定,并且先前软骨细胞大规模培养的实验不能用成纤维细胞过度生长来解释。由于在软骨细胞在5-溴-2'-脱氧尿苷中生长几天后观察到了类似的形态变化和胶原蛋白生物合成中的类似“转换”,因此提出在这种类似物中的生长加速了那些最终导致细胞衰老的变化。