Potential predictive markers for proliferative capacity of cultured human articular chondrocytes: PCNA and p21

The purpose of this study was to investigate age-related changes in the proliferative ability of human articular chondrocytes in culture. In addition, the possible markers for the proliferative capacity of chondrocytes were examined. Chondrocytes obtained from human articular cartilages of young (under 40 years) or old (over 60 years) individuals were expanded until their growth was arrested. The number of cells and the type II collagen phenotype were determined together with the expression levels of proliferating cell nuclear antigen (PCNA) and p21(WAF1/CIP) along with the passages of cultured chondrocytes. The results showed that young chondrocytes had higher proliferative capacity and viability than old chondrocytes. The growth arrest and the cessation in the expression of type II collagen were accompanied by down-regulation of PCNA and up-regulation of p21(WAF1/CIP) levels in both young and old chondrocytes. Notably, the expression levels of PCNA and p21(WAF1/CIP) along with the passages were correlated inversely to each other and showed distinct patterns between young and old chondrocytes. These results suggest that senescence of human articular chondrocytes leads to the decrease in the proliferative capacity and phenotypic stability. In addition, PCNA and p21 could be molecular markers that represent the status of these age-related properties of human articular chondrocytes in vitro.