Growth factor responsiveness of human articular chondrocytes in aging and development

Abstract

Objective. To examine growth factor responses of human articular chondrocytes in aging and development. We have previously established a growth factor response profile for adult human articular chondrocytes and shown that transforming growth factor β (TGFβ) is the most potent mitogen among a variety of factors tested. Methods. Chondrocytes were isolated from human articular cartilage obtained from donors ages 11–83 years and tested in primary culture for proliferative responses to serum and recombinant preparations of the major chondrocyte growth factors. Proliferation was measured by ³H‐thymidine incorporation and cell counting. Skeletal maturity of the young donors was determined by radiographic assessment of Risser's index. Results. Chondrocytes showed a continuous age‐related decline in the proliferative response to serum. Analysis of recombinant growth factors showed that with increasing donor age, there was a decrease in the levels of DNA synthesis in response to all factors tested. In chondrocytes from adult donors, there was no change in the relative potencies of the different growth factors. The decrease in the levels of DNA synthesis as measured by ³H‐thymidine incorporation corresponded to a reduced rate of in vitro cell replication with increasing donor age. In addition to the quantitative changes in the proliferative responses of chondrocytes with increasing age, there was a qualitative change in the pattern of growth factor responses during development. Cells from young donors (ages 10–20) responded better to platelet‐derived growth factor, AA chain homodimer (PDGF‐AA) than to TGFβ1, while the inverse pattern was seen in cells from adult donors. This decrease in the response to PDGF‐AA was significantly correlated with increasing skeletal maturity. Conclusion. Chondrocyte growth factor responsiveness shows qualitative changes during development, and after skeletal maturity, there is a profound decline in the levels of DNA synthesis and cell replication in response to the known chondrocyte growth factors.