Differential modulation of growth and phenotypic expression of chondrocytes in sparse and confluent cultures by growth factors in cartilage

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Abstract
The growth‐promoting actions of cartilage extracts (CE) on rabbit cultured chondrocytes were studied to assess the role of locally acting growth factors in the generation and expansion of highly differentiated cells. In the present study, DNA synthesis and proteoglycan synthesis in the cultured chondrocytes were monitored by flow cytofluorometry and double‐isotope autoradiography by using [3H]thymidine and [35S]sulfate. We report here that actions of the same set of growth factors extracted from cartilage evokes differential cellular responses depending upon cell density. Growth factors in the optimal dose of CE (2 μg/ml) strongly supported proliferation of the cells in sparse culture, but they had little effect on cells in confluent culture. In contrast, the optimal dose of fibroblast growth factor (FGF, 100 ng/ml) or epidermal growth factor (EGF, 40 ng/ml) did not reveal such a cell density‐dependent effect on cellular proliferation. However, growth factors in CE induced proteoglycan synthesis selectively in nonproliferating and expressing cells in confluent culture.