Abstract. In bone forming cartilage in vivo, cells undergo terminal differentiation, whereas most of the cells in normal articular cartilage do not . Chondrocyte hypertrophy can be induced also in vitro by diffusible signals. We have identified growth factors or hormones acting individually on 17-d chick embryo sternal chondrocytes cultured in agarose gels under strictly serumfree conditions. Insulin-like growth factor I or insulin triggered the first steps of chondrocyte maturation, i.e., cell proliferation and increased matrix deposition while the chondrocytic phenotype was maintained. However, cells did not progress to the hypertrophic stage. Proliferation and stimulated collagen production was preceded by a lag period, indicating that synthesis C ARTILAGE cells in situ modulate their phenotype in response to environmental stimuli . Pluripotent mesenchYmal cells differentiate into resting chondrocYtes characterized by a moderate rate of synthesis of aggregating proteoglycans and collagens 11, IX, and XI. Most of the cells maintain this phenotype in joints where cartilage is permanent . During endochondral ossification in development, growth, and repair of bones, however, resting chondrocytes differentiate further. Initially, they proliferate and, later, they become hypertrophic in that they drastically increase both their volume and metabolic activity. Hypertrphic cells deposit large quantities ofextracellular matrix containing cartilage-specific proteoglycans and collagens including collagen X, a marker for this stage ofdifferentiation (Schmid and Linsenmayer, 1985). In contrast to resting and proliferative cartilage cells, hypertrophic cells also produce alkaline phosphatase .The phenotypic flexibility ofchondrocytes is also apparent in vitro . In monolayer culture, the cells can gradually lose the cartilage phenotype and begin to resemble mesenchymal cells (Holtzer et al ., 1960) and they produce macromolecules not normally found in cartilage (Mayne et al ., 1976;von der Mark et al ., 1977) . By contrast, in suspension culture stabilized by semisolid gels (Horwitz and Dorfman, 1970), chondrocytes remain differentiated and cells modulated in monolayer culture reexpress the cartilage phenotype C The Rockefeller University Press,
