ARTICULAR CHONDROCYTES PRODUCE FACTORS THAT INHIBIT MATURATION OF STERNAL CHONDROCYTES IN SERUM-FREE AGAROSE CULTURES - A TGF-BETA INDEPENDENT PROCESS

Under normal conditions, articular chondrocytes persist throughout pos tnatal life, whereas ''transient'' chondrocytes, which constitute the bulk of prenatal and early postnatal cartilaginous skeleton, undergo m aturation, hypertrophy, and replacement by bone cells. The mechanisms regulating the markedly different behavior and fate of articular and t ransient chondrocytes are largely unclear. In the present study, we as ked whether articular chondrocytes possess dominant antimaturation pro perties which may subtend their ability to persist throughout life. Ad ult chicken articular chondrocytes and transient maturing chondrocytes from the core region of day 17 chick embryo cephalic sternum were cul tured or cocultured in serum-free agarose conditions. When the sternal cells were grown by themselves, they quickly developed into hypertrop hic type X collagen-synthesizing cells; however, when they were cocult ured with as few as 10% articular chondrocytes or fed with articular c hondrocyte-conditioned medium, their maturation was markedly impaired, as revealed by a sharp drop in type X collagen synthesis. A similar, albeit less potent, antimaturation activity characterized resting and proliferating immature chondrocytes isolated from other regions of emb ryonic sternum. Transforming growth factor-beta 2 (TGF-beta 2) was pre viously suggested to be an inhibitor of chondrocyte maturation. We fou nd, however, that treatment with a neutralizing antiserum to TGF-beta did not counteract the inhibition of maturation in cocultures of artic ular and maturing core sternal chondrocytes. Indeed, articular chondro cytes produced and accumulated relatively low levels of TGF-beta in th eir culture medium, about 15 ng/ml/48 h, of which over 90% was latent; surprisingly, maturing sternal core chondrocytes accumulated over 10- fold more TGF-beta in the medium, about 150 ng/ml/48 h, of which over 20% was endogenously active. These results indicate that articular cho ndrocytes do possess dominant antimaturation properties which appear t o be TGF-beta independent. The TGF-beta s may thus have a more promine nt role in the terminal phases of chondrocyte maturation, as indicated by their abundance and greater activity in hypertrophic chondrocytes.