TRANSFORMING GROWTH-FACTOR-BETA PREDOMINANTLY STIMULATES PHENOTYPICALLY CHANGED CHONDROCYTES IN OSTEOARTHRITIC HUMAN CARTILAGE

Objective, One of the most prominent alterations that characterizes os teoarthritic cartilage damage is a reduction of proteoglycan content, reflecting an imbalance between synthesis and release of proteoglycans . Both synthesis and release depend on the activity of cartilage cells . Chondrocytes in the upper layer of moderately osteoarthritic human k nee cartilage appear to be phenotypically altered, including diminishe d proteoglycan synthesis. Transforming growth factor-beta (TGF-beta) a s a multifunctional growth factor has differential effects believed to depend on the differentiation stage of the target cells. We tested th e effect of TGF-beta on phenotypically altered chondrocytes in osteoar thritic cartilage. Methods, Human articular cartilage was cultured 4 d ays with or without TGF-beta. Proteoglycan synthesis was determined by (SO42-)-S-35 incorporation (biochemically and by autoradiography) for the upper and deep layer separately. Results, Osteoarthritic cartilag e proved more sensitive to TGF-beta than normal cartilage, Proteoglyca n synthesis of osteoarthritic cartilage was stimulated significantly m ore by 5 ng/ml TGF-beta than normal cartilage. For normal cartilage th is increase was equally divided among the upper and deeper layer of th e explants. For osteoarthritic cartilage the increase in proteoglycan synthesis could largely be attributed to the upper layer. Autoradiogra phy revealed that the relative (SO42-)-S-35 incorporation in the cell clusters, present in the upper layer of osteoarthritic cartilage, was significantly increased upon the addition of TGF-beta. Conclusion, Ost eoarthritic cartilage is more sensitive to TGF-beta than normal cartil age because phenotypically changed chondrocytes in the damaged upper l ayer of osteoarthritic cartilage are more sensitive to TGF-beta than c hondrocytes in the more intact deep layer and are more sensitive than the chondrocytes of normal cartilage. TGF-beta appears to redifferenti ate the phenotypically altered chondrocytes in osteoarthritic cartilag e.