Transforming growth factor-beta predominantly stimulates phenotypically changed chondrocytes in osteoarthritic human cartilage.

OBJECTIVE One of the most prominent alterations that characterizes osteoarthritic 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 knee cartilage appear to be phenotypically altered, including diminished proteoglycan synthesis. Transforming growth factor-beta (TGF-beta) as a multifunctional growth factor has differential effects believed to depend on the differentiation stage of the target cells. We tested the effect of TGF-beta on phenotypically altered chondrocytes in osteoarthritic cartilage. METHODS Human articular cartilage was cultured 4 days with or without TGF-beta. Proteoglycan synthesis was determined by (35)SO4(2-) incorporation (biochemically and by autoradiography) for the upper and deep layer separately. RESULTS Osteoarthritic cartilage proved more sensitive to TGF-beta than normal cartilage. Proteoglycan synthesis of osteoarthritic cartilage was stimulated significantly more by 5 ng/ml TGF-beta than normal cartilage. For normal cartilage this increase was equally divided among the upper and deeper layer of the explants. For osteoarthritic cartilage the increase in proteoglycan synthesis could largely be attributed to the upper layer. Autoradiography revealed that the relative (35)SO4(2-) incorporation in the cell clusters, present in the upper layer of osteoarthritic cartilage, was significantly increased upon the addition of TGF-beta. CONCLUSION Osteoarthritic cartilage is more sensitive to TGF-beta than normal cartilage because phenotypically changed chondrocytes in the damaged upper layer of osteoarthritic cartilage are more sensitive to TGF-beta than chondrocytes in the more intact deep layer and are more sensitive than the chondrocytes of normal cartilage. TGF-beta appears to redifferentiate the phenotypically altered chondrocytes in osteoarthritic cartilage.