Long-term effects of osteogenic protein-1 on biosynthesis and proliferation of human articular chondrocytes.

OBJECTIVE To study the long-term effects of OP-1 on the biosynthesis and proliferation of human articular chondrocytes. METHODS Chondrocytes were released from human cartilage from 10 organ donors of different ages and cultured in alginate. They were exposed to OP-1 (0-200 ng/ml) for 3 to 60 days. Proteoglycan (35S-sulfate) and collagen (3H-proline) synthesis were measured by radiolabeling. Proteoglycan content was determined by a dimethylmethylenblue assay, hydroxyproline content by a colorimetric assay, and DNA content by a fluorometric assay. RESULTS Long-term (60 days) cultures of human adult articular chondrocytes stimulated by OP-1 (50 ng/ml) revealed a relative decrease of proteoglycan and collagen synthesis. However, proteoglycan (5-fold) and collagen (1.4-fold) content were increased even after 60 days in culture when compared to controls. Maintaining the chondrocyte phenotype (aggrecan synthesis as the main proteoglycan) in long-term culture, OP-1 (50 ng/ml) stimulated proliferation up to 2.4-fold. CONCLUSION Maintaining a stable phenotype and accelerating matrix assembly and proliferation in long-term culture OP-1 might support the tissue engineering of human cartilage.