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 pr oliferation of human articular chondrocytes. Methods Chondrocytes were released from human cartilage from 10 organ donor s of different ages and cultured in alginate. They were exposed to OP-1 (0- 200 ng/ml) for 3 to 60 days. Proteoglycan (S-35-sulfate) and collagen (H-3- proline) synthesis were measured by radiolabeling. Proteoglycan content was determined by a dimethylmethylenblue assay, hydroxyproline content by a co lorimetric 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-fo ld) content were increased even after 60 days in culture when compared to c ontrols. Maintaining the chondrocyte phenotype (aggrecan synthesis as the m ain proteoglycan) in long-term culture, OP-1 (50 ng/ml) stimulated prolifer ation 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 engine ering of human cartilage.