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

ABSTRACT

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.