BMP-2 and CDMP-2: stimulation of chondrocyte production of proteoglycan

A hallmark of intervertebral disc degeneration is loss of proteoglycans. Cytokines may be used to stimulate proteoglycan production in the disc to reverse or prevent disc degeneration. The effects of bone morphogenetic protein 2 (BMP-2) and cartilage-derived morphogenetic protein 2 (CDMP-2) (singly and jointly) on proteoglycan synthesis by a chondrocytic cell line (MC615) were studied. MC615 cells were dosed with BMP-2, CDMP-2, or both, cultured for 6 days, and then assayed as follows: (1) The proteoglycan content of the medium and extracellular matrix were determined by dimethyl-methylene blue staining; (2) cell numbers were determined after 6 days of culture using the Hoechst dye DNA assay; (3) aggrecan mRNA was measured with the reverse transcription-polymerase chain reaction and Northern blotting assays. Both BMP-2 and CDMP-2 significantly enhanced proteoglycan production and aggrecan mRNA expression in a dose-dependent manner, although BMP-2 is more effective than CDMP-2 in increasing sulfated proteoglycan production. But BMP-2 and CDMP-2 have only a slight, nonsignificant effect on cell proliferation. There is no evidence of antagonism or synergy between the two growth factors in the aggrecan gene expression.