OSTEOINDUCTIVE ABILITY OF CONFLUENT SAOS-2 CELLS CORRELATES WITH ENHANCED EXPRESSION OF BONE MORPHOGENETIC PROTEINS

Implants of defatted, freeze-dried Saos-2 human osteosarcoma cells gro wn to confluency induce de novo bone formation in athymic mice. These cells are also richly endowed with bone morphogenetic proteins and exp ress mRNA for bone morphogenetic proteins 1, 2, 3, 4, and 6, as well a s for transforming growth factor-beta 1. Our aim was to study whether the ability to induce bone formation is related to the level of expres sion of bone morphogenetic protein. We studied the osteoinductive abil ities and levels of expression of bone morphogenetic protein of Saos-2 cells both during the growth phase and after confluency was reached. Subconfluent cells were at least 70% less effective in their osteoindu ctive ability than confluent cells. Comparison of bone morphogenetic p rotein mRNA expression in confluent and subconfluent cells revealed th at the latter had lower expression of all the mRNAs studied. The expre ssion of bone morphogenetic protein-1. bone morphogenetic protein-2, a nd bone morphogenetic protein-6 mRNAs was 2, 3, and 6 to 10-fold lower , respectively, in subconfluent cells. These results suggest that the ability of Saos-2 cells to induce de novo bone formation may be correl ated with the relative expression of these proteins; the expression of bone morphogenetic proteins in Saos-2 cells also may be dependent on the cell cycle.