EXPRESSION OF CELL-GROWTH AND BONE PHENOTYPIC GENES DURING THE CELL-CYCLE OF NORMAL DIPLOID OSTEOBLASTS AND OSTEOSARCOMA CELLS

Establishing regulatory mechanisms that mediate proliferation of osteo blasts while restricting expression of genes associated with mature bo ne cell phenotypic properties to post-proliferative cells is fundament al to understanding skeletal development. To gain insight into relatio nships between growth control and the developmental expression of gene s during osteoblast differentiation, we have examined expression of th ree classes of genes during the cell cycle of normal diploid rat calva rial-derived osteoblasts and rat osteosarcoma cells (ROS 17/2.8): cell cycle and growth-related genes (e.g., histone), genes that encode maj or structural proteins (e.g., actin and vimentin), and genes related t o the biosynthesis, organization, and mineralization of the bone extra cellular matrix (e.g., alkaline phosphatase, collagen I, osteocalcin, and osteopontin). In normal diploid osteoblasts as well as in osteosar coma cells we found that histone genes, required for cell progression, are selectively expressed during S phase. All other genes studied wer e constitutively expressed both at the transcriptional and posttranscr iptional levels. Alkaline phosphatase, an integral membrane protein in both osteoblasts and osteosarcoma cells, exhibited only minimal chang es in activity during the osteoblast and osteosarcoma cell cycles. Our findings clearly indicate that despite the loss of normal proliferati on-differentiation interrelationships in osteosarcoma cells, cell cycl e regulation or constitutive expression of growth and phenotypic genes is maintained. (C) 1994 Wiley-Liss, Inc.