ASCORBATE CONCENTRATION IN OSTEOBLASTIC CELLS IS ELEVATED BY TRANSFORMING GROWTH-FACTOR-BETA

Transforming growth factor-beta modulates the proliferation, different iation, and synthetic activity of osteoblasts, but its mechanisms of a ction are not fully understood. Because ascorbate also influences oste oblast differentiation and is a cofactor for collagen synthesis, the p resent study examined the effect of transforming growth factor-beta on the initial rate of transport and steady-state concentration of ascor bate in an osteoblastic cell line. UMR-106 rat osteosarcoma cells accu mulated reduced vitamin C from culture medium. Virtually all accumulat ion of ascorbate was accomplished by a saturable Na+-dependent transpo rt mechanism. Transforming growth factor-beta increased the initial ra te of ascorbate transport, measured in either attached or suspended ce lls. Within 24 h, the growth factor also increased the steady-state in tracellular concentration of ascorbate, without significantly changing cell volume or the DNA or protein content of cultures. These data pro vide evidence that Na+-ascorbate cotransport activity controls ascorba te concentration in osteoblasts. Furthermore, the results indicate tha t both the transport rate and steady-state concentration of ascorbate in these cells are regulated by transforming growth factor-beta.