The effect of fluoride pretreatment and ascorbic acid on bone growth in tissue culture

The addition of ascorbic acid to tissue culture media was found to increase the collagen and mineral content of bones grown in vitro both effects resulting apparently from an increased rate of collagen synthesis. Ascorbic acid also increased the solubility of the bone collagen, possibly by increasing the accumulation of newly synthesized, soluble, collagen in the bone at a rate faster than the formation of crosslinkages between the collagen molecules. Pretreating bone in vitro with fluoride increased the weight of cultured bone primarily by increasing the mineral content. The effect was greatest in the presence of a low rate of collagen synthesis. When collagen synthesis was accelerated by ascorbic acid, fluoride pretreatment caused a lesser increase in bone mass and actually depressed collagen synthesis. It would appear, therefore, that the effect of fluoride pretreatment on bone growth is dependent in part on the rate of collagen synthesis by bone cells. Fluoride pretreatrnent decreased the solubility of the collagen matrix of bone indicating an affect on intermolecular crosslinking. The increased degree of crosslinking due to the fluoride pretreatment may account, in part, for the inhibition of bone resorption in tissue culture.