Colchicine stimulation of hyaluronate synthesis and secretion in bone organ culture

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Abstract
Parathyroid hormone (PTH) is known to have a number of effects on bone tissue in vitro, including the stimulation of calcium release and the synthesis and turnover of hyaluronate. PTH‐stimulated calcium release is inhibited by colchicine. Since hyaluronate may play a role in demineralization, calcium release into the media as a measure of bone resorption was correlated with the synthesis and secretion of 3H‐glucosamine‐labeled macromolecules. Newborn mice were labeled with 45Ca, and the calvaria removed and incubated in vitro in media containing 3H‐glucosamine. Addition of colchicine to the culture media inhibited the release of 45Ca into the media while stimulating the synthesis and secretion of 3H‐glucosamine labeled macromolecules. DEAE‐cellulose chromatography resolved the labeled macromolecular material into four peaks, of which the third peak containing hyaluronate demonstrated approximately twice the amount of radioactivity. PTH stimulation of calcium release was inhibited likewise by colchicine, while 3H‐glucosamine incorporation into labeled macromolecules was stimulated. Short term labeling studies emphasized the marked stimulatory effect that both PTH and colchicine have on the incorporation of 3H‐glucosamine into hyaluronate. PTH stimulated the incorporation of 35S‐sulfate, while colchicine markedly inhibited its incorporation into non‐dialyzable material. Both PTH and colchicine inhibited protein synthesis. Based on the observations, colchicine appears to stimulate the synthesis and secretion of hyaluronate and alter a number of metabolic pathways. Hyaluronate does not appear to be directly involved in the demineralization process.