Modulation of bone resorption by glycosaminoglycans: Effects of parathyroid hormone and interleukin-1

Regulation of calcium release from mouse calvariae by glycosaminoglycans and known modulators of bone resorption has been examined. Anticoagulant and nonanticoagulant fragments of heparin were combined with parathyroid hormone (PTH) and interleukin-1, beta (IL1), and calcium release from radiolabeled bone was determined. Three heparin fragments, dextran and dextran sulfate, when tested alone, released similar amounts of calcium as did native heparin alone. Suboptimal concentrations of PTH combined with heparin fragments of varying amounts of anticoagulant activity released similar amounts of calcium as did native heparin. When dextran or dextran sulfate was combined with PTH, the amount of calcium released was significantly greater than dextran or dextran sulfate alone but not from PTH when tested alone. Heparin, in combination with 0.1 μ/ml IL1, stimulated significant calcium release compared to heparin but not to IL1 tested alone. There was no significant difference in calcium release when hyaluronic acid in combination with 0.1 U/ml IL1 was compared to the amount of calcium released by either agent alone. Two of the heparin fragments combined with 0.l U/ml IL1 significantly inhibited calcium release compared to IL1 alone. In combination with 1.0 U/ml of IL1, heparin and hyaluronic acid inhibited calcium release compared to IL1 alone but this inhibition was not significant. The heparin fragments, combined with 1.0 U/ml IL1, had decreasing inhibitory activity as the degree of anticoagulant activity deceased. A comparison of glycosaminoglycan-modulated calcium release in mouse calvariae to that released in mouse radii/ulnae revealed consistantly greater percentages of calcium release from calvariae. The results of this study indicate that complex interactions exist between bone modulating substances and that structure-function relationships are important in determining positive or negative influences on bone metabolism.