Protamine: A powerfulin vivo inhibitor of bone resorption

Heparin in combination with suboptimal concentrations of parathyroid hormone (PTH) has been shown to stimulate calcium release from bone organ cultures. The mechanism of action of heparin, however, is not known. One possible mechanism relates to the highly sulfated structure of heparin. We have compared heparin to other glycosaminoglycans to stimulate calcium release from mouse calvarial organ cultures in the presence and absence of suboptimal concentrations of parathyroid hormone. The exogenous addition of heparin to bone cultures demonstrated only slight effects on calcium release at 5.0, 10, and 100 micrograms/ml. The addition of hyaluronic acid to the calvarial cultures caused a significant release of calcium at 10 and 100 micrograms/ml compared to 5 micrograms/ml hyaluronic acid. Dermatan sulfate was equally as effective as hyaluronic acid at 100 micrograms/ml but not at 10 micrograms/ml. A comparison of heparin- and hyaluronic acid-stimulated release demonstrated a significantly greater amount of calcium release with hyaluronic acid 100 micrograms/ml. At 5.0 and 10 micrograms/ml, there was no difference between heparin and hyaluronic acid in the amount of calcium released into the culture medium. When heparin was added to the organ cultures with suboptimal concentrations of PTH, there was a significant enhancement of calcium release observed with 10 and 100 micrograms/ml heparin compared to heparin addition alone. When hyaluronic acid was added with suboptimal concentrations of PTH, no significant enhancement of calcium release was observed with 100 micrograms/ml hyaluronic acid. Dermatan sulfate, chondroitin sulfates A and C, and keratan sulfate, in combination with PTH, stimulated significant calcium release compared to the glycosaminoglycan added alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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