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Prostaglandin E2 causes a transient inhibition of mineral mobilization, matrix degradation, and lysosomal enzyme release from mouse calvarial bonesIn Vitro

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Summary

The effect of prostaglandin E2 (PGE2) on the kinetic of bone resorptionin vitro was assessed by following the release of minerals and degradation of matrix in cultured mouse calvarial bones. PGE2 (1 and 3 μmol/liter) caused an initial inhibition of the release of45Ca, stable calcium, and inorganic phosphate from unstimulated calvarial bones. The effect was transient and after 24 and 48 hours the release of45Ca, stable calcium, and inorganic phosphate from PGE2-treated bones was enhanced. 0.3 μmol/liter of PGE2 stimulated the release of45Ca after 24 hours, but at this concentration no initial inhibition was observed. The initial inhibitory effect of PGE2 (1 μmol/liter) could be further increased by three structurally different inhibitors of cyclic AMP breakdown. PGE2 (1 μmol/liter) caused not only an initial inhibition of mineral release but also an initial inhibition of matrix degradation, as assessed by the release of3H from [3H]-proline labeled bones. In addition, PGE2 (3 μmol/liter), in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, caused a rapid (6 hours) inhibition of the release of the lysosomal enzymes β-glucuronidase and β-N-acetyl-glucosaminidase, without affecting the release of the cytosolic enzyme lactate dehydrogenase. Similar specific initial inhibition of lysosomal enzyme release was also seen in the presence of calcitonin and dibutyryl cyclic AMP, but not in the presence of parathyroid hormone (PTH). Neither PGE2 nor the phosphodiesterase inhibitors rolipram and Ro 20.1724, could inhibit the initial stages of PTH-induced45Ca release. Nor did PGE2 inhibit the stimulation of radioactive calcium mobilization induced by 1α(OH)-vitamin D3. Enhancement of cyclic AMP formation by forskolin, choleratoxin, and dibutyryl cyclic AMP in unstimulated bones resulted in an initial reduction of45Ca release (6 hours) followed by a delayed stimulation (96 hours). These data indicate that PGE2 has the capacity to reduce the activity of unstimulated, preexisting osteoclasts by a cyclic AMP-dependent process.

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Authors and Affiliations

  1. Department of Oral Pathology, University of Ume⇘, S-901 87, Umeå, Sweden

    Ulf H. Lerner, Maria Ransjö & Östen Ljunggren

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  1. Ulf H. Lerner
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  2. Maria Ransjö
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  3. Östen Ljunggren
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Lerner, U.H., Ransjö, M. & Ljunggren, Ö. Prostaglandin E2 causes a transient inhibition of mineral mobilization, matrix degradation, and lysosomal enzyme release from mouse calvarial bonesIn Vitro . Calcif Tissue Int 40, 323–331 (1987). https://doi.org/10.1007/BF02556694

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  • DOI: https://doi.org/10.1007/BF02556694

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