Prostaglandin E2 causes a transient inhibition of mineral mobilization, matrix degradation, and lysosomal enzyme release from mouse calvarial bones in vitro.
The effect of prostaglandin E2 (PGE2) on the kinetic of bone resorption in vitro was assessed by following the release of minerals and degradation of matrix in cultured mouse calvarial bones. PGE2 (1 and 3 mumol/liter) caused an initial inhibition of the release of 45Ca, stable calcium, and inorganic phosphate from unstimulated calvarial bones. The effect was transient and after 24 and 48 hours the release of 45Ca, stable calcium, and inorganic phosphate from PGE2-treated bones was enhanced. 0.3 mumol/liter of PGE2 stimulated the release of 45Ca after 24 hours, but at this concentration no initial inhibition was observed. The initial inhibitory effect of PGE2 (1 mumol/liter) could be further increased by three structurally different inhibitors of cyclic AMP breakdown. PGE2 (1 mumol/liter) caused not only an initial inhibition of mineral release but also an initial inhibition of matrix degradation, as assessed by the release of 3H from [3H]-proline labeled bones. In addition, PGE2 (3 mumol/liter), in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, caused a rapid (6 hours) inhibition of the release of the lysosomal enzymes beta-glucuronidase and beta-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-induced 45Ca release. Nor did PGE2 inhibit the stimulation of radioactive calcium mobilization induced by 1 alpha (OH)-vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001857:Bone Matrix / Q000378:metabolism*; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone; D005966:Glucuronidase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D008903:Minerals / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology*
D008903:Minerals; D010281:Parathyroid Hormone; D010710:Phosphates; D011458:Prostaglandins E; C028815:salmon calcitonin; D002116:Calcitonin; D000242:Cyclic AMP; D005966:Glucuronidase; D015232:Dinoprostone; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine