Effect of prostaglandin endoperoxides and metabolites on bone resorption in vitro

PROSTAGLANDINS are potent bone resorbers 1 which have been implicated as mediators of bone loss and hypercalcaemia in disease 2–6 , but the specific products in the pathway of prostaglandin synthesis and degradation which are responsible have not yet been identified in vivo . Although PGE 2 is the m...

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Veröffentlicht in:Nature (London) 1977, Vol.267 (5611), p.532-534
Hauptverfasser: RAISZ, LAWRENCE G, DIETRICH, JOHN W, SIMMONS, HOLLIS A, SEYBERTH, HANNSJOERG W, HUBBARD, WALTER, OATES, JOHN A
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Sprache:eng
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Zusammenfassung:PROSTAGLANDINS are potent bone resorbers 1 which have been implicated as mediators of bone loss and hypercalcaemia in disease 2–6 , but the specific products in the pathway of prostaglandin synthesis and degradation which are responsible have not yet been identified in vivo . Although PGE 2 is the most potent stimulator of bone resorption among the prostaglandins thus far tested in vitro 1 , in animal tumour models, the increase in immunoreactive PGE 2 concentrations does not correlate well with the development of hypercalcaemia 2 . We therefore tested the early products of arachidonic acid metabolism via the cyclo-oxygenase pathway, the prostaglandin endoperoxides (PGG 2 and PGH 2 ) and some of the 13,14-dihydro (H-PGE 2 and Ha-PGE 2 ) and 15-keto-13,14-dihydro metabolites of prostaglandins (15K-H 2 -PGE 2 and 15K-H-PGF 2α ) for their effects on the release of previously incorporated 45 Ca from cultured foetal rat long bones. The endoperoxides were found to cause a rapid transient increase in the release of previously incorporated 45 Ca from bone, but did not stimulate prolonged resorption. H 2 -PGE 2 and H 2 -PGE 1 were almost as potent as the parent compounds. 15K-H 2 -PGE 2 and 15K-H-PGF 2α were much less potent, but did stimulate resorption at 10 −5 M.
ISSN:0028-0836
1476-4687
DOI:10.1038/267532a0