Stimulation of bone resorption by lipoxygenase metabolites of arachidonic acid.
We have studied the effect of leukotrienes, (LT): B4, C4, D4 and E4 and the hydroxyeicosatetraenoic acids (HETEs) 5-HETE and 12-HETE on bone resorption in vitro. Resorption was measured by colorimetric assay of calcium released from neonatal mouse calvaria maintained in organ culture for 72h. All the LTs and HETEs stimulated bone resorption, with optimum responses at picomolar or nanomolar concentrations. The responses were biphasic, with a decreasing effect at higher concentrations. In contrast, prostaglandin E2 (PGE2) stimulated resorption only at 10nM and above. Indomethacin partially inhibited resorption by LTB4, LTC4 and LTD4, but did not affect resorption stimulated by LTE4, 5-HETE and 12-HETE. These results indicate that lipoxygenase products of arachidonic acid are highly potent bone resorbing factors and may play an important role in the localised bone loss associated with inflammatory lesions.
Meghji
S
S
Joint Department of Oral and Maxillo-Facial Surgery, University College, London, U.K.
Sandy
J R
JR
Scutt
A M
AM
Harvey
W
W
Harris
M
M
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001862:Bone Resorption / Q000187:drug effects*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D017999:Leukotriene E4; D015289:Leukotrienes / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D051379:Mice; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D017999:Leukotriene E4; D008084:Lipoxygenase; D007213:Indomethacin