Platelet activating factor increases intracellular calcium in isolated osteoclasts but does not modify bone resorption.
Platelet activating factor (PAF) is an inflammatory mediator secreted by activated macrophages and granulocytes. Since PAF has been previously demonstrated to increase intracellular calcium in isolated osteoclasts, the effect of PAF on bone resorption was examined. This was compared to effects seen after addition of calcium ionophores and calcitonin, an inhibitor of bone resorption, in order to determine if an increase in [Ca++]i inhibits osteoclast-mediated resorption. The results demonstrate that PAF has no effect on either unstimulated or PTH-induced bone resorption. Calcium ionophores, ionomycin, and A23187, at concentrations that increased [Ca++]i, failed to modulate resorption in the fetal long bone assay. In addition, salmon calcitonin did not change [Ca++]i in spite of its strong inhibition of bone resorption. Taken together, these results demonstrate that the second messenger pathways involved in osteoclast downregulation can be independent of [Ca++]i, and may involve other messenger systems.
Wucherpfennig
A L
AL
Forsyth Research Institute, Boston, MA 02115.
Dewhirst
F E
FE
Stashenko
P
P
D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology
D010281:Parathyroid Hormone; D010972:Platelet Activating Factor; D000001:Calcimycin; D015759:Ionomycin; D002118:Calcium