Platelet-activating factor stimulates resorption by rabbit osteoclasts in vitro.
We have shown previously that platelet-activating factor (PAF), a potent inflammatory mediator, acts directly on isolated rat osteoclasts to elevate cytosolic free Ca2+ concentration ([Ca2+]i). The purpose of this study was to examine the effects of PAF on osteoclast function. Osteoclasts were isolated from the long bones of neonatal rabbits and studied in three ways. [Ca2+]i of fura-2-loaded osteoclasts was monitored by microspectrofluorimetry. In 9 out of 16 cells tested, PAF (10-100 nM) caused elevation of [Ca2+]i that peaked then returned to baseline. In contrast, the biologically inactive precursor and metabolite of PAF, lyso-PAF, was without effect. Using time-lapse videomicroscopy, we found that PAF elicited retraction of peripheral pseudopods. Although calcitonin induced sustained retraction and immobility, the response to PAF was transient and, within 30 min, pseudopods reformed. To assess effects of PAF on resorptive activity, osteoclasts were cultured on dentin slices for 48 h in the presence of vehicle, PAF (200 nM), or calcitonin (100 ng/ml). PAF increased the area of individual resorption pits (from control values of 1,660 +/- 110 to 2,240 +/- 200 microns2, P < 0.05) and the total planar area resorbed per unit area of substrate (from 7.6 +/- 1.6 to 14.5 +/- 3.1 x 10(4) microns2/cm2, P < 0.025). As expected, calcitonin significantly decreased resorptive activity. These data indicate that PAF activates osteoclastic resorption. PAF may play a role in mediating the resorption of bone and mineralized cartilage in inflammatory diseases such as rheumatoid arthritis and periodontitis.
Zheng
Z G
ZG
Division of Oral Biology, Faculty of Dentistry, University of Western Ontario, London, Canada.
Wood
D A
DA
Sims
S M
SM
Dixon
S J
SJ
D000818:Animals; D001862:Bone Resorption; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011817:Rabbits
D010972:Platelet Activating Factor; D002118:Calcium