The stable analog carbocyclic TXA2 but not platelet-released TXA2 induces osteoclast-like cell formation.
Thromboxan A(2) (TXA(2)) is the main product of arachidonic acid metabolism in activated platelets. Platelet-released supernatants (PRS) can induce osteoclast-like cell formation in murine bone marrow cultures via a cyclooxygenase (COX)/receptor activator of NF-kB-ligand (RANKL)-dependent pathway. Here we investigated a possible linkage between platelet-released TXA(2) and osteoclastogenesis. The stable analog of TXA(2), carbocyclic TXA(2) (CTXA(2)) can induce the formation of tartrate-resistant acid phosphatase positive multinucleated cells in murine bone marrow cultures via a RANKL-dependent pathway and requires the presence of stromal cells. Interestingly, the platelet-released instable TXA(2) does not account for osteoclastogenic effects as: (a) PRS-induced osteoclastogenesis in the presence of the TXA(2) receptor antagonist SQ29548; (b) inhibition of platelet TXA(2) synthesis by indomethacin and acetylsalicylic acid failed to decrease the osteoclastogenic potential of the corresponding supernatants; and (c) CTXA(2)-induced osteoclast-like cell formation independent of indomethacin and the selective COX-2 inhibitor NS398.
Gruber
Reinhard
R
Department of Oral Surgery, School of Dentistry, University of Vienna, Waehringerstrasse 25a, Austria. reinhard.gruber@akh-wien.ac.at
Schöfnagl
Martin
M
Karreth
Florian
F
Fischer
Michael B
MB
Watzek
Georg
G
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D001854:Bone Marrow Cells; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009578:Nitrobenzenes / Q000494:pharmacology; D010010:Osteoclasts / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D017154:Stromal Cells / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D013644:Tartrates / Q000494:pharmacology; D013928:Thromboxane A2 / Q000737:chemistry* / Q000494:pharmacology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D016861:Cyclooxygenase Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008562:Membrane Glycoproteins; D009578:Nitrobenzenes; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D013449:Sulfonamides; D013644:Tartrates; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016718:Arachidonic Acid; D013928:Thromboxane A2; C045749:SQ 29548; D011451:Prostaglandin-Endoperoxide Synthases; D000135:Acid Phosphatase; D001241:Aspirin; C029768:tartaric acid; D007213:Indomethacin