Reinhard Gruber, Martin Schöfnagl, Florian Karreth, Michael B Fischer, Georg Watzek
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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.
期刊介绍：
The role of lipids, including essential fatty acids and their prostaglandin, leukotriene and other derivatives, is now evident in almost all areas of biomedical science. Cell membrane behaviour and cell signalling in all tissues are highly dependent on the lipid constituents of cells. Prostaglandins, Leukotrienes & Essential Fatty Acids aims to cover all aspects of the roles of lipids in cellular, organ and whole organism function, and places a particular emphasis on human studies. Papers concerning all medical specialties are published. Much of the material is particularly relevant to the development of novel treatments for disease.
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