The stable analog carbocyclic TXA2 but not platelet-released TXA2 induces osteoclast-like cell formation

Thromboxan A₂ (TXA₂) 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 TXA₂ and osteoclastogenesis. The stable analog of TXA₂, carbocyclic TXA₂ (CTXA₂) 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 TXA₂ does not account for osteoclastogenic effects as: (a) PRS-induced osteoclastogenesis in the presence of the TXA₂ receptor antagonist SQ29548; (b) inhibition of platelet TXA₂ synthesis by indomethacin and acetylsalicylic acid failed to decrease the osteoclastogenic potential of the corresponding supernatants; and (c) CTXA₂-induced osteoclast-like cell formation independent of indomethacin and the selective COX-2 inhibitor NS398.