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

IF 2.9 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Reinhard Gruber, Martin Schöfnagl, Florian Karreth, Michael B Fischer, Georg Watzek
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引用次数: 5

Abstract

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.

稳定的类似物碳环TXA2而不是血小板释放的TXA2诱导破骨细胞样细胞的形成。
凝血酶A(2) (TXA(2))是活化血小板花生四烯酸代谢的主要产物。血小板释放上清(PRS)可以通过nf - kb配体(RANKL)依赖的环氧化酶(COX)/受体激活剂途径诱导小鼠骨髓培养中破骨细胞样细胞的形成。在这里,我们研究了血小板释放的TXA(2)与破骨细胞生成之间的可能联系。TXA的稳定类似物(2),碳环TXA(2) (CTXA(2))可以通过rankl依赖性途径诱导小鼠骨髓培养物中耐酒石酸酸性磷酸酶阳性多核细胞的形成,并且需要基质细胞的存在。有趣的是,血小板释放的不稳定的TXA(2)不能解释破骨细胞的作用,因为:(a)在TXA(2)受体拮抗剂SQ29548存在时,prs诱导的破骨细胞发生;(b)吲哚美辛和乙酰水杨酸对血小板TXA(2)合成的抑制作用未能降低相应上清的破骨潜能;(c) CTXA(2)诱导的不依赖于吲哚美辛和选择性COX-2抑制剂NS398的破骨细胞样细胞形成。
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来源期刊
CiteScore
6.40
自引率
6.70%
发文量
60
审稿时长
13.2 weeks
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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