Multinucleated osteoclast formation in vivo and in vitro by P2X7 receptor-deficient mice
Multinucleated osteoclast formation in vivo and in vitro by P2X7 receptor-deficient mice
复制标题
DOI：
10.1615/critreveukaryotgeneexpr.v13.i24.150
复制
发表时间：
2003-01-01
影响因子：
1.6
通讯作者：
Gallagher, JA
中科院分区：
文献类型：
--
作者：
Gartland, A;Buckley, KA;Gallagher, JA
P2X(7)受体是P2X嘌呤能受体家族的一员，经持续激活后在质膜上形成大孔。在造血来源的细胞中，P2X(7)受体的激活已被证明导致多个下游事件，包括细胞因子释放、细胞通透性和细胞凋亡。该受体还与多核巨细胞、多核细胞和破骨细胞的产生有关。我们最近已经证明，在体外，阻断这种受体可以抑制破骨细胞的形成；因此，我们在骨骼的背景下检查了缺乏P2X(7)受体的小鼠。这些小鼠是健康的，没有明显的骨骼问题。此外，我们能够证明它们在体内和体外形成多核细胞的能力，特别是破骨细胞。我们还证明了在体外，在毛霉毒素(MTX)刺激下，P2X(7)R(-/-)多核破骨细胞能够在质膜上形成孔洞。这些发现与破骨细胞前体细胞中存在内源性孔隙结构是一致的，这种结构可以被P2X(7)受体激活，或者在没有P2X(7)受体的情况下，通过不同的信号来介导融合和孔隙形成。这些数据为进一步了解P2X(7)受体的作用模式提供了依据。
: The P2X(7) receptor is a member of the family of P2X purinergic receptors, which upon sustained activation forms large pores in the plasma membrane. In cells of hematopoietic origin, P2X(7) receptor activation has been shown to lead to multiple downstream events, including cytokine release, cell permeabilization, and apoptosis. This receptor has also been implicated in the generation of multinucleated giant cells, polykaryons, and osteoclasts. We have recently demonstrated that a blockade of this receptor inhibits osteoclast formation in vitro; therefore, we examined mice deficient in the P2X(7) receptor in the context of bone. These mice were healthy and displayed no overt skeletal problems. Furthermore, we were able to demonstrate their ability to form multinucleated cells, in particular osteoclasts, both in vivo and in vitro. We also demonstrate the ability of P2X(7)R(-/-) multinucleated osteoclasts, upon stimulation with maitotoxin (MTX), to form pores in the plasma membrane in vitro. These findings are consistent with the existence of an endogenous pore structure present in osteoclast precursor cells that can be activated either by the P2X(7) receptor, or in its absence, by alternative signals to mediate fusion and pore formation. These data provide further insight into the mode of action of the P2X(7) receptor.