Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors
Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors
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DOI：
10.1074/jbc.m104608200
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Steinberg, TH
中科院分区：
文献类型：
--
作者：
Jorgensen, NR;Henriksen, Z;Steinberg, TH
成骨细胞和成骨细胞之间的信号传导在骨稳态中是重要的。我们以前发现，人成骨细胞通过两种机制传播细胞间钙信号：P2 Y受体的自分泌激活和缝隙连接通讯。在当前的工作中，我们确定了成骨细胞和破骨细胞之间以及破骨细胞之间机械诱导的细胞间钙信号传导。破骨细胞的细胞间钙反应需要P2受体激活，但不需要缝隙连接通讯。药理学研究和逆转录-PCR扩增表明，人类破骨细胞表达功能性P2 Y1受体，但出乎意料的是，脱敏P2 Y1并没有阻止钙信号传导到破骨细胞。我们还发现，破骨细胞表达功能性P2 X7受体，并表明这些受体的药理学抑制阻断钙信号传导到破骨细胞。因此，这些研究表明，成骨细胞和破骨细胞之间的钙信号传导通过P2受体的激活发生，但这两种细胞类型中的钙信号传导需要不同家族的P2受体。因此，骨细胞之间的细胞间钙信号传导适合于仅特异性影响骨形成或骨吸收细胞的药理学操作。P2受体可能是调节骨转换的重要药物靶点。
Signaling between osteoblasts and osteoblasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. Intercellular calcium responses in osteoclasts required P2 receptor activation but not gap junctional communication. Pharmacological studies and reverse transcriptase-PCR amplification demonstrated that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling to osteoclasts. Thus these studies show that calcium signaling between osteoblasts and osteoclasts occurs via activation of P2 receptors, but that different families of P2 receptors are required for calcium signaling in these two cell types. Intercellular calcium signaling among bone cells is therefore amenable to pharmacological manipulation that will specifically affect only bone-forming or bone-resorbing cells. P2 receptors may be important drug targets for the modulation of bone turnover.