ATP as an osteoclast regulator?
ATP as an osteoclast regulator?
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DOI：
10.1111/j.1469-7793.1997.236bh.x
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发表时间：
1997-09-01
影响因子：
5.5
通讯作者：
King, BF
中科院分区：
文献类型：
--
作者：
Arnett, TR;King, BF
这些发现对破骨细胞的最终功能，即骨吸收有什么意义？Weidema et al.（1997）和Yu & Ferrier（1995）来源于在玻璃表面而不是骨和牙本质表面上培养的破骨细胞。Weidema et al.（1997）主要在被认为是活性破骨细胞特征的圆形表型的细胞上制备，但这些细胞明显缺乏与再吸收相关的极化和活性质子泵送。尚不清楚Yu和Ferrier（1995）报告的响应ATP的pH值降低是否与H+可渗透的非选择性（P2X型）阳离子通道的瞬时打开和Weidema等人描述的瞬时内向电流有关。（1997年）或其他现象。在缺乏数据的情况下，很容易推测，ATP引起的pHI降低可能有利于再吸收坑的形成，如果一个合适的矿化底物已经存在，通过促进H+的挤出。根据这一论点，这些现象可能只是短暂的非极化细胞，不积极挤出H+。P2X受体是否可能参与了细胞内重吸收所需的H+供应的门控？有一些诱人的暗示。最近的数据表明，重组P2X2受体被细胞外酸化致敏，pH激活特征（King et al. 1996）使人想起H+对破骨细胞形成小窝的强大刺激作用。Nordstrom等人的实验提供了破骨细胞中H+刺激的H+选择性电导的独立证据。（1995年）。Weidema等人（1997）为理解细胞外核苷酸在调节破骨细胞膜电流和功能中的作用提供了重要的新线索。希望与骨或牙本质表面（不透明、富含钙且自发荧光）上的破骨细胞（活跃吸收或其他）的膜片钳和离子成像相关的一些技术困难可能很快就会被克服。
What might be the implications of these findings for the ultimate function of osteoclasts, ie bone resorption? The data of Weidema et al.(1997) and Yu & Ferrier (1995) were derived from osteoclasts cultured on glass surfaces rather than bone and dentine surfaces. The observations by Weidema et al.(1997) were made predominantly on cells of a rounded phenotype thought to be characteristic of active osteoclasts, but such cells obviously lack the polarization and active proton pumping associated with resorption. It is unclear whether the pH, decrease reported by Yu & Ferrier (1995) in response to ATP is related to the transient opening of a non-selective (P2X-type) cation channel permeable to H+ and the transient inward current described by Weidema et al.(1997) or to other phenomena. In the absence of data, it is tempting to speculate that an ATP-elicited pHI decrease might favour resorption-pit formationif a suitable mineralized substrate had been present-by facilitating the extrusion of H+. Following this argument, these phenomena might be expected to be only transient in non-polarized cells that were not actively extruding H+. Is it possible that P2X receptors could be involved in gating some of the intracellular supply of H+ needed for resorption? There are some tantalizing hints. Recent data show that recombinant P2X2 receptors are sensitized by extracellular acidification, with a pH-activation profile (King et al. 1996) reminiscent of the powerful stimulatory action of H+ on pit formation by osteoclasts. Independent evidence for a H+-stimulated H+-selective conductance in osteoclasts is provided by the experiments of Nordstrom et al.(1995). Weidema et al.(1997) have provided important new clues to under-standing the role for extracellular nucleotides in modulating osteoclast membrane currents and function. Hopefully, some of the technical difficulties associated with patch clamping and ion imaging of osteoclasts (actively resorbing or otherwise) on bone or dentine surfaces (which are opaque, calcium rich and autofluorescent) might soon be overcome.