Bone-resorbing osteoclasts contain gap-junctional connexin-43

Bone-resorbing osteoclasts contain gap-junctional connexin-43
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DOI:
10.1359/jbmr.2000.15.5.919
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发表时间:
2000-05-01
影响因子:
6.2
通讯作者:
Tuukkanen, J
Tuukkanen, J
中科院分区:
医学1区
文献类型:
--
作者:
Ilvesaro, J;Väänänen, K;Tuukkanen, J

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先前已经描述了细胞间间隙连接位于表面成骨细胞之间、成骨细胞与下面的骨细胞之间以及骨小管中的骨细胞细胞突起之间的接触位点。间隙连接通道的亚基由称为连接蛋白的蛋白质家族组装而成。在目前的工作中,我们表明在牛骨切片上培养的大鼠破骨细胞显示出连接蛋白-43(Cx43)染色,定位于细胞与细胞接触处的细胞质膜中以及细胞间接触的细胞质膜中。破骨细胞的基底外侧膜。使用充分表征的凹坑形成测定研究了庚醇(一种已知的间隙连接抑制剂)的作用。庚醇降低了破骨细胞的数量和活性,庚醇处理后,单核抗酒石酸酸性磷酸酶(TRAP)阳性细胞占所有TRAP阳性细胞的比例增加,表明单核破骨细胞前体与多核成熟破骨细胞的融合存在缺陷。此外,庚醇处理的培养物中总吸收面积和吸收坑数量也减少。这些结果表明间隙连接Cx43在破骨细胞中发挥功能性作用,间隙连接的阻断会降低破骨细胞的数量和活性。这可以表明多核破骨细胞和单核细胞之间通过间隙连接直接通讯,或者通过成骨细胞之间的间隙连接产生间接影响。
Intercellular gap junctions have been previously described at contact sites between surface osteoblasts, between osteoblasts and underlying osteocytes, and between osteocyte cell processes in the canaliculi, The subunits of gap junction channels are assembled from a family of proteins called connexins, In the present work, we show that rat osteoclasts cultured on bovine bone slices show connexin-43 (Cx43) staining localizing in the plasma membrane of the cells in cell-cell contacts and over the basolateral membrane of osteoclasts. The effect of heptanol, a known gap-junctional inhibitor, was studied using the well-characterized pit formation assay. Heptanol decreased the number and activity of osteoclasts, The proportion of mononuclear tartrate-resistant acid phosphatase (TRAP)-positive cells out of all TRAP-positive cells increased on heptanol treatment, suggesting a defect in the fusion of mononuclear osteoclast precursors to multinucleated mature osteoclasts, Furthermore, the total resorbed area and the number of resorption pits also decreased in the heptanol-treated cultures. These results suggest that gap-junctional Cx43 plays a functional role in osteoclasts and that the blocking of gap junctions decreases both the number and the activity of osteoclasts, This can indicate both a direct communication between multinucleated osteoclasts and mononuclear cells through gap junctions or an indirect effect through gap junctions between osteoblasts.