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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption
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The epithelial Ca2+ channel TRPV5 is essential for proper osteoclastic bone resorption

机译：上皮Ca2 +通道TRPV5对于适当的破骨细胞骨吸收至关重要

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摘要

Bone remodeling involves the interplay of bone resorption and formation and is accurately controlled to maintain bone mass. Both processes require transcellular Ca2+ transport, but the molecular mechanisms engaged remain largely elusive. The epithelial Ca2+ channel TRIPV5 is one of the most Ca2+-selective transient receptor potential (TRP) channels. In this study, the functional role of TRPV5 in bone was investigated. TRIPV5 mRNA was expressed in human and murine bone samples and in osteoclasts along with other genes involved in transcellular Ca2+ transport, including calbinclin-D-9K and calbindin-D-28K, Na+/Ca2+ exchanger 1, and plasma membrane Ca2+-ATPase 1b. TRPV5 expression in murine osteoclasts was confirmed by immunostaining and showed predominant localization to the ruffled border membrane. However, TRPV5 was absent in osteoblasts. Analyses of femoral bone sections from TRPV5 knockout (TRPV5(-/-)) mice revealed increased osteoclast numbers and osteoclast area, whereas the urinary bone resorption marker deoxypyriclinoline was reduced compared with WT (TRPV5(+/+)) mice. In an in vitro bone marrow culture system, the amount of osteoclasts and number of nuclei per osteoclast were significantly elevated in TRPV5(-/-) compared with TRPV5(+/+) mice. However, using a functional resorption pit assay, we found that bone resorption was nearly absent in osteoclast cultures from TRPV5(-/-) mice, supporting the impaired resorption observed in vivo. In conclusion, TRIPV5 deficiency leads to an increase in osteoclast size and number, in which Ca2+ resorption is nonfunctional. This report identifies TRPV5 as an epithelial Ca2+ channel that is essential for osteoclastic bone resorption and demonstrates the significance of transcellular Ca2+ transport in osteoclastic function.
机译：骨骼重塑涉及骨骼吸收和形成的相互作用，并受到精确控制以维持骨骼质量。这两个过程都需要跨细胞的Ca2 +转运，但是所参与的分子机制仍然很难捉摸。上皮Ca2 +通道TRIPV5是最具有Ca2 +选择性的瞬时受体电势（TRP）通道之一。在这项研究中，TRPV5在骨骼中的功能作用进行了调查。 TRIPV5 mRNA在人和鼠骨样品中以及在破骨细胞中以及其他与跨细胞Ca2 +转运有关的基因中表达，包括calbinclin-D-9K和calbindin-D-28K，Na + / Ca2 +交换子1和质膜Ca2 + -ATPase 1b。免疫染色证实了鼠破骨细胞中TRPV5的表达，并表明其主要定位在褶皱的边界膜上。但是，成骨细胞中不存在TRPV5。从TRPV5基因敲除（TRPV5（-/-））小鼠的股骨切片分析显示破骨细胞数量和破骨细胞面积增加，而与WT（TRPV5（+ / +））小鼠相比，尿中骨吸收标记脱氧吡啶啉的含量降低。在体外骨髓培养系统中，与TRPV5（+ / +）小鼠相比，TRPV5（-/-）中破骨细胞的数量和每个破骨细胞的核数显着增加。但是，使用功能性吸收坑测定法，我们发现从TRPV5（-/-）小鼠的破骨细胞培养物中几乎没有骨吸收，从而支持了体内观察到的吸收受损。总之，TRIPV5缺乏导致破骨细胞的大小和数量增加，其中Ca2 +吸收无效。该报告确定TRPV5为上皮Ca2 +通道，对破骨细胞的骨吸收至关重要，并证明了跨细胞Ca2 +转运在破骨细胞功能中的重要性。

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