The transient receptor potential channel TRPV6 is dynamically expressed in bone cells but is not crucial for bone mineralization in mice
The transient receptor potential channel TRPV6 is dynamically expressed in bone cells but is not crucial for bone mineralization in mice
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DOI：
10.1002/jcp.22923
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发表时间：
2012-05
影响因子：
5.6
通讯作者：
B. V. D. van der Eerden;P. Weissgerber;N. Fratzl-Zelman;J. Olausson;J. Hoenderop;M. Schreuders-koedam
中科院分区：
文献类型：
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作者：
B. V. D. van der Eerden;P. Weissgerber;N. Fratzl-Zelman;J. Olausson;J. Hoenderop;M. Schreuders-koedam
骨骼是体内钙离子的主要储存库，在钙离子稳态中起着重要的作用。在骨形成和骨吸收过程中，成骨细胞和破骨细胞必须分别向骨和破骨细胞转运钙离子。然而，人们对这些骨细胞中的钙离子运输机制知之甚少。在本研究中，我们检测了骨骼上皮细胞钙通道TRPV6。TRPV6mRNA在人和小鼠成骨样细胞、外周血单核细胞来源的人破骨细胞和小鼠的胫骨骨髓来源的破骨细胞中表达。其他跨细胞钙转运基因Calbindin-D9K和/或-D28K、Na+/Ca~(2+)交换器1和质膜Ca~(2+)-ATPase(PMCA1b)在这些类型的骨细胞中也有表达。人成骨细胞、破骨细胞和小鼠破骨细胞的免疫荧光和共聚焦显微镜显示，TRPV6蛋白位于成骨细胞的顶端，PMCA1b位于骨样结构域，而在破骨细胞中，TRPV6主要位于面向骨的部位。TRPV6在人成骨细胞中动态表达，在细胞外基质矿化过程中表达最强。1，25-二羟基维生素D3(1，25(OH)2D3)不改变矿化和非矿化SV-HFO培养物中TRPV6的表达。慢病毒转导介导的TRPV6在这些细胞中的过表达并没有改变矿化。Trpv6D541A/D541A小鼠的骨骼微结构和矿化没有受到影响，其中孔区的天冬氨酸541被丙氨酸取代，使TRPV6通道失去功能。综上所述，TRPV6和其他参与跨细胞钙离子转运的蛋白质在骨细胞中动态表达，而TRPV6似乎对小鼠的骨代谢和基质矿化不是至关重要的。J.细胞。物理。227：1951-1959,2012年。©2011 Wiley期刊，Inc.
Bone is the major store for Ca2+ in the body and plays an important role in Ca2+ homeostasis. During bone formation and resorption Ca2+ must be transported to and from bone by osteoblasts and osteoclasts, respectively. However, little is known about the Ca2+ transport machinery in these bone cells. In this study, we examined the epithelial Ca2+ channel TRPV6 in bone. TRPV6 mRNA is expressed in human and mouse osteoblast‐like cells as well as in peripheral blood mononuclear cell‐derived human osteoclasts and murine tibial bone marrow‐derived osteoclasts. Also other transcellular Ca2+ transport genes, calbindin‐D9k and/or ‐D28K, Na+/Ca2+ exchanger 1, and plasma membrane Ca2+ ATPase (PMCA1b) were expressed in these bone cell types. Immunofluorescence and confocal microscopy on human osteoblasts and osteoclasts and mouse osteoclasts revealed TRPV6 protein at the apical domain and PMCA1b at the osteoidal domain of osteoblasts, whereas in osteoclasts TRPV6 was predominantly found at the bone‐facing site. TRPV6 was dynamically expressed in human osteoblasts, showing maximal expression during mineralization of the extracellular matrix. 1,25‐Dihydroxyvitamin D3 (1,25(OH)2D3) did not change TRPV6 expression in both mineralizing and non‐mineralizing SV‐HFO cultures. Lentiviral transduction‐mediated overexpression of TRPV6 in these cells did not alter mineralization. Bone microarchitecture and mineralization were unaffected in Trpv6D541A/D541A mice in which aspartate 541 in the pore region was replaced with alanine to render TRPV6 channels non‐functional. In summary, TRPV6 and other proteins involved in transcellular Ca2+ transport are dynamically expressed in bone cells, while TRPV6 appears not crucial for bone metabolism and matrix mineralization in mice. J. Cell. Physiol. 227: 1951–1959, 2012. © 2011 Wiley Periodicals, Inc.