期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：48
页码：17507-17512
DOI：10.1073/pnas.0505789102
语种：English
出版社：The National Academy of Sciences of the United States of America
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 TRPV5 is one of the most Ca2+-selective transient receptor potential (TRP) channels. In this study, the functional role of TRPV5 in bone was investigated. TRPV5 mRNA was expressed in human and murine bone samples and in osteoclasts along with other genes involved in transcellular Ca2+ transport, including calbindin-D9K and calbindin-D28K, 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 deoxypyridinoline 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, TRPV5 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.
