The transient receptor potential channel TRPV6 is dynamically expressed in bone cells but is not crucial for bone mineralization in mice

✍ Scribed by Bram C.J. van der Eerden; Petra Weissgerber; Nadja Fratzl-Zelman; Jenny Olausson; Joost G.J. Hoenderop; Marijke Schreuders-Koedam; Marco Eijken; Paul Roschger; Teun J. de Vries; Hideki Chiba; Klaus Klaushofer; Veit Flockerzi; René J.M. Bindels; Marc Freichel; Johannes P.T.M. van Leeuwen

• Book ID: 102313139
• Publisher: John Wiley and Sons
• Year: 2012
• Tongue: English
• Weight: 312 KB
• Volume: 227
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.22923

✦ Synopsis

Bone is the major store for Ca 2þ in the body and plays an important role in Ca 2þ homeostasis. During bone formation and resorption Ca 2þ must be transported to and from bone by osteoblasts and osteoclasts, respectively. However, little is known about the Ca 2þ transport machinery in these bone cells. In this study, we examined the epithelial Ca 2þ 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 Ca 2þ transport genes, calbindin-D 9k and/or -D 28K , Na þ /Ca 2þ exchanger 1, and plasma membrane Ca 2þ 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 D 3 (1,25(OH) 2 D 3 ) 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 Trpv6 D541A/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 Ca 2þ transport are dynamically expressed in bone cells, while TRPV6 appears not crucial for bone metabolism and matrix mineralization in mice.