Title: TRPV4-mediated calcium influx regulates terminal differentiation of osteoclasts
Authors: Masuyama, Ritsuko ×
Vriens, Joris
Voets, Thomas
Karashima, Yuji
Owsianik, Grzegorz
Vennekens, Rudi
Lieben, Liesbet
Torrekens, Sophie
Moermans, Karen
Vanden Bosch, An
Bouillon, Roger
Nilius, Bernd
Carmeliet, Geert #
Issue Date: Sep-2008
Publisher: Cell Press
Series Title: Cell Metabolism vol:8 issue:3 pages:257-265
Abstract: Calcium signaling controls multiple cellular functions and is regulated by the release from internal stores and entry from extracellular fluid. In bone, osteoclast differentiation is induced by RANKL (receptor activator of NF-kappaB ligand)-evoked intracellular Ca(2+) oscillations, which trigger nuclear factor-activated T cells (NFAT) c1-responsive gene transcription. However, the Ca(2+) channels involved remain largely unidentified. Here we show that genetic ablation in mice of Trpv4, a Ca(2+)-permeable channel of the transient receptor potential (TRP) family, increases bone mass by impairing bone resorption. TRPV4 mediates basolateral Ca(2+) influx specifically in large osteoclasts when Ca(2+) oscillations decline. TRPV4-mediated Ca(2+) influx hereby secures intracellular Ca(2+) concentrations, ensures NFATc1-regulated gene transcription, and regulates the terminal differentiation and activity of osteoclasts. In conclusion, our data indicate that Ca(2+) oscillations and TRPV4-mediated Ca(2+) influx are sequentially required to sustain NFATc1-dependent gene expression throughout osteoclast differentiation, and we propose TRPV4 as a therapeutic target for bone diseases.
ISSN: 1550-4131
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Laboratory of Ion Channel Research
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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