NDLI: TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption* ♦

Content Provider	PubMed Central
Author	Chamoux, Estelle Bisson, Martine Payet, Marcel Daniel Roux, Sophie
Abstract	Most of the signaling effectors located downstream of receptor activator of NF-κB (RANK) activation are calcium-sensitive. However, the early signaling events that lead to the mobilization of intracellular calcium in human osteoclasts are still poorly understood. The Ca2+-sensitive fluorescent probe Fura2 was used to detect changes in the intracellular concentration of Ca2+ ([Ca2+] i ) in a model of human osteoclasts. Stimulating these cells with receptor activator of NF-κB ligand (RANKL) induced a rapid and significant increase in [Ca2+] i . Adding extracellular Ca2+ chelators, depleting intracellular stores, and the use of a phospholipase C inhibitor all indicated that the Ca2+ was of extracellular origin, suggesting the involvement of a Ca2+ channel. We showed that none of the classical Ca2+ channels (L-, T-, or R-type) were involved in the RANKL-induced Ca2+ spike. However, the effect of high doses of Gd3+ did suggest that TRP family channels were present in human osteoclasts. The TRPV-5 channel was expressed in osteoclasts and was mainly located in the cellular area in contact with the bone surface. Furthermore, the RNA inactivation of TRPV-5 channel completely inhibited the RANKL-induced increase in [Ca2+] i , which was accompanied in the long term by marked activation of bone resorption. Overall, our results show that RANKL induced a significant increase in [Ca2+] i of extracellular origin, probably as a result of the opening of TRPV-5 calcium channels on the surface of human osteoclasts. Our findings suggest that TRPV-5 contributes to maintaining the homeostasis of the human skeleton via a negative feedback loop in RANKL-induced bone resorption.
Related Links	http://dx.doi.org/10.1074/jbc.m109.075234
Ending Page	25362
Page Count	9
Starting Page	25354
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	33
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-08-13
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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TRPV-5's RANK in the Calcium Chain♦ TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption

TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption

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TRPV-5 Mediates a Receptor Activator of NF-κB (RANK) Ligand-induced Increase in Cytosolic Ca2+ in Human Osteoclasts and Down-regulates Bone Resorption* ♦

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