Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction
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Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction. / Kringelbach, Tina M.; Aslan, Derya; Novak, Ivana; Ellegaard, Maria; Syberg, Susanne; Andersen, Christina K.B.; Kristiansen, Kim A.; Vang, Ole; Schwarz, Peter; Jørgensen, Niklas R.
In: Cellular Signalling, Vol. 27, No. 12, 2015, p. 2401-2409.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Fine-tuned ATP signals are acute mediators in osteocyte mechanotransduction
AU - Kringelbach, Tina M.
AU - Aslan, Derya
AU - Novak, Ivana
AU - Ellegaard, Maria
AU - Syberg, Susanne
AU - Andersen, Christina K.B.
AU - Kristiansen, Kim A.
AU - Vang, Ole
AU - Schwarz, Peter
AU - Jørgensen, Niklas R.
N1 - Copyright © 2015 Elsevier Inc. All rights reserved.
PY - 2015
Y1 - 2015
N2 - Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.
AB - Osteocytes are considered the primary mechanosensors of bone, but the signaling pathways they apply in mechanotransduction are still incompletely investigated and characterized. A growing body of data strongly indicates that P2 receptor signaling among osteoblasts and osteoclasts has regulatory effects on bone remodeling. Therefore, we hypothesized that ATP signaling is also applied by osteocytes in mechanotransduction. We applied a short fluid pulse on MLO-Y4 osteocyte-like cells during real-time detection of ATP and demonstrated that mechanical stimulation activates the acute release of ATP and that these acute ATP signals are fine-tuned according to the magnitude of loading. ATP release was then challenged by pharmacological inhibitors, which indicated a vesicular release pathway for acute ATP signals. Finally, we showed that osteocytes express functional P2X2 and P2X7 receptors and respond to even low concentrations of nucleotides by increasing intracellular calcium concentration. These results indicate that in osteocytes, vesicular ATP release is an acute mediator of mechanical signals and the magnitude of loading. These and previous results, therefore, implicate purinergic signaling as an early signaling pathway in osteocyte mechanotransduction.
U2 - 10.1016/j.cellsig.2015.08.016
DO - 10.1016/j.cellsig.2015.08.016
M3 - Journal article
C2 - 26327582
VL - 27
SP - 2401
EP - 2409
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 12
ER -
ID: 149041713