P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts

TY - JOUR

T1 - P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts

AU - Agrawal, Ankita

AU - Henriksen, Zanne

AU - Syberg, Susanne

AU - Petersen, Solveig

AU - Aslan, Derya

AU - Solgaard, Marie

AU - Nissen, Nis

AU - Larsen, Tommy Korsgaard

AU - Schwarz, Peter

AU - Steinberg, Thomas H

AU - Jørgensen, Niklas Rye

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling. We report that osteoblasts derived from human trabecular explants express a functional P2X7R capable of agonist-induced increase in intracellular calcium concentration and a positive permeability to fluorescent dyes. These osteoblasts are fully differentiated cells with alkaline phosphatase activity and the ability to form mineralized nodules. We show that the transcriptional regulation of osteoblastic markers can be modulated by P2X7R activity or blockade thereby influencing the differentiation, proliferation and bone matrix formation by these primary human osteoblasts. Finally, we demonstrate that the P2X7R is involved in propagation of mechanically-induced intercellular signaling in addition to the known mechanisms involving calcium signaling via P2Y2 receptors and gap junction.

AB - The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells however; its role in human primary osteoblasts has not yet been reported. The aim of this study was to assess the expression of the P2X7R in bone marrow-derived stromal cells and in primary human trabecular osteoblasts and to determine the function in bone formation and cell signaling. We report that osteoblasts derived from human trabecular explants express a functional P2X7R capable of agonist-induced increase in intracellular calcium concentration and a positive permeability to fluorescent dyes. These osteoblasts are fully differentiated cells with alkaline phosphatase activity and the ability to form mineralized nodules. We show that the transcriptional regulation of osteoblastic markers can be modulated by P2X7R activity or blockade thereby influencing the differentiation, proliferation and bone matrix formation by these primary human osteoblasts. Finally, we demonstrate that the P2X7R is involved in propagation of mechanically-induced intercellular signaling in addition to the known mechanisms involving calcium signaling via P2Y2 receptors and gap junction.

KW - Journal Article

U2 - 10.1016/j.bone.2016.11.011

DO - 10.1016/j.bone.2016.11.011

M3 - Journal article

C2 - 27856358

SN - 8756-3282

VL - 95

SP - 91

EP - 101

JO - Bone

JF - Bone

ER -