Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors.
Signaling between osteoblasts and osteoclasts is important in bone homeostasis. We previously showed that human osteoblasts propagate intercellular calcium signals via two mechanisms: autocrine activation of P2Y receptors, and gap junctional communication. In the current work we identified mechanically induced intercellular calcium signaling between osteoblasts and osteoclasts and among osteoclasts. Intercellular calcium responses in osteoclasts required P2 receptor activation but not gap junctional communication. Pharmacological studies and reverse transcriptase-PCR amplification demonstrated that human osteoclasts expressed functional P2Y1 receptors, but, unexpectedly, desensitization of P2Y1 did not block calcium signaling to osteoclasts. We also found that osteoclasts expressed functional P2X7 receptors and showed that pharmacological inhibition of these receptors blocked calcium signaling to osteoclasts. Thus these studies show that calcium signaling between osteoblasts and osteoclasts occurs via activation of P2 receptors, but that different families of P2 receptors are required for calcium signaling in these two cell types. Intercellular calcium signaling among bone cells is therefore amenable to pharmacological manipulation that will specifically affect only bone-forming or bone-resorbing cells. P2 receptors may be important drug targets for the modulation of bone turnover.
Jørgensen
Niklas R
NR
Osteoporosis Research Clinic, Dept. 545, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, Hvidovre DK-2650, Denmark. niklas@dadlnet.dk
Henriksen
Zanne
Z
Sørensen
Ole H
OH
Eriksen
Erik F
EF
Civitelli
Roberto
R
Steinberg
Thomas H
TH
D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism*; D011485:Protein Binding; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D002352:Carrier Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; C546468:P2RX7 protein, human; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D016173:Macrophage Colony-Stimulating Factor; D002118:Calcium