Extracellular calcium modulates in vitro bone marrow-derived Flk-1+ CD34+ progenitor cell chemotaxis and differentiation through a calcium-sensing receptor.
Angiogenesis is a complex process regulated by many cell types and a large variety of biochemical signals such as growth factors, transcription factors, oxygen and nutrient diffusion among others. In the present study, we found out that Flk-1(+) CD34(+) progenitor cells (bone marrow resident cells with an important role in angiogenesis) were responsive to changes in extracellular calcium concentration through a membrane bound, G-protein-coupled receptor sensitive to calcium ions related to the calcium-sensing receptor (CaSR). Calcium was able to induce progenitor cell migration in Boyden chamber experiments and tubulogenesis in Matrigel assays. Addition of anti-CaSR antibodies completely blocked the effect, while CaSR agonist Mg(2+) produced a similar response to that of calcium. Real time RT-PCR for a wide array of angiogenesis-related genes showed increased expression of endothelial markers and signaling pathways involved in angiogenesis. These results suggest calcium could be a physiological modulator of the bone marrow progenitor cell-mediated angiogenic response.
Aguirre
A
A
Institute for Bioengineering of Catalonia (IBEC), 08028 Barcelona, Spain.
González
A
A
Planell
J A
JA
Engel
E
E
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D018952:Antigens, CD34; D044169:Receptors, Calcium-Sensing; D040301:Vascular Endothelial Growth Factor Receptor-2; D008274:Magnesium; D002118:Calcium