PMID- 19220581 OWN - NLM STAT- MEDLINE DCOM- 20111223 LR - 20211203 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 13 IP - 9B DP - 2009 Sep TI - Extracellular calcium increases CXCR4 expression on bone marrow-derived cells and enhances pro-angiogenesis therapy. PG - 3764-73 LID - 10.1111/j.1582-4934.2009.00691.x [doi] AB - Cell surface receptors play major roles in the mobilization and homing of progenitor cells from the bone marrow to peripheral tissues. CXCR4 is an important receptor that regulates homing of leucocytes and endothelial progenitors in response to the chemokine stromal cell-derived factor-1 (SDF-1). Ionic calcium is also known to regulate chemotaxis of selective bone marrow cells (BMCs) through the calcium-sensing receptor, CaR. Here we show that calcium regulates CXCR4 expression and BMC responses to SDF-1. CaCl(2) treatment of BMC induced a time- and dose-dependent increase in both the transcription and cell surface expression of CXCR4. BMC subpopulations expressing VEGFR2(+), CD34(+) and cKit(+)/Sca-1(+) were especially sensitive to calcium. The effects were blocked by calcium influx inhibitors, anti-CaR antibody and the protein synthesis inhibitor cycloheximide, but not by the CXCR4 antagonist AMD3100. Calcium treatment also enhanced SDF-1-mediated CXCR4 internalization. These changes were reflected in significantly improved chemotaxis by SDF-1, which was abolished by AMD3100 and by antibody against CXCR4. Calcium pre-treatment improved homing of CD34(+) BMCs to ischemic muscle in vivo, and enhanced revascularization in ischemic mouse hindlimbs. Our results identify calcium as a positive regulator of CXCR4 expression that promotes stem cell mobilization, homing and therapy. FAU - Wu, Quiling AU - Wu Q AD - Vascular Biology Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, USA. FAU - Shao, Hongwei AU - Shao H FAU - Darwin, Eton D AU - Darwin ED FAU - Li, Jiahui AU - Li J FAU - Li, Jie AU - Li J FAU - Yang, Bing AU - Yang B FAU - Webster, Keith A AU - Webster KA FAU - Yu, Hong AU - Yu H LA - eng GR - R01 HL072924/HL/NHLBI NIH HHS/United States GR - R01 HL072924-04/HL/NHLBI NIH HHS/United States GR - R01 HL092499/HL/NHLBI NIH HHS/United States GR - R01 HL092499-01A1/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20090209 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (Benzylamines) RN - 0 (Cyclams) RN - 0 (Heterocyclic Compounds) RN - 0 (Receptors, CXCR4) RN - 0 (Receptors, Calcium-Sensing) RN - 98600C0908 (Cycloheximide) RN - S915P5499N (plerixafor) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Benzylamines MH - Bone Marrow Cells/*metabolism MH - Calcium/*metabolism MH - Chemotaxis MH - Cyclams MH - Cycloheximide/pharmacology MH - Dose-Response Relationship, Drug MH - *Gene Expression Regulation MH - Hematopoietic Stem Cell Mobilization MH - Heterocyclic Compounds/pharmacology MH - Mice MH - Mice, Inbred C57BL MH - *Neovascularization, Physiologic MH - Receptors, CXCR4/*biosynthesis MH - Receptors, Calcium-Sensing/metabolism MH - Stem Cells/cytology PMC - PMC3124762 MID - NIHMS305539 EDAT- 2009/02/18 09:00 MHDA- 2011/12/24 06:00 PMCR- 2009/09/01 CRDT- 2009/02/18 09:00 PHST- 2009/02/18 09:00 [entrez] PHST- 2009/02/18 09:00 [pubmed] PHST- 2011/12/24 06:00 [medline] PHST- 2009/09/01 00:00 [pmc-release] AID - JCMM691 [pii] AID - 10.1111/j.1582-4934.2009.00691.x [doi] PST - ppublish SO - J Cell Mol Med. 2009 Sep;13(9B):3764-73. doi: 10.1111/j.1582-4934.2009.00691.x. Epub 2009 Feb 9.