Extracellular calcium increases CXCR4 expression on bone marrow-derived cells and enhances pro-angiogenesis therapy

Quiling Wu, Hongwei Shao, D. Darwin Eton, Jiahui Li, Jie Li, Bing Yang, Keith A. Webster, Hong Yu

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3764-3773
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number9 B
DOIs
StatePublished - Sep 2009

Keywords

  • Bone marrow
  • Calcium
  • CXCR4
  • Progenitor cells
  • SDF-1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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