Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

Hongwei Shao, Qiyuan Xu, Qiuling Wu, Qi Ma, Luis Salgueiro, Jian'An Wang, Darwin Eton, Keith A Webster, Hong Yu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34 + progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses.

Original languageEnglish
Pages (from-to)2046-2056
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number10
DOIs
StatePublished - Oct 1 2011

Fingerprint

Bone Marrow Cells
Blood Vessels
Regeneration
Chemokine CXCL12
Calcium
Muscles
Chemokine Receptors
Hindlimb
Chemokines
Intravenous Injections
Stem Cells
Transplantation

Keywords

  • Aging
  • Angiogenesis
  • Bone marrow cells
  • CXCR4
  • Migration
  • SDF-1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration. / Shao, Hongwei; Xu, Qiyuan; Wu, Qiuling; Ma, Qi; Salgueiro, Luis; Wang, Jian'An; Eton, Darwin; Webster, Keith A; Yu, Hong.

In: Journal of Cellular and Molecular Medicine, Vol. 15, No. 10, 01.10.2011, p. 2046-2056.

Research output: Contribution to journalArticle

Shao, H, Xu, Q, Wu, Q, Ma, Q, Salgueiro, L, Wang, JA, Eton, D, Webster, KA & Yu, H 2011, 'Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration', Journal of Cellular and Molecular Medicine, vol. 15, no. 10, pp. 2046-2056. https://doi.org/10.1111/j.1582-4934.2010.01231.x
Shao, Hongwei ; Xu, Qiyuan ; Wu, Qiuling ; Ma, Qi ; Salgueiro, Luis ; Wang, Jian'An ; Eton, Darwin ; Webster, Keith A ; Yu, Hong. / Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration. In: Journal of Cellular and Molecular Medicine. 2011 ; Vol. 15, No. 10. pp. 2046-2056.
@article{b2217a739f384be398d076fbb6b843a2,
title = "Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration",
abstract = "The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34 + progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses.",
keywords = "Aging, Angiogenesis, Bone marrow cells, CXCR4, Migration, SDF-1",
author = "Hongwei Shao and Qiyuan Xu and Qiuling Wu and Qi Ma and Luis Salgueiro and Jian'An Wang and Darwin Eton and Webster, {Keith A} and Hong Yu",
year = "2011",
month = "10",
day = "1",
doi = "10.1111/j.1582-4934.2010.01231.x",
language = "English",
volume = "15",
pages = "2046--2056",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Defective CXCR4 expression in aged bone marrow cells impairs vascular regeneration

AU - Shao, Hongwei

AU - Xu, Qiyuan

AU - Wu, Qiuling

AU - Ma, Qi

AU - Salgueiro, Luis

AU - Wang, Jian'An

AU - Eton, Darwin

AU - Webster, Keith A

AU - Yu, Hong

PY - 2011/10/1

Y1 - 2011/10/1

N2 - The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34 + progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses.

AB - The chemokine stromal cell-derived factor-1 (SDF-1) plays a critical role in mobilizing precursor cells in the bone marrow and is essential for efficient vascular regeneration and repair. We recently reported that calcium augments the expression of chemokine receptor CXCR4 and enhances the angiogenic potential of bone marrow derived cells (BMCs). Neovascularization is impaired by aging therefore we suggested that aging may cause defects of CXCR4 expression and cellular responses to calcium. Indeed we found that both the basal and calcium-induced surface expression of CXCR4 on BMCs was significantly reduced in 25-month-old mice compared with 2-month-old mice. Reduced Ca-induced CXCR4 expression in BMC from aged mice was associated with defective calcium influx. Diminished CXCR4 surface expression in BMC from aged mice correlated with diminished neovascularization in an ischemic hindlimb model with less accumulation of CD34 + progenitor cells in the ischemic muscle with or without local overexpression of SDF-1. Intravenous injection of BMCs from old mice homed less efficiently to ischemic muscle and stimulated significantly less neovascularization compared with the BMCs from young mice. Transplantation of old BMCs into young mice did not reconstitute CXCR4 functions suggesting that the defects were not reversible by changing the environment. We conclude that defects of basal and calcium-regulated functions of the CXCR4/SDF-1 axis in BMCs contribute significantly to the age-related loss of vasculogenic responses.

KW - Aging

KW - Angiogenesis

KW - Bone marrow cells

KW - CXCR4

KW - Migration

KW - SDF-1

UR - http://www.scopus.com/inward/record.url?scp=80053267946&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053267946&partnerID=8YFLogxK

U2 - 10.1111/j.1582-4934.2010.01231.x

DO - 10.1111/j.1582-4934.2010.01231.x

M3 - Article

C2 - 21143386

AN - SCOPUS:80053267946

VL - 15

SP - 2046

EP - 2056

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 10

ER -