Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair

Chrisoula A. Toupadakis, Alice Wong, Damian C Genetos, Dai Jung Chung, Deepa Murugesh, Matthew J. Anderson, Gabriela G. Loots, Blaine A Christiansen, Amy Kapatkin, Clare E Yellowley-genetos

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Fracture healing involves rapid stem and progenitor cell migration, homing, and differentiation. SDF-1 (CXCL12) is considered a master regulator of CXCR4-positive stem and progenitor cell trafficking to sites of ischemic (hypoxic) injury and regulates their subsequent differentiation into mature reparative cells. In this study, we investigated the role of SDF-1/CXCR4 signaling in fracture healing where vascular disruption results in hypoxia and SDF-1 expression. Mice were injected with AMD3100, a CXCR4 antagonist, or vehicle twice daily until euthanasia with the intent to impair stem cell homing to the fracture site and/or their differentiation. Fracture healing was evaluated using micro-computed tomography, histology, quantitative PCR, and mechanical testing. AMD3100 administration resulted in a significantly reduced hyaline cartilage volume (day 14), callus volume (day 42) and mineralized bone volume (day 42) and reduced expression of genes associated with endochondral ossification including collagen Type 1 alpha 1, collagen Type 2 alpha 1, vascular endothelial growth factor, Annexin A5, nitric oxide synthase 2, and mechanistic target of rapamycin. Our data suggest that the SDF-1/CXCR4 signaling plays a central role in bone healing possibly by regulating the recruitment and/or differentiation of stem and progenitor cells.

Original languageEnglish (US)
Pages (from-to)1853-1859
Number of pages7
JournalJournal of Orthopaedic Research
Volume30
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • adult-derived stem cells
  • AMD3100
  • CXCR4
  • fracture
  • SDF-1

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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