Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation

Tissue Eng Part A. 2011 Feb;17(3-4):523-30. doi: 10.1089/ten.tea.2010.0168. Epub 2010 Nov 2.

Abstract

The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Development / physiology*
  • Bone Morphogenetic Protein 2 / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Chemokine CXCL12 / metabolism*
  • Chemokines / metabolism*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / physiology*
  • Osteogenesis / physiology*
  • Rats
  • Rats, Nude

Substances

  • Bone Morphogenetic Protein 2
  • Chemokine CXCL12
  • Chemokines