Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.
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.
Atlanta Veteran Affairs Medical Center and Department of Orthopaedics, Emory University School of Medicine, Atlanta, Georgia, USA.
Kosaku
K
Higashino
Manjula
M
Viggeswarapu
Maggie
M
Bargouti
Hui
H
Liu
Louisa
L
Titus
Scott D
SD
Boden
D000818:Animals; D001846:Bone Development / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D011923:Rats, Nude
D055396:Bone Morphogenetic Protein 2; D054377:Chemokine CXCL12; D018925:Chemokines