Low-dose bone morphogenetic protein-2/stromal cell-derived factor-1ß cotherapy induces bone regeneration in critical-size rat calvarial defects.
Tissue Eng Part A
; 20(9-10): 1444-53, 2014 May.
Article
in En
| MEDLINE
| ID: mdl-24341891
ABSTRACT
Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1ß, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1ß enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1ß to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1ß potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1ß potentiates suboptimal BMP-2 (0.5 µg) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0 µg) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1ß provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skull Fractures
/
Bone Regeneration
/
Drug Implants
/
Chemokine CXCL12
/
Bone Morphogenetic Protein 2
Type of study:
Prognostic_studies
/
Qualitative_research
Limits:
Animals
Language:
En
Journal:
Tissue Eng Part A
Journal subject:
BIOTECNOLOGIA
/
HISTOLOGIA
Year:
2014
Type:
Article
Affiliation country:
Georgia