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 language | English (US) |
|---|---|
| Pages (from-to) | 1853-1859 |
| Number of pages | 7 |
| Journal | Journal of Orthopaedic Research |
| Volume | 30 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2012 |
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Keywords
- adult-derived stem cells
- AMD3100
- CXCR4
- fracture
- SDF-1
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
Cite this
Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair. / Toupadakis, Chrisoula A.; Wong, Alice; Genetos, Damian C; Chung, Dai Jung; Murugesh, Deepa; Anderson, Matthew J.; Loots, Gabriela G.; Christiansen, Blaine A; Kapatkin, Amy; Yellowley-genetos, Clare E.
In: Journal of Orthopaedic Research, Vol. 30, No. 11, 11.2012, p. 1853-1859.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Long-term administration of AMD3100, an antagonist of SDF-1/CXCR4 signaling, alters fracture repair
AU - Toupadakis, Chrisoula A.
AU - Wong, Alice
AU - Genetos, Damian C
AU - Chung, Dai Jung
AU - Murugesh, Deepa
AU - Anderson, Matthew J.
AU - Loots, Gabriela G.
AU - Christiansen, Blaine A
AU - Kapatkin, Amy
AU - Yellowley-genetos, Clare E
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - adult-derived stem cells
KW - AMD3100
KW - CXCR4
KW - fracture
KW - SDF-1
UR - http://www.scopus.com/inward/record.url?scp=84867233412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867233412&partnerID=8YFLogxK
U2 - 10.1002/jor.22145
DO - 10.1002/jor.22145
M3 - Article
C2 - 22592891
AN - SCOPUS:84867233412
VL - 30
SP - 1853
EP - 1859
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 11
ER -