Abstract
Mechanical loading is a key anabolic regulator of bone mass. Stromal cell-derived factor-1 (SDF-1) is a stem cell homing factor that is important in hematopoiesis, angiogenesis, and fracture healing, though its involvement in skeletal mechanoadaptation is virtually unknown. The objective of this study was to characterize skeletal expression patterns of SDF-1 and CXCR4, the receptor for SDF-1, and to determine the role of SDF-1 signaling in load-induced periosteal bone formation. Sixteen-week-old C57BL/6 mice were treated with PBS or AMD3100, an antagonist against CXCR4, and exposed to in vivo ulnar loading (2.8 N peak-to-peak, 2 Hz, 120 cycles). SDF-1 was expressed in cortical and trabecular osteocytes and marrow cells, and CXCR4 was primarily expressed in marrow cells. SDF-1 and CXCR4 expression was enhanced in response to mechanical stimulation. The CXCR4 receptor antagonist AMD3100 significantly attenuated load-induced bone formation and led to smaller adaptive changes in cortical geometric properties as determined by histomorphometric analysis. Our data suggest that SDF-1/CXCR4 signaling plays a critical role in skeletal mechanoadaptation, and may represent a unique therapeutic target for prevention and treatment of age-related and disuse bone loss.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1828-1838 |
| Number of pages | 11 |
| Journal | Journal of Orthopaedic Research |
| Volume | 31 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2013 |
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Keywords
- CXCR4
- mechanoadaptation
- osteogenesis
- SDF-1
- ulnar loading
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
Cite this
CXCR4 antagonism attenuates load-induced periosteal bone formation in mice. / Leucht, Philipp; Temiyasathit, Sara; Russell, Ashley; Arguello, Juan F.; Jacobs, Christopher R.; Helms, Jill A.; Castillo, Alesha.
In: Journal of Orthopaedic Research, Vol. 31, No. 11, 11.2013, p. 1828-1838.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CXCR4 antagonism attenuates load-induced periosteal bone formation in mice
AU - Leucht, Philipp
AU - Temiyasathit, Sara
AU - Russell, Ashley
AU - Arguello, Juan F.
AU - Jacobs, Christopher R.
AU - Helms, Jill A.
AU - Castillo, Alesha
PY - 2013/11
Y1 - 2013/11
N2 - Mechanical loading is a key anabolic regulator of bone mass. Stromal cell-derived factor-1 (SDF-1) is a stem cell homing factor that is important in hematopoiesis, angiogenesis, and fracture healing, though its involvement in skeletal mechanoadaptation is virtually unknown. The objective of this study was to characterize skeletal expression patterns of SDF-1 and CXCR4, the receptor for SDF-1, and to determine the role of SDF-1 signaling in load-induced periosteal bone formation. Sixteen-week-old C57BL/6 mice were treated with PBS or AMD3100, an antagonist against CXCR4, and exposed to in vivo ulnar loading (2.8 N peak-to-peak, 2 Hz, 120 cycles). SDF-1 was expressed in cortical and trabecular osteocytes and marrow cells, and CXCR4 was primarily expressed in marrow cells. SDF-1 and CXCR4 expression was enhanced in response to mechanical stimulation. The CXCR4 receptor antagonist AMD3100 significantly attenuated load-induced bone formation and led to smaller adaptive changes in cortical geometric properties as determined by histomorphometric analysis. Our data suggest that SDF-1/CXCR4 signaling plays a critical role in skeletal mechanoadaptation, and may represent a unique therapeutic target for prevention and treatment of age-related and disuse bone loss.
AB - Mechanical loading is a key anabolic regulator of bone mass. Stromal cell-derived factor-1 (SDF-1) is a stem cell homing factor that is important in hematopoiesis, angiogenesis, and fracture healing, though its involvement in skeletal mechanoadaptation is virtually unknown. The objective of this study was to characterize skeletal expression patterns of SDF-1 and CXCR4, the receptor for SDF-1, and to determine the role of SDF-1 signaling in load-induced periosteal bone formation. Sixteen-week-old C57BL/6 mice were treated with PBS or AMD3100, an antagonist against CXCR4, and exposed to in vivo ulnar loading (2.8 N peak-to-peak, 2 Hz, 120 cycles). SDF-1 was expressed in cortical and trabecular osteocytes and marrow cells, and CXCR4 was primarily expressed in marrow cells. SDF-1 and CXCR4 expression was enhanced in response to mechanical stimulation. The CXCR4 receptor antagonist AMD3100 significantly attenuated load-induced bone formation and led to smaller adaptive changes in cortical geometric properties as determined by histomorphometric analysis. Our data suggest that SDF-1/CXCR4 signaling plays a critical role in skeletal mechanoadaptation, and may represent a unique therapeutic target for prevention and treatment of age-related and disuse bone loss.
KW - CXCR4
KW - mechanoadaptation
KW - osteogenesis
KW - SDF-1
KW - ulnar loading
UR - http://www.scopus.com/inward/record.url?scp=84884906809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884906809&partnerID=8YFLogxK
U2 - 10.1002/jor.22440
DO - 10.1002/jor.22440
M3 - Article
C2 - 23881789
AN - SCOPUS:84884906809
VL - 31
SP - 1828
EP - 1838
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
SN - 0736-0266
IS - 11
ER -