CXCR4 antagonism attenuates load-induced periosteal bone formation in mice

Philipp Leucht, Sara Temiyasathit, Ashley Russell, Juan F. Arguello, Christopher R. Jacobs, Jill A. Helms, Alesha Castillo

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1828-1838
Number of pages11
JournalJournal of Orthopaedic Research
Volume31
Issue number11
DOIs
StatePublished - Nov 2013

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Chemokine CXCL12
Osteogenesis
CXCR4 Receptors
Bone Marrow
Osteocytes
Fracture Healing
Stem Cell Factor
Hematopoiesis
Inbred C57BL Mouse
Osteoporosis
Bone and Bones

Keywords

  • CXCR4
  • mechanoadaptation
  • osteogenesis
  • SDF-1
  • ulnar loading

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Leucht, P., Temiyasathit, S., Russell, A., Arguello, J. F., Jacobs, C. R., Helms, J. A., & Castillo, A. (2013). CXCR4 antagonism attenuates load-induced periosteal bone formation in mice. Journal of Orthopaedic Research, 31(11), 1828-1838. https://doi.org/10.1002/jor.22440

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 journalArticle

Leucht, P, Temiyasathit, S, Russell, A, Arguello, JF, Jacobs, CR, Helms, JA & Castillo, A 2013, 'CXCR4 antagonism attenuates load-induced periosteal bone formation in mice', Journal of Orthopaedic Research, vol. 31, no. 11, pp. 1828-1838. https://doi.org/10.1002/jor.22440
Leucht P, Temiyasathit S, Russell A, Arguello JF, Jacobs CR, Helms JA et al. CXCR4 antagonism attenuates load-induced periosteal bone formation in mice. Journal of Orthopaedic Research. 2013 Nov;31(11):1828-1838. https://doi.org/10.1002/jor.22440
Leucht, Philipp ; Temiyasathit, Sara ; Russell, Ashley ; Arguello, Juan F. ; Jacobs, Christopher R. ; Helms, Jill A. ; Castillo, Alesha. / CXCR4 antagonism attenuates load-induced periosteal bone formation in mice. In: Journal of Orthopaedic Research. 2013 ; Vol. 31, No. 11. pp. 1828-1838.
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