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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells

  • Im, Jin Young (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Min, Woo-Kie (Department of Orthopaedic Surgery, Kyungpook National University Hospital) ;
  • Park, Min Hee (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Kim, NamOh (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Lee, Jong Kil (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Jin, Hee Kyung (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Choi, Je-Yong (Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University) ;
  • Kim, Shin-Yoon (Department of Orthopaedic Surgery, Kyungpook National University Hospital) ;
  • Bae, Jae-Sung (Stem Cell Neuroplasticity Research Group, Kyungpook National University)
  • Received : 2013.07.10
  • Accepted : 2013.11.19
  • Published : 2014.08.31
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Abstract

Inhibition of an increase of osteoclasts has become the most important treatment for osteoporosis. The CXCR4 antagonist, AMD3100, plays an important role in the mobilization of osteoclast precursors within bone marrow (BM). However, the actual therapeutic impact of AMD3100 in osteoporosis has not yet been ascertained. Here we demonstrate the therapeutic effect of AMD3100 in the treatment of ovariectomy-induced osteoporosis in mice. We found that treatment with AMD3100 resulted in direct induction of release of SDF-1 from BM to blood and mobilization of hematopoietic stem/progenitor cells (HSPCs) in an osteoporosis model. AMD3100 prevented bone density loss after ovariectomy by mobilization of HSPCs, suggesting a therapeutic strategy to reduce the number of osteoclasts on bone surfaces. These findings support the hypothesis that treatment with AMD3100 can result in efficient mobilization of HSPCs into blood through direct blockade of the SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis.

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References

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