title: AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells.
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.
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842, Korea.
authors: Jin Young
authors: JY
authors: Im
authors: Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu 700-721, Korea.
authors: Woo-Kie
authors: WK
authors: Min
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842, Korea.
authors: Min Hee
authors: MH
authors: Park
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842, Korea.
authors: NamOh
authors: N
authors: Kim
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842, Korea.
authors: Jong Kil
authors: JK
authors: Lee
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu 700-842; Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 700-721, Korea.
authors: Hee Kyung
authors: HK
authors: Jin
authors: Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 702-701, Korea.
authors: Je-Yong
authors: JY
authors: Choi
authors: Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu 700-721, Korea.
authors: Shin-Yoon
authors: SY
authors: Kim
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University; Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University; Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu 700-842, Korea.
authors: Jae-sung
authors: JS
authors: Bae
mesh_terms: D000818:Animals; D001596:Benzylamines; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D054377:Chemokine CXCL12 / Q000378:metabolism; D000080027:Cyclams; D004195:Disease Models, Animal; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006571:Heterocyclic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D010024:Osteoporosis / Q000188:drug therapy / Q000628:therapy*; D010052:Ovariectomy; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001596:Benzylamines; D050071:Bone Density Conservation Agents; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor