AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells
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Inhibition of an increase of osteoclasts has become the mostimportant treatment for osteoporosis. The CXCR4 antagonist,AMD3100, plays an important role in the mobilization ofosteoclast precursors within bone marrow (BM). However, theactual therapeutic impact of AMD3100 in osteoporosis has notyet been ascertained. Here we demonstrate the therapeuticeffect of AMD3100 in the treatment of ovariectomy-inducedosteoporosis in mice. We found that treatment with AMD3100resulted in direct induction of release of SDF-1 from BM toblood and mobilization of hematopoietic stem/progenitor cells(HSPCs) in an osteoporosis model. AMD3100 prevented bonedensity loss after ovariectomy by mobilization of HSPCs,suggesting a therapeutic strategy to reduce the number ofosteoclasts on bone surfaces. These findings support thehypothesis that treatment with AMD3100 can result in efficientmobilization of HSPCs into blood through direct blockade ofthe SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis.
Abstract
Inhibition of an increase of osteoclasts has become the mostimportant treatment for osteoporosis. The CXCR4 antagonist,AMD3100, plays an important role in the mobilization ofosteoclast precursors within bone marrow (BM). However, theactual therapeutic impact of AMD3100 in osteoporosis has notyet been ascertained. Here we demonstrate the therapeuticeffect of AMD3100 in the treatment of ovariectomy-inducedosteoporosis in mice. We found that treatment with AMD3100resulted in direct induction of release of SDF-1 from BM toblood and mobilization of hematopoietic stem/progenitor cells(HSPCs) in an osteoporosis model. AMD3100 prevented bonedensity loss after ovariectomy by mobilization of HSPCs,suggesting a therapeutic strategy to reduce the number ofosteoclasts on bone surfaces. These findings support thehypothesis that treatment with AMD3100 can result in efficientmobilization of HSPCs into blood through direct blockade ofthe SDF-1/CXCR4 interaction in BM and can be considered as a potential new therapeutic intervention for osteoporosis.
참고문헌 (19)
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