A pivotal role of bone remodeling in granulocyte colony stimulating factor induced hematopoietic stem/progenitor cells mobilization |
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| Authors: | Sidan Li Qiongli Zhai Dehui Zou Hengxing Meng Zhenqing Xie Changhong Li Yafei Wang Junyuan Qi Tao Cheng Lugui Qiu |
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| Affiliation: | 1. State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College, Tianjin, China;2. Hematological Center, Beijing Children's Hospital, Capital Medical University, Beijing, China;3. Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China;4. Tianjin Cord Blood Bank of National Research Center for Stem Cell Engineering and Technology, Tianjin, China;5. Department of Hematology, Tianjin Medical University Cancer Hospital, Tianjin, China |
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| Abstract: | The majority of hematopoietic stem/progenitor cells (HSPCs) reside in bone marrow (BM) surrounded by a specialized environment, which governs HSPC function. Here we investigated the potential role of bone remodeling cells (osteoblasts and osteoclasts) in homeostasis and stress‐induced HSPC mobilization. Peripheral blood (PB) and BM in steady/mobilized state were collected from healthy donors undergoing allogeneic transplantation and from mice treated with granulocyte colony stimulating factor (G‐CSF), parathyroid hormone (PTH), or receptor activator of nuclear factor kappa‐B ligand (RANKL). The number and the functional markers of osteoblasts and osteoclasts were checked by a series of experiments. Our data showed that the number of CD45?Ter119? osteopontin (OPN)+ osteoblasts was significantly reduced from 4,085 ± 135 cells/femur on Day 0 to 1,032 ± 55 cells/femur on Day 5 in mice (P = 0.02) and from 21.38 ± 0.66 on Day 0 to 14.78 ± 0.65 on Day 5 in healthy donors (P < 0.01). Decrease of osteoblast number leads to reduced level of HSPC mobilization regulators stromal cell‐derived factor‐1 (SDF‐1), stem cell factor (SCF), and OPN. The osteoclast number at bone surface (OC.N/B.s) was significantly increased from 1.53 ± 0.12 on Day 0 to 4.42 ± 0.46 on Day 5 (P < 0.01) in G‐CSF‐treated mice and from 0.88 ± 0.20 on Day 0 to 3.24 ± 0.31 on Day 5 (P < 0.01) in human. Serum TRACP‐5b level showed a biphasic trend during G‐CSF treatment. The ratio of osteoblasts number per bone surface (OB.N/B.s) to OC.N/B.s was changed after adding PTH plus RANKL during G‐CSF treatment. In conclusion, short term G‐CSF treatment leads to reduction of osteoblasts and stimulation of osteoclasts, and interrupting bone remodeling balance may contribute to HSPC mobilization. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. |
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