title: A pivotal role of bone remodeling in granulocyte colony stimulating factor induced hematopoietic stem/progenitor cells mobilization.
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.
authors.affiliation: 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.
authors.forename: Sidan
authors.initials: S
authors.lastname: Li
authors.forename: Qiongli
authors.initials: Q
authors.lastname: Zhai
authors.forename: Dehui
authors.initials: D
authors.lastname: Zou
authors.forename: Hengxing
authors.initials: H
authors.lastname: Meng
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Xie
authors.forename: Changhong
authors.initials: C
authors.lastname: Li
authors.forename: Yafei
authors.initials: Y
authors.lastname: Wang
authors.forename: Junyuan
authors.initials: J
authors.lastname: Qi
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D002454:Cell Differentiation; D054377:Chemokine CXCL12 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D010281:Parathyroid Hormone / Q000008:administration & dosage; D053245:RANK Ligand / Q000008:administration & dosage; D014184:Transplantation, Homologous
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D010281:Parathyroid Hormone; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D053495:Osteopontin; D016179:Granulocyte Colony-Stimulating Factor