Key result
G-CSF increases peripheral LSK cells ~15-fold over controls while reducing bone marrow Ang1 expression.
Why the study?
Does G-CSF administration alter Ang1 expression and osteoblast numbers during hematopoietic stem/progenitor cell mobilization in mice?
Does G-CSF administration alter Ang1 expression and osteoblast numbers during hematopoietic stem/progenitor cell mobilization in mice?
Absolute Event Rate: 0.61% vs 0.04%
p-value: p=0.011
G-CSF-induced hematopoietic stem/progenitor cell mobilization involves the reduction of bone marrow osteoblasts and subsequent decrease in Ang1 expression.
Osteoblast retraction reduces Ang1 to aid G-CSF mobilization in mice; leaves open relevance to human HSPC mobilization.
OBJECTIVE: To investigate the changes and mechanism of angiopoietin1 (Ang1) in murine bone marrow during G-CSF induced mobilization of hematopoietic stem/progenitor cell. METHODS: The proportion of Lin-Sca1⁺cKit⁺ (LSK) cells in peripheral blood of C57BL/6 mice before and after G-CSF mobilization was detected by flow cytometry. Expression changes of Ang1 and osteocalcin (OCN) during HSC mobilization were determined by immunohistochemistry, enzyme linked immunosorbent assay (ELISA) and real-time fluorescence quantitative PCR. The number of osteoblasts in the bone marrow was counted under the microscope. RESULTS: After treated with G-CSF, the proportion of LSK cells in peripheral blood significantly increased from the controls (0.04 ± 0.01)% to (0.61 ± 0.05)% at day 5 (P<0.05). Before G-CSF mobilization, the endosteum cells expressed higher level of OCN and Ang1 than that of bone marrow nucleated cells. The mRNA expression level of OCN was significantly reduced from 28.64 ± 8.61 in the controls to 12.55 ± 7.06 on day 3 and 4.75 ± 1.62 on day 5, and the expression level of Ang1 also declined from 2.84 ± 0.95 in the controls to 0.93 ± 0.30 on day 3 and to 0.92 ± 0.22 on day 5 after G-CSF mobilization. The number of endosteum osteoblasts was significantly decreased after mobilization (P<0.05). The Ang1 expression was decreased in the BM after mobilization. The serum OCN was significantly reduced from (24.11 ± 3.17) ng/ml in the controls to (9.96 ± 2.16) ng/ml on day 3 and (8.43 ± 2.62) ng/ml on day 5, and the Ang1 also declined from (2.24 ± 0.52) ng/ml in the controls to (1.21±0.38) ng/ml on day 3 and (0.90±0.24) ng/ml on day 5. CONCLUSION: In G-CSFinduced HSPC mobilization, the bone marrow osteoblasts retraction causes reduction of Ang1, and the reduction of Ang1 may contribute to HSPC mobilization.
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Li et al. (2015) studied Hematopoietic stem/progenitor cell mobilization (n=15). G-CSF vs. Saline was evaluated on Proportion of Lin-Sca1+cKit+ (LSK) cells in peripheral blood at day 5 (p=0.011). G-CSF treatment significantly increased the proportion of LSK cells in peripheral blood to 0.61% at day 5 compared to 0.04% in controls, while decreasing bone marrow Ang1 expression.
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