G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow

Semerad, CL, Christopher, MJ, Liu, FL, Short, B, Simmons, PJ, Winkler, I, Levesque, JP, Chappel, J, Ross, FP and Link, DC (2005) G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood, 106 9: 3020-3027. doi:10.1182/blood-2004-01-0272

Author Semerad, CL
Christopher, MJ
Liu, FL
Short, B
Simmons, PJ
Winkler, I
Levesque, JP
Chappel, J
Ross, FP
Link, DC
Title G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2005-01-01
Year available 2005
Sub-type Article (original research)
DOI 10.1182/blood-2004-01-0272
Open Access Status Not yet assessed
Volume 106
Issue 9
Start page 3020
End page 3027
Total pages 8
Place of publication WASHINGTON
Language eng
Subject 2720 Hematology
Abstract Accumulating evidence indicates that interaction of stromal cell-derived factor 1 (SDF-1/CXCL12 [CXC motif, ligand 12]) with its cognate receptor, CXCR4 (CXC motif, receptor 4), generates signals that regulate hematopoietic progenitor cell (HPC) trafficking in the bone marrow. During granulocyte colony-stimulating factor (G-CSF)-induced HPC mobilization, CXCL12 protein expression in the bone marrow decreases. Herein, we show that in a series of transgenic mice carrying targeted mutations of their G-CSF receptor and displaying markedly different G-CSF-induced HPC mobilization responses, the decrease in bone marrow CXCL12 protein expression closely correlates with the degree of HPC mobilization. G-CSF treatment induced a decrease in bone marrow CXCL12 mRNA that closely mirrored the fall in CXCL12 protein. Cell sorting experiments showed that osteoblasts and to a lesser degree endothelial cells are the major sources of CXCL12 production in the bone marrow. Interestingly, osteoblast activity, as measured by histomorphometry and osteocalcin expression, is strongly down-regulated during G-CSF treatment. However, the G-CSF receptor is not expressed on osteoblasts; accordingly, G-CSF had no direct effect on osteoblast function. Collectively, these data suggest a model in which G-CSF, through an indirect mechanism, potently inhibits osteoblast activity resulting in decreased CXCL12 expression in the bone marrow. The consequent attenuation of CXCR4 signaling ultimately leads to HPC mobilization.
Keyword Hematology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID T32 HL 07088-23
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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