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

Craig L Semerad, Matthew J. Christopher, Fulu Liu, Brenton Short, Paul J. Simmons, Ingrid Winkler, Jean Pierre Levesque, Jean Chappel, F. Patrick Ross, Daniel C. Link

Research output: Contribution to journalArticle

353 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3020-3027
Number of pages8
JournalBlood
Volume106
Issue number9
DOIs
StatePublished - Nov 1 2005

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Osteoblasts
Granulocyte Colony-Stimulating Factor
Hematopoietic Stem Cells
Bone
Bone Marrow
Messenger RNA
Granulocyte Colony-Stimulating Factor Receptors
Chemokine CXCL12
Proteins
Osteocalcin
Endothelial cells
Sorting
Transgenic Mice
Endothelial Cells
Cells
Ligands
Mutation
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Semerad, C. L., Christopher, M. J., Liu, F., Short, B., Simmons, P. J., Winkler, I., ... Link, D. C. (2005). G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood, 106(9), 3020-3027. https://doi.org/10.1182/blood-2004-01-0272

G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. / Semerad, Craig L; Christopher, Matthew J.; Liu, Fulu; Short, Brenton; Simmons, Paul J.; Winkler, Ingrid; Levesque, Jean Pierre; Chappel, Jean; Ross, F. Patrick; Link, Daniel C.

In: Blood, Vol. 106, No. 9, 01.11.2005, p. 3020-3027.

Research output: Contribution to journalArticle

Semerad, CL, Christopher, MJ, Liu, F, Short, B, Simmons, PJ, Winkler, I, Levesque, JP, Chappel, J, Ross, FP & Link, DC 2005, 'G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow', Blood, vol. 106, no. 9, pp. 3020-3027. https://doi.org/10.1182/blood-2004-01-0272
Semerad, Craig L ; Christopher, Matthew J. ; Liu, Fulu ; Short, Brenton ; Simmons, Paul J. ; Winkler, Ingrid ; Levesque, Jean Pierre ; Chappel, Jean ; Ross, F. Patrick ; Link, Daniel C. / G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. In: Blood. 2005 ; Vol. 106, No. 9. pp. 3020-3027.
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