Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Blood, 2005-11, Vol.106 (9), p.3020-3027

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2005

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.