TY - GEN
T1 - Cooperation of β2- and β3-adrenergic receptors in hematopoietic progenitor cell mobilization
AU - Méndez-Ferrer, Simón
AU - Battista, Michela
AU - Frenette, Paul S.
PY - 2010/3
Y1 - 2010/3
N2 - CXCL12/SDF-1 dynamically regulates hematopoietic stem cell (HSC) attraction in the bone marrow (BM). Circadian regulation of bone formation and HSC traffic is relayed in bone and BM by β-adrenergic receptors (β-AR) expressed on HSCs, osteoblasts, and mesenchymal stem/progenitor cells. Circadian HSC release from the BM follows rhythmic secretion of norepinephrine from nerve terminals, β3-AR activation, and Cxcl12 downregulation, possibly from reduced Sp1 nuclear content. Here, we show that β-AR stimulation in stromal cells causes Sp1 degradation, partially mediated by the 26S proteasome. Inverted trends of circulating hematopoietic progenitors and BM Cxcl12 mRNA levels change acutely after light onset, shown to induce sympathetic efferent activity. In BM stromal cells, activation of β3-AR downregulates Cxcl12, whereas β2-AR stimulation induces clock gene expression. Double deficiency in β2- and β3-ARs compromises enforced mobilization. Therefore, β2- and β3-ARs have specific roles in stromal cells and cooperate during progenitor mobilization.
AB - CXCL12/SDF-1 dynamically regulates hematopoietic stem cell (HSC) attraction in the bone marrow (BM). Circadian regulation of bone formation and HSC traffic is relayed in bone and BM by β-adrenergic receptors (β-AR) expressed on HSCs, osteoblasts, and mesenchymal stem/progenitor cells. Circadian HSC release from the BM follows rhythmic secretion of norepinephrine from nerve terminals, β3-AR activation, and Cxcl12 downregulation, possibly from reduced Sp1 nuclear content. Here, we show that β-AR stimulation in stromal cells causes Sp1 degradation, partially mediated by the 26S proteasome. Inverted trends of circulating hematopoietic progenitors and BM Cxcl12 mRNA levels change acutely after light onset, shown to induce sympathetic efferent activity. In BM stromal cells, activation of β3-AR downregulates Cxcl12, whereas β2-AR stimulation induces clock gene expression. Double deficiency in β2- and β3-ARs compromises enforced mobilization. Therefore, β2- and β3-ARs have specific roles in stromal cells and cooperate during progenitor mobilization.
KW - Bone marrow stromal cells
KW - CXCL12/SDF-1
KW - Circadian
KW - Clock
KW - Hematopoietic progenitor mobilization
KW - β-adrenergic receptors
UR - http://www.scopus.com/inward/record.url?scp=77950647414&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77950647414&partnerID=8YFLogxK
U2 - 10.1111/j.1749-6632.2010.05390.x
DO - 10.1111/j.1749-6632.2010.05390.x
M3 - Conference contribution
C2 - 20392229
AN - SCOPUS:77950647414
SN - 9781573317856
T3 - Annals of the New York Academy of Sciences
SP - 139
EP - 144
BT - Skeletal Biology and Medicine
PB - Blackwell Publishing Inc.
ER -