TY - JOUR
T1 - Matrix-embedded osteocytes regulate mobilization of hematopoietic stem/progenitor cells
AU - Asada, Noboru
AU - Katayama, Yoshio
AU - Sato, Mari
AU - Minagawa, Kentaro
AU - Wakahashi, Kanako
AU - Kawano, Hiroki
AU - Kawano, Yuko
AU - Sada, Akiko
AU - Ikeda, Kyoji
AU - Matsui, Toshimitsu
AU - Tanimoto, Mitsune
N1 - Funding Information:
We would like to thank the following: Drs. Hidetsugu Tsujigiwa and Hitoshi Nagatsuka (Okayama University) for the technical help and valuable suggestions on immunohistological analysis of bone; Dr. Hiroshi Kamioka (Okayama University) for the superb advice about osteocyte staining and for stimulating discussions; and Dr. Toshitaka Oohashi (Okayama University) for the technical help on making frozen sections. This work was supported by the Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science (#23390251 to Y. Katayama) and for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology in Japan (#23118517 to Y. Katayama). N.A. performed all experiments and wrote the manuscript; M.S., K.M., K.W., H.K., Y. Kawano, and A.S. helped with animal maintenance, tissue sample preparation, and qRT-PCR; K.I. and T.M. supervised the studies for DMP-1 DTR Tg mice; M.T. supervised the studies for surgical denervation and kl/kl mice; and Y. Katayama supervised all experiments and wrote the manuscript. The authors declare no competing financial interests.
PY - 2013/6/6
Y1 - 2013/6/6
N2 - The bone marrow (BM) niche comprises multiple cell types that regulate hematopoietic stem/progenitor cell (HSPC) migration out of the niche and into the circulation. Here, we demonstrate that osteocytes, the major cellular component of mature bone, are regulators of HSPC egress. Granulocyte colony-stimulating factor (G-CSF), used clinically to mobilize HSPCs, induces changes in the morphology and gene expression of the osteocytic network that precedes changes in osteoblasts. This rapid response is likely under control of the sympathetic nervous system, since osteocytes express the β2-adrenergic receptor and surgical sympathectomy prevents it. Mice with targeted ablation of osteocytes or a disrupted osteocyte network have comparable numbers of HSPCs in the BM but fail to mobilize HSPCs in response to G-CSF. Taken together, these results indicate that the BM/bone niche interface is critically controlled from inside of the bone matrix and establish an important physiological role for skeletal tissues in hematopoietic function.
AB - The bone marrow (BM) niche comprises multiple cell types that regulate hematopoietic stem/progenitor cell (HSPC) migration out of the niche and into the circulation. Here, we demonstrate that osteocytes, the major cellular component of mature bone, are regulators of HSPC egress. Granulocyte colony-stimulating factor (G-CSF), used clinically to mobilize HSPCs, induces changes in the morphology and gene expression of the osteocytic network that precedes changes in osteoblasts. This rapid response is likely under control of the sympathetic nervous system, since osteocytes express the β2-adrenergic receptor and surgical sympathectomy prevents it. Mice with targeted ablation of osteocytes or a disrupted osteocyte network have comparable numbers of HSPCs in the BM but fail to mobilize HSPCs in response to G-CSF. Taken together, these results indicate that the BM/bone niche interface is critically controlled from inside of the bone matrix and establish an important physiological role for skeletal tissues in hematopoietic function.
UR - http://www.scopus.com/inward/record.url?scp=84878889208&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878889208&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2013.05.001
DO - 10.1016/j.stem.2013.05.001
M3 - Article
C2 - 23746979
AN - SCOPUS:84878889208
SN - 1934-5909
VL - 12
SP - 737
EP - 747
JO - Cell stem cell
JF - Cell stem cell
IS - 6
ER -