title: Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts.
abstract: Hematopoietic stem/progenitor cell (HSPC) mobilization is an essential homeostatic process regulated by the interaction of cellular and molecular components in bone marrow niches. It has been shown by others that neurotransmitters released from the sympathetic nervous system regulate HSPC egress from bone marrow to peripheral blood. In this study, we investigate the functional role of neuropeptide Y (NPY) on this process. NPY deficient mice had significantly impaired HSPC mobilization due to increased expression of HSPC maintenance factors by reduction of matrix metalloproteinase-9 (MMP-9) activity in bone marrow. Pharmacological or endogenous elevation of NPY led to decrease of HSPC maintenance factors expression by activating MMP-9 in osteoblasts, resulting in HSPC mobilization. Mice in which the Y1 receptor was deleted in osteoblasts did not exhibit HSPC mobilization by NPY. Furthermore, NPY treatment in ovariectomized mice caused reduction of bone loss due to HSPC mobilization. These results suggest a new role of NPY on HSPC mobilization, as well as the potential therapeutic application of this neuropeptide for stem cell-based therapy. Stem Cells 2016;34:2145-2156.
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Kyungpook National University, Daegu, Korea.|Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.|Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
authors.forename: Min Hee
authors.initials: MH
authors.lastname: Park
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Kyungpook National University, Daegu, Korea.|Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.|Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
authors.forename: Jong Kil
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Kyungpook National University, Daegu, Korea.|Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.|Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
authors.forename: Namoh
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Woo-Kie
authors.initials: WK
authors.lastname: Min
authors.affiliation: Department of Radiation Oncology, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Kyoung-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Orthopaedics, Kyoto University, Kyoto, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Neuroscience Research Program, Neuroscience Division, Garvan Institute of Medical Research, Sydney, Australia.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Kyungpook National University, Daegu, Korea.|Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: Hee Kyung
authors.initials: HK
authors.lastname: Jin
authors.affiliation: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Kyungpook National University, Daegu, Korea.|Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.|Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002633:Chemotaxis; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006706:Homeostasis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000172:deficiency / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
chemical_list: D009478:Neuropeptide Y; D019718:Receptors, CXCR4; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D020780:Matrix Metalloproteinase 9
keywords: Bone loss; Bone marrow environment; Hematopoietic stem/progenitor cell; Mobilization; Neuropeptide Y