Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts

Min Hee Park; Jong Kil Lee; Namoh Kim; Woo-Kie Min; Jeong Eun Lee; Kyoung-Tae Kim; Haruhiko Akiyama; Herbert Herzog; Edward H Schuchman; Hee Kyung Jin; Jae-Sung Bae

doi:10.1002/stem.2383

Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts

Stem Cells. 2016 Aug;34(8):2145-56. doi: 10.1002/stem.2383. Epub 2016 May 18.

Authors

Min Hee Park^{1

2

3}, Jong Kil Lee^{1

2

3}, Namoh Kim^{1

2

3}, Woo-Kie Min⁴, Jeong Eun Lee⁵, Kyoung-Tae Kim⁶, Haruhiko Akiyama⁷, Herbert Herzog⁸, Edward H Schuchman⁹, Hee Kyung Jin^{1

10}, Jae-Sung Bae^{1

2

3}

Affiliations

¹ Stem Cell Neuroplasticity Research Group, Kyungpook National University, Kyungpook National University, Daegu, Korea.
² Department of Physiology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
³ Department of Biomedical Science, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, Korea.
⁴ Department of Orthopaedic Surgery, Kyungpook National University Hospital, Daegu, Korea.
⁵ Department of Radiation Oncology, Kyungpook National University Hospital, Daegu, Korea.
⁶ Department of Neurosurgery School of Medicine, Kyungpook National University, Daegu, Korea.
⁷ Department of Orthopaedics, Kyoto University, Kyoto, Japan.
⁸ Neuroscience Research Program, Neuroscience Division, Garvan Institute of Medical Research, Sydney, Australia.
⁹ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁰ Department of Laboratory Animal Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.

PMID: 27090492
DOI: 10.1002/stem.2383

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.

Keywords: Bone loss; Bone marrow environment; Hematopoietic stem/progenitor cell; Mobilization; Neuropeptide Y.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone and Bones / metabolism
Chemotaxis
Female
Hematopoietic Stem Cell Mobilization*
Homeostasis
Matrix Metalloproteinase 9 / metabolism*
Mice, Inbred C57BL
Neuropeptide Y / deficiency
Neuropeptide Y / metabolism*
Osteoblasts / cytology
Osteoblasts / enzymology
Osteoblasts / metabolism*
Receptors, CXCR4 / metabolism
Receptors, Neuropeptide Y / metabolism*

Substances

Neuropeptide Y
Receptors, CXCR4
Receptors, Neuropeptide Y
neuropeptide Y-Y1 receptor
Matrix Metalloproteinase 9