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

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish
Pages (from-to)2145-2156
Number of pages12
JournalStem Cells
Volume34
Issue number8
DOIs
StatePublished - 1 Aug 2016

Keywords

  • Bone loss
  • Bone marrow environment
  • Hematopoietic stem/progenitor cell
  • Mobilization
  • Neuropeptide Y

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