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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Neuropeptide Y-based recombinant peptides ameliorate bone loss in mice by regulating hematopoietic stem/progenitor cell mobilization

  • Park, Min Hee (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Kim, Namoh (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Jin, Hee Kyung (Stem Cell Neuroplasticity Research Group, Kyungpook National University) ;
  • Bae, Jae-sung (Stem Cell Neuroplasticity Research Group, Kyungpook National University)
  • Received : 2016.11.15
  • Accepted : 2016.12.19
  • Published : 2017.03.31
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Abstract

Ovariectomy-induced bone loss is related to an increased deposition of osteoclasts on bone surfaces. We reported that the 36-amino-acid-long neuropeptide Y (NPY) could mobilize hematopoietic stem/progenitor cells (HSPCs) from the bone marrow to the peripheral blood by regulating HSPC maintenance factors and that mobilization of HSPCs ameliorated low bone density in an ovariectomy-induced osteoporosis mouse model by reducing the number of osteoclasts. Here, we demonstrated that new NPY peptides, recombined from the cleavage of the full-length NPY, showed better functionality for HSPC mobilization than the full-length peptide. These recombinant peptides mediated HSPC mobilization with greater efficiency by decreasing HSPC maintenance factors. Furthermore, treatment with these peptides reduced the number of osteoclasts and relieved ovariectomy-induced bone loss in mice more effectively than treatment with full-length NPY. Therefore, these results suggest that peptides recombined from full-length NPY can be used to treat osteoporosis.

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References

  1. van den Bergh JP, van Geel TA and Geusens PP (2012) Osteoporosis, frailty and fracture: implications for case finding and therapy. Nat Rev Rheumatol 8, 163-172 https://doi.org/10.1038/nrrheum.2011.217
  2. Manolagas SC (2000) Sex Steroids and Bone. Endocr Rev 21, 115-137
  3. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285, 785-795 https://doi.org/10.1001/jama.285.6.785
  4. Kim TH, Jung JW, Ha BG et al (2011) The effects of luteolin on osteoclast differentiation, functionin vitro and ovariectomy-induced bone loss. J Nutr Biochem 22, 8-15 https://doi.org/10.1016/j.jnutbio.2009.11.002
  5. Kim T, Ha H, Shim KS, Cho WK and Ma JY (2013) The anti-osteoporotic effect of Yijung-tang in an ovariectomized rat model mediated by inhibition of osteoclast differentiation. J Ethnopharmacol 146, 83-89 https://doi.org/10.1016/j.jep.2012.11.037
  6. Takayanagi H (2007) Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7, 292-304 https://doi.org/10.1038/nri2062
  7. Ding L, Saunders TL, Enikolopov G and Morrison SJ (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481, 457-462 https://doi.org/10.1038/nature10783
  8. Butler JM, Nolan DJ, Vertes EL et al (2010) Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6, 251-264 https://doi.org/10.1016/j.stem.2010.02.001
  9. Levesque JP, Helwani FM and Winkler IG (2010) The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia 24, 1979-1992 https://doi.org/10.1038/leu.2010.214
  10. Arai F, Hirao A, Ohmura M et al (2004) Tie2/angiopoietin-1 signaling regulates hematopoietic stem cells quiescence in the bone marrow niche. Cell 118, 149-161 https://doi.org/10.1016/j.cell.2004.07.004
  11. Sugiyama T, Kohara H, Noda M and Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25, 977-988 https://doi.org/10.1016/j.immuni.2006.10.016
  12. Tanaka Y, Morimoto I, Nakano Y et al (1995) Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1. J Bone Miner Res 10, 1462-1469
  13. Jung Y, Wang J, Schneider A et al (2006) Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone 38, 497-508 https://doi.org/10.1016/j.bone.2005.10.003
  14. Mendez-Ferrer S, Michurina TV, Ferraro F et al (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466, 829-834 https://doi.org/10.1038/nature09262
  15. Katayama Y, Battista M, Kao WM et al (2006) Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124, 407-421 https://doi.org/10.1016/j.cell.2005.10.041
  16. Im JY, Min WK, Park MH et al (2014) AMD3100 improves ovariectomy-induced osteoporosis in mice by facilitating mobilization of hematopoietic stem/progenitor cells. BMB Rep 47, 439-444 https://doi.org/10.5483/BMBRep.2014.47.8.159
  17. Ishii M, Egen JG, Klauschen F et al (2009) Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458, 524-528 https://doi.org/10.1038/nature07713
  18. Zukowska-Grojec Z (1995) Neuropeptide Y. A novel sympathetic stress hormone and more. Ann NY Acad Sci 771, 219-233 https://doi.org/10.1111/j.1749-6632.1995.tb44683.x
  19. Kalra SP and Kalra PS (2004) NPY and cohorts in regulation appetite, obesity and metabolic syndrome: beneficial effects of gene therapy. Neuropeptides 38, 201-211 https://doi.org/10.1016/j.npep.2004.06.003
  20. Kuo LE, Kitlinska JB, Tilan JU et al (2007) Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med 13, 803-811 https://doi.org/10.1038/nm1611
  21. Park MH, Jin HK, Min WK et al (2015) Neuropeptide Y regulates the hematopoietic stem cell microenvironment and prevents nerve injury in the bone marrow. EMBO J 34, 1648-1660 https://doi.org/10.15252/embj.201490174
  22. Park MH, Lee JK, Kim N et al (2016) Neuropeptide Y Induces Hematopoietic Stem/Progenitor Cell Mobilization by Regulating Matrix Metalloproteinase-9 Activity Through Y1 Receptor in Osteoblasts. Stem Cells 34, 2145-2156 https://doi.org/10.1002/stem.2383
  23. Rose JB, Crews L, Rockenstein E et al (2009) Neuropeptide Y fragments derived from neprilysin processing are neuroprotective in a transgenic model of Alzheimer's disease. J Neurosci 29, 1115-1125 https://doi.org/10.1523/JNEUROSCI.4220-08.2009
  24. Ehninger A and Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med 208, 421-428 https://doi.org/10.1084/jem.20110132
  25. Bae JS, Furuya S, Shinoda Y et al (2005) Neurodegeneration augments the ability of bone marrow-derived mesenchymal stem cells to fuse with Purkinje neurons in Niemann-Pick type C mice. Hum Gene Ther 16, 1006-1011 https://doi.org/10.1089/hum.2005.16.1006

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