LCN2 overexpression in bone enhances the hematopoietic compartment via modulation of the bone marrow microenvironment

Delfina Costa, Elisa Principi, Edoardo Lazzarini, Fiorella Descalzi, Ranieri Cancedda, Patrizio Castagnola, Sara Tavella

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Lipocalin-2 (LCN2) is a member of the lipocalin family whose expression is modulated in several conditions, including cell differentiation, innate immunity, stress, and cancer. Although it is known that it is expressed in bone, its function in this tissue remains poorly studied. To this end, we took advantage of transgenic mice lines that expressed LCN2 driven by a bone specific type I collagen (LCN2-Tg). In the bone marrow (BM) of LCN2-Tg mice we observed an increased number of phenotypically long-term hematopoietic stem cells (LT-HSC) that also displayed a higher proliferation rate compared to wild-type controls (Wt). Furthermore, hematopoietic progenitor cells, obtained from LCN2-Tg BM showed an increased clonogenic capacity compared to those obtained from LCN2-Tg spleen, a higher concentration of serum erythropoietin and a higher number of mature erythrocytes in the peripheral blood of old LCN2-Tg animals compared to aged-matched wt. The findings of a combined increase in the BM of the LCN2-Tg mice of SDF-1, SCF, and TIMP-1 levels along with the reduction of both MMP-9 activity and cathepsin K concentration may explain the observed effects on the HSC compartment. This study shows that LCN2 overexpression in bones modifies the BM microenvironment via modulation of the expression of key secreted factors and cytokines, which in turn regulate the HSC niche behavior enhancing both HSC homing in young mice and erythrocytes production in older mice.

Original languageEnglish
JournalJournal of Cellular Physiology
Early online dateDec 22 2016
DOIs
Publication statusE-pub ahead of print - Dec 22 2016

Fingerprint

Lipocalins
Bone
Bone Marrow
Modulation
Bone and Bones
Hematopoietic Stem Cells
Cathepsin K
Lipocalin-2
Erythrocyte Count
Tissue Inhibitor of Metalloproteinase-1
Erythropoietin
Collagen Type I
Matrix Metalloproteinases
Innate Immunity
Transgenic Mice
Stem cells
Cell Differentiation
Spleen
Erythrocytes
Animals

Keywords

  • Bone marrow microenvironment
  • Hematopoietic cells
  • Lipocalin-2
  • Transgenic mice

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

LCN2 overexpression in bone enhances the hematopoietic compartment via modulation of the bone marrow microenvironment. / Costa, Delfina; Principi, Elisa; Lazzarini, Edoardo; Descalzi, Fiorella; Cancedda, Ranieri; Castagnola, Patrizio; Tavella, Sara.

In: Journal of Cellular Physiology, 22.12.2016.

Research output: Contribution to journalArticle

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AU - Cancedda, Ranieri

AU - Castagnola, Patrizio

AU - Tavella, Sara

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