LCN2 overexpression in bone enhances the hematopoietic compartment via modulation of the bone marrow microenvironment. Issue 11 (21st February 2017)

• Record Type: Journal Article
• Authors: Costa, Delfina; Principi, Elisa; Lazzarini, Edoardo; Descalzi, Fiorella; Cancedda, Ranieri; Castagnola, Patrizio; Tavella, Sara
• Is Part Of: Journal of cellular physiology. Volume 232:Issue 11(2017:Nov.)
• Page Start: 3077
• Page End: 3087
• Publication Date: 2017-02-21
• Subjects: bone marrow microenvironment -- hematopoietic cells -- lipocalin‐2 -- transgenic mice; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.25755
• Languages: English
• ISSNs: 0021-9541

Abstract

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. Abstract : The overexpression of LCN2 in bone stimulates the expansion of the HSC by inducing pro‐retention factors and inhibiting pro‐egress signals for hematopoietic stem cells.