title: LCN2 overexpression in bone enhances the hematopoietic compartment via modulation of the bone marrow microenvironment.
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.
authors.affiliation: Dipartimento di Medicina Sperimentale, Universita' di Genova, Genova, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Costa
authors.affiliation: Dipartimento di Medicina Sperimentale, Universita' di Genova, Genova, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Principi
authors.affiliation: Dipartimento di Medicina Sperimentale, Universita' di Genova, Genova, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Lazzarini
authors.affiliation: Istituto di Bioimmagini e Fisiologia Molecolare, Consiglio Nazionale delle Ricerche, Genova, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Descalzi
authors.affiliation: Dipartimento di Medicina Sperimentale, Universita' di Genova, Genova, Italy.
authors.forename: Ranieri
authors.initials: R
authors.lastname: Cancedda
authors.affiliation: IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Castagnola
authors.affiliation: Dipartimento di Medicina Sperimentale, Universita' di Genova, Genova, Italy.|IRCCS AOU San Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tavella
mesh_terms: D016475:3T3 Cells; D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D019070:Cell Lineage; D049109:Cell Proliferation; D002633:Chemotaxis; D024042:Collagen Type I / Q000235:genetics; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D000071068:Lipocalin-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism*; D019899:Paracrine Communication; D010447:Peptide Hydrolases / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D012886:Skull / Q000166:cytology*; D055153:Stem Cell Niche
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D017077:Culture Media, Conditioned; D016207:Cytokines; D000071068:Lipocalin-2; C071332:Lcn2 protein, mouse; D010447:Peptide Hydrolases
keywords: bone marrow microenvironment; hematopoietic cells; lipocalin-2; transgenic mice