Lipocalin-2 controls the expression of SDF-1 and the number of responsive cells in bone

Lipocalin-2 (LCN2) is a member of the lipocalin family, small secreted proteins functioning as modulators of many different physiological processes including cell differentiation, proliferation and apoptosis. LCN2 expression is also up-regulated in several pathological conditions, including inflammation and cancer. LCN2 synthesis has been described in epithelia, bone and cells of the immune system. Despite its wide expression the role of LCN2 remains to be fully elucidated. To better understand the role of this lipocalin in the bone/bone marrow system we generated transgenic mice over-expressing LCN2 specifically in bone under the control of a type I collagen promoter. In the bone marrow of these transgenic mice we observed an increased expression of SDF-1 that correlated with an increased number of CD34+/CXCR4+ (SDF-1 receptor) cells. To some extent, this appeared due to an enhanced cell proliferation rate. The higher level of the factor synthesis and the increased number of cells expressing its receptor was maintained during animal aging. Our results show that LCN2 could play a role in determining the number of CD34+/CXCR4+ precursor cells in the bone marrow thus contributing to the control of the bone marrow microenvironment.