Lipocalin 2 Influences Bone and Muscle Phenotype in the Mouse Model of Duchenne Muscular Dystrophy.

Lipocalin 2 (Lcn2) is an adipokine involved in bone and energy metabolism. Its serum levels correlate with bone mechanical unloading and inflammation, two conditions representing hallmarks of Duchenne Muscular Dystrophy (DMD). Therefore, we investigated the role of Lcn2 in bone loss induced by muscle failure in the mouse model of DMD. We found increased Lcn2 serum levels in mice at 1, 3, 6, and 12 months of age. Consistently, mRNA was higher in versus WT muscles. Immunohistochemistry showed Lcn2 expression in mononuclear cells between muscle fibres and in muscle fibres, thus confirming the gene expression results. We then ablated in mice, breeding them with mice (), resulting in a higher percentage of trabecular volume/total tissue volume compared to mice, likely due to reduced bone resorption. Moreover, mice presented with higher grip strength, increased intact muscle fibres, and reduced serum creatine kinase levels compared to . Consistently, blocking Lcn2 by treating 2-month-old mice with an anti-Lcn2 monoclonal antibody (Lcn2Ab) increased trabecular volume, while reducing osteoclast surface/bone surface compared to mice treated with irrelevant IgG. Grip force was also increased, and diaphragm fibrosis was reduced by the Lcn2Ab. These results suggest that Lcn2 could be a possible therapeutic target to treat DMD-induced bone loss.