IBMS BoneKEy | BoneKEy Watch

New mechanoresponsive gene helps regulate bone homeostasis



DOI:10.1038/bonekey.2015.63

Lcn2, which codes for the adipokine lipocalin 2, was shown to be the most upregulated gene in mouse calvarial osteoblasts subjected to simulated microgravity, according to a previously published global transcriptome analysis. This study investigated the properties of this gene and its role in bone homeostasis in humans and in mice.

Healthy male volunteers showed a significant time-dependent increase in serum levels of lipocalin 2 when undergoing a controlled period of bed rest. In vivo Lcn2 regulation was then studied in mice subjected to mechanical unloading by one of three methods; tail suspension, transient muscle paralysis by botulin toxin A (Botox), or genetically, in a muscular dystrophy (MDX) model.

Lcn2 expression increased in the long bones of mice subjected to mechanical unloading, irrespective of the method used. This increase was counteracted when the mice were allowed to exercise. Transfection to primary osteoblasts suggested that Lcn2 works upstream of the Runx2, possibly representing a novel primary osteoblast differentiation regulatory pathway. The authors suggest that this gene is important in the osteoblast response to mechanical loading and could play a role in the development of osteoporosis that is induced by aging, muscle impairment or extended bed rest.

Editor’s comment. All experiments were performed in male volunteers or female mice. Although the authors claim that the key experiments were repeated in male mice, the question of sex-specificity needs to be specifically tested.


Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.