RANK deletion in NPY neurons attenuates estrogen deficiency related bone loss

Abstract

The RANKL pathway is known to be an important aspect of the pathogenesis of estrogen‐deficiency induced bone loss. RANK deletion specifically in NPY neurons has been shown to enhance the ability of the skeleton to match increases in body weight caused by high fat diet feeding, likely via the modulation of NPY levels. Here, we use ovariectomy in female mice to show that RANK deletion in NPY neurons attenuates bone loss caused by long‐term estrogen deficiency, particularly in the vertebral compartment. Ovariectomy led to a reduction in NPY expression levels in the arcuate nucleus of NPY ^cre/+ ;RANK ^lox/lox mice compared to NPY ^cre/+ ;RANK ^lox/+ controls. As NPY deficient mice also displayed a similar protection against ovariectomy induced bone loss, modulation of hypothalamic NPY signalling is the likely mechanism behind the protection from bone loss in the NPY ^cre/+ ;RANK ^lox/lox mice.

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