Interactions between kisspeptin and bone: Cellular mechanisms, clinical evidence, and future potential

Abstract

The neuropeptide kisspeptin and its cognate receptor have been extensively studied in reproductive physiology, with diverse and well-established functions, including as an upstream regulator of pubertal onset, reproductive hormone secretion, and sexual behavior. Besides classical reproduction, both kisspeptin and its receptor are extensively expressed in bone-resorbing osteoclasts and bone-forming osteoblasts, which putatively permits direct bone effects. Accordingly, this sets the scene for recent compelling findings derived from in vitro experiments through to in vivo and clinical studies revealing prominent regulatory interactions for kisspeptin signaling in bone metabolism, as well as certain oncological aspects of bone metabolism. Herein, we comprehensively examine the experimental evidence obtained to date supporting the interaction between kisspeptin and bone. A comprehensive understanding of this emerging facet of kisspeptin biology is fundamental to exploiting the future therapeutic potential of kisspeptin-based medicines as a novel strategy for treating bone-related disorders.