Intracerebroventricular injection of sclerostin reduced social hierarchy and impaired neuronal dendritic complexity in mice.

An increasing number of studies have demonstrated extensive functional links between bone and the brain. As a novel endocrine organ, bone has received increasing attention for its upregulatory functions in the brain. Sclerostin, a novel bone-derived endocrine molecule, secreted by osteocytes, can inhibit the bone morphogenetic protein (BMP) and wingless/integrated (Wnt) signaling pathways to regulate bone formation, but its effects on the central nervous system and neurosocial behaviors are unknown. This study investigated the effects of intracerebroventricular sclerostin injection on social-emotional behaviors in adult mice. The results showed that acute elevation of sclerostin levels in the brain could induce anxiety-like behaviors and reduce the social hierarchy of mice while reducing the dendritic complexity of pyramidal neurons in the mouse hippocampus. These data suggested that sclerostin may regulate social-emotional behaviors, providing new evidence for the existence of a bone-brain axis, new insights into the regulation of social behaviors by bone-derived endocrine molecules, and a new direction for the study of individual emotional behavior regulation.