The last decade has seen a marked increase in our understanding of the extent and importance of neural processes upon the regulation of bone mass, revealing that neural inputs are fundamental to bone homeostasis. Moreover, novel relationships have demonstrated between bone and other systems, namely energy and glucose homeostasis and the endocrine system. Our group has examined of the relationship between bone homeostasis and the neuropeptide Y (NPY) system, a fundamental regulator of energy homeostasis and endocrine function.
We have shown that signals processed in the hypothalamus of the brain, and travelling through the sympathetic nervous system exert powerful regulatory influences upon the osteoblast, and that by inhibiting these signals we can stimulate the production of bone by these cells. Our studies of NPY control of bone mass revealed actions within the hypothalamus and osteoblast to inhibit bone formation.
Moreover, central actions of NPY provide a mechanism whereby responses to energy homeostasis are coordinated. Bone homeostasis is amongst the processes regulated by these central NPY-mediated energy homeostatic processes.
The hypothalamus is best known for regulating endocrine pathways through the pituitary, suggesting the possibility of interaction between the neural and hormonal pathways form the hypothalamus. Indeed we have identified marked co-regulation by these two pathways. NPY signalling has been shown to interact with 2 major hormonal axis affecting bone mass; sex steroids and glucocorticoids, with influences upon bone mass.
Our most recent work demonstrates NPY’s involvement in unique endocrine actions of the osteoblast: Regulating control of glucose homeostasis through specific signalling within the osteoblast, and regulating bone mass through central signalling of osteocalcin, thereby closing the brain/bone circuit.
This work illustrates the importance of neural signals to bone homeostasis and the interrelation of this signalling pathway with known skeletal modulators.