NPY signalling pathway in bone homeostasis: Y1 receptor as a potential drug target

Neuropeptide (NPY) is a neurotransmitter widely distributed in central and peripheral nervous system that has been implicated in several physiological processes through activation of five different Y receptors: Y1, Y2, Y4, Y5, and y6. NPY system has been extensively studied for the last decades due to its implications in a wide variety of physiological processes. For this purpose a diversity of sophisticated animal models and receptors agonists and antagonists has been developed to better understand its actions throughout body homeostasis. Consequently, NPY and its receptors have recently emerged as a potential regulator of bone homeostasis. This is supported by the demonstration of an increase of bone mass in mice lacking Y1 or Y2 receptor genes. Recent findings revealed Y1 receptor as a potential drug target candidate for prevention and treatment of bone loss. Indeed, it has been demonstrated that osteoblasts express Y1 receptor while no other Y receptor was detected in these cells, implicating Y1 receptor signalling in the local control of bone turnover. In this review, we have summarized the findings obtained from studies on NPY system in skeletogenesis focusing on Y1 receptor.