Mechanisms of action of neuropeptide Y on stem cells and its potential applications in orthopaedic disorders

Musculoskeletal disorders are the leading causes of disability and result in reduced quality of life. The neuro-osteogenic network is one of the most promising fields in orthopaedic research. Neuropeptide Y (NPY) system has been reported to be involved in the regulations of bone metabolism and homeostasis, which also provide feedback to the central NPY system via NPY receptors. Currently, potential roles of peripheral NPY in bone metabolism remain unclear. Growing evidence suggests that NPY can regulate biological actions of bone marrow mesenchymal stem cells, hematopoietic stem cells, endothelial cells, and chondrocytes via a local autocrine or paracrine manner by different NPY receptors. The regulative activities of NPY may be achieved through the plasticity of NPY receptors, and interactions among the targeted cells as well. In general, NPY can influence proliferation, apoptosis, differentiation, migration, mobilization, and cytokine secretion of different types of cells, and play crucial roles in the development of bone delayed/non-union, osteoporosis, and osteoarthritis. Further basic research should clarify detailed mechanisms of action of NPY on stem cells, and clinical investigations are also necessary to comprehensively evaluate potential applications of NPY and its receptor-targeted drugs in management of musculoskeletal disorders.