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

Abstract

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.

Severity of Idiopathic Scoliosis Is Associated with Differential Methylation: An Epigenome-Wide Association Study of Monozygotic Twins with Idiopathic Scoliosis

“…2. The NPY gene encodes a neuropeptide expressed throughout the central and peripheral nervous systems [108] and is an essential regulator of bone homeostasis and metabolism [109]. NPY is also a local regulator of osteoblastic lineage and is responsive to mechanical stimuli with potential roles in fracture healing and osteoarthritis [109].…”

“…The NPY gene encodes a neuropeptide expressed throughout the central and peripheral nervous systems [108] and is an essential regulator of bone homeostasis and metabolism [109]. NPY is also a local regulator of osteoblastic lineage and is responsive to mechanical stimuli with potential roles in fracture healing and osteoarthritis [109]. The WNT10A gene is a member of the WNT gene class and functions within the WNT10A/β-catenin signaling pathway in regulation of adult epithelial proliferation [110,111], mesenchymal stem cell regulation by stimulating osteoblastogenesis [112], coordination of vertebrate segmentation, and motile cilia function [113].…”

Update on the Role of Neuropeptide Y and Other Related Factors in Breast Cancer and Osteoporosis

“…Studies have shown that NPY treatment can promote the proliferation of bone marrow stem cells, promote their migration to the lesion area, and participate in the osteogenic differentiation of bone marrow stem cells (16). In addition, NPY and its receptor can regulate the proliferation of HSCs, promote their entry into peripheral blood, and increase the abundance of osteoblasts (16,91,92). Collectively, these studies suggest that NPY can be used in the treatment of osteoporosis with stem cells.…”

“…In recent years, the effects of NPY on BMSCs and hematopoietic stem cells (HSCs) have been studied. Studies have shown that NPY treatment can promote the proliferation of bone marrow stem cells, promote their migration to the lesion area, and participate in the osteogenic differentiation of bone marrow stem cells (16). In addition, NPY and its receptor can regulate the proliferation of HSCs, promote their entry into peripheral blood, and increase the abundance of osteoblasts (16,91,92).…”

“…NPY acts through NPY receptors (NPYRs), including Y1, Y2, Y4, Y5, and Y6 receptors that have been cloned in mammals (11,12). NPY plays an important role in the nervous, immune, and endocrine systems (11,(13)(14)(15) and can affect the proliferation, apoptosis, differentiation, migration, mobilization, and cytokine secretion of different cell types (16). Additionally, NPY has recently been found to play a role in the progression of breast cancer (17)(18)(19) and osteoporosis (20,21).…”