Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2020; 12(9): 986-1000
Published online Sep 26, 2020. doi: 10.4252/wjsc.v12.i9.986
Mechanisms of action of neuropeptide Y on stem cells and its potential applications in orthopaedic disorders
Jian-Qun Wu, Nan Jiang, Bin Yu
Jian-Qun Wu, Department of Orthopedics and Traumatology, Huadu District People’s Hospital, Guangzhou 510800, Guangdong Province, China
Nan Jiang, Bin Yu, Division of Orthopaedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Nan Jiang, Bin Yu, Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: Wu JQ and Jiang N contributed equally to this study; Jiang N and Yu B contributed to the conception and design; Wu JQ contributed to the literature search; Wu JQ and Jiang N wrote the paper; all authors contributed to the critical revision and approval of the final version.
Supported by the National Natural Science Foundation of China, No. 81830079; Guangzhou Health Science and Technology Project, No. 20191A011116; and Science and Technology Project of Guangzhou Huadu District, No. 18-HDWS-003.
Conflict-of-interest statement: The authors certify that they, or any members of their immediate families, have no funding or commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Bin Yu, MD, PhD, Professor, Surgeon, Department of Orthopedics, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Avenue, Baiyun District, Guangzhou 510515, Guangdong Province, China.
Received: March 25, 2020
Peer-review started: March 25, 2020
First decision: April 29, 2020
Revised: May 25, 2020
Accepted: June 2, 2020
Article in press: June 2, 2020
Published online: September 26, 2020

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.

Keywords: Neuropeptide Y, Bone marrow mesenchymal stem cells, Hematopoietic stem cells, Fracture, Osteoporosis, Osteoarthritis

Core tip: Neuropeptide Y (NPY) system is crucial for bone metabolism and homeostasis. NPY can regulate biological effects of different types of cells through central and peripheral nervous systems. Here, we summarize recent findings regarding the roles of NPY and its receptors in bone metabolism and homeostasis, and discuss the biological actions and underlying mechanisms of NPY on bone marrow mesenchymal stem cells, hematopoietic stem cells, endothelial cells, and chondrocytes. We also review the potential applications and efficacy of NPY and NPY receptor-targeted drugs in the treatment of fracture healing, osteoporosis, and osteoarthritis.