IGF Signaling in Intervertebral Disc Health and Disease

Hui Lin,Yan Xiao,Zengwu Shao,Xiangcheng Qing,Shuo Tian,Yizhong Peng,Ling Wu

doi:10.3389/fcell.2021.817099

Abstract

Low back pain (LBP) is a common musculoskeletal symptom, which brings a lot of pain and economic loss to patients. One of the most common causes of LBP is intervertebral disc degeneration (IVDD). However, pathogenesis is still debated, and therapeutic options are limited. Insulin-like growth factor (IGF) signaling pathways play an important role in regulating different cell processes, including proliferation, differentiation, migration, or cell death, which are critical to the homeostasis of tissues and organs. The IGF signaling is crucial in the occurrence and progression of IVDD. The activation of IGF signaling retards IVDD by increasing cell proliferation, promoting extracellular matrix (ECM) synthesis, inhibiting ECM decomposition, and preventing apoptosis and senescence of disc cells. However, abnormal activation of IGF signaling may promote the process of IVDD. IGF signaling is currently considered to have a promising treatment prospect for IVDD. An in-depth understanding of the role of IGF signaling in IVDD may help find a novel approach for IVDD treatment.

Highlights

Intervertebral disc degeneration (IVDD) is a paramount contributor to low back pain and is a leading cause of disability that reduces the quality of life and causes economic loss (Feng et al, 2017; Choi et al, 2019)
The insulin-like growth factor (IGF) signaling pathways play an important role in regulating various cell activities, including proliferation, differentiation, migration, or cell death, which are critical to the homeostasis of tissues and organs (Duan and Xu, 2005; Rafacho et al, 2009; Lunn et al, 2015)
Studies have reported that the expressions of IGF are significantly abnormal in degenerative IVD tissues and cells, and it is involved in multiple pathological processes of disc degeneration by participating in cell proliferation, programmed death, degeneration and synthesis of extracellular matrix (ECM) (Tao et al, 2015; Chen et al, 2020; Zhao et al, 2020)

Summary

Introduction

Intervertebral disc degeneration (IVDD) is a paramount contributor to low back pain and is a leading cause of disability that reduces the quality of life and causes economic loss (Feng et al, 2017; Choi et al, 2019). Several studies have demonstrated that IGF signaling activation slows IVDD by increasing ECM synthesis, cell proliferation, and inhibiting inflammatory responses, ECM degradation, and cell apoptosis, which are primarily regulated by the PI3K/Akt and MEK/ERK pathways (Pratsinis and Kletsas, 2007; Mavrogonatou and Kletsas, 2010; Pratsinis et al, 2012; Wei et al, 2013; Liu et al, 2015; Tao et al, 2015; Xu et al, 2019; Tian et al, 2020).

Results

Conclusion