AMPK as a Potential Therapeutic Target for Intervertebral Disc Degeneration.

Zhen Wang,Yang Jiao,Jianxiong Shen,Erwei Feng

doi:10.3389/fmolb.2021.789087

Abstract

As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.

Highlights

Low back pain (LBP) is one of the most common complaints in the clinics of orthopedics
Despite controversies on the activity and function of AMP-activated protein kinase (AMPK) in intervertebral disc degeneration (IDD), AMPK participates in the pathogenesis of IDD
The regulation of AMPK in IDD progression is attributed to its modulation on a wide range of pivotal pathophysiological changes, including cell apoptosis, senescence, inflammation, oxidative damage, extracellular matrix (ECM) destruction, etc

Summary

INTRODUCTION

Low back pain (LBP) is one of the most common complaints in the clinics of orthopedics. Multiple factors have been recognized involved in the progression of IDD, such as ageing, smoking, diabetes mellitus (DM), obesity, abnormal mechanical load and genetic predisposition (Figure 1) (Kim et al, 2009; Le Maitre et al, 2007; Jeong et al, 2014; Desmoulin et al, 2020; Maclean et al, 2004; Walsh and Lotz, 2004; Wuertz et al, 2009; Kalb et al, 2012; Martirosyan et al, 2016; Alpantaki et al, 2019; Kakadiya et al, 2020; Livshits et al, 2001; Chen et al, 2018; Cannata et al, 2020) In response to those risk factors, various crucial pathological processes develop, including the loss of resident IVD cells, ECM remodeling, inflammation and oxidative stress (Figure 1) (Gruber and Hanley, 1998; Nasto et al, 2013; Suzuki et al, 2015; Lyu et al, 2021).

DISCUSSION

SUMMARY AND OUTLOOK