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Review
. 2022 Dec 17:2022:7299005.
doi: 10.1155/2022/7299005. eCollection 2022.

Role of Advanced Glycation End Products in Intervertebral Disc Degeneration: Mechanism and Therapeutic Potential

Fengguang Yang  1   2   3   4   5 , Daxue Zhu  1   2   3   4 , Zhaoheng Wang  1   2   3   4 , Yingping Ma  1   2 , Liangzeng Huang  1   2   3   4 , Xuewen Kang  1   2   3   4 , Bing Ma  1   2   3   4
Affiliations
Review

Role of Advanced Glycation End Products in Intervertebral Disc Degeneration: Mechanism and Therapeutic Potential

Fengguang Yang et al. Oxid Med Cell Longev. .

Abstract

The incidence of low back pain caused by lumbar disc degeneration is high, and it can lead to loss of work ability and impose heavy social and economic burdens. The pathogenesis of low back pain is unclear, and there are no effective treatments. With age, the deposition of advanced glycation end products (AGEs) in intervertebral disc (IVD) gradually increases and is accelerated by diabetes and a high-AGEs diet, leading to destruction of the annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP) and finally intervertebral disc degeneration (IDD). Reducing the accumulation of AGEs in IVD and blocking the transmission of downstream signals caused by AGEs have a significant effect on alleviating IDD. In this review, we summarize the mechanism by which AGEs induce IDD and potential treatment strategies.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The general process of AGEs formation. CML: N-carboxymethyllysine; CEL: N-carboxyethyllysine; GOLD: glyoxal-lysine dimer; MOLD: methylglyoxal-lysine dimer; GLAP: glyceraldehyde-derived pyridinium compound.
Figure 2
Figure 2
Mechanisms of AGEs-induced apoptosis (or senescence) of nucleus pulposus cells through endoplasmic reticulum and mitochondrial pathways. AGEs: advanced glycation end products; IP3: inositol 1,4,5-trisphosphate; PLC: phospholipase C; Rya: ryanodine; Xec: xestospongin C; RyR: ryanodine receptor; IP3R: inositol 1,4,5-triphosphate receptor (U73122, xec, and RYA are calcium antagonists of PLC, IP3R, and RyR, respectively); SERCA: sarco/endoplasmic reticulum Ca2+-ATPase; UPR: unfolded protein response; ROS: reactive oxygen species; CHOP: C/EBP homologous protein; ATF6: activating transcription factor 6; PERK: protein kinase-like endoplasmic reticulum kinase; IRE1α: inositol-requiring protein 1α; MSC-exos: mesenchymal stem cells-exosomes; AKT: protein kinase B; ERK: extracellular regulated protein kinases; AMPK: adenosine monophosphate-activated protein kinase; PGC-1α: peroxisome proliferator-activated receptor-γ coactivator 1α; NMN: nicotinamide mononucleotide; SIRT3: Sirtuin3; NAC: N-acetyl-L-cysteine; PTP: permeability transition pore; ER stress: endoplasmic reticulum stress; ER-phagy: endoplasmic reticulum-phagy.
Figure 3
Figure 3
Mechanism of AGEs-induced ECM degradation. AGEs: advanced glycation end products; BRD4: bromodomain-containing protein 4; ERK: extracellular regulated protein kinase; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor kappa-B; GAG: glycosaminoglycan; ADAMTS-5: a disintegrin and metalloproteinase with thrombospondin motif-5.
Figure 4
Figure 4
Mechanisms of AGEs-induced apoptosis of AF cells through mitochondrial pathways. AGEs: advanced glycation end products; NAC: N-acetyl-L-cysteine; ROS: reactive oxygen species; Cyto-c: cytochrome c.
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