The Proteolysis of ECM in Intervertebral Disc Degeneration

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 15

PMID 35163637

Authors

Huaizhen Liang

Rongjing Luo

Gaocai Li

Weifeng Zhang

Yu Song

Cao Yang

Affiliations

Soon will be listed here.

Abstract

Intervertebral disc (IVD) degeneration (IDD) is a pathological process that commonly occurs throughout the human life span and is a major cause of lower back pain. Better elucidation of the molecular mechanisms involved in disc degeneration could provide a theoretical basis for the development of lumbar disc intervention strategies. In recent years, extracellular matrix (ECM) homeostasis has received much attention due to its relevance to the mechanical properties of IVDs. ECM proteolysis mediated by a variety of proteases is involved in the pathological process of disc degeneration. Here, we discuss in detail the relationship between the IVD as well as the ECM and the role of ECM proteolysis in the degenerative process of the IVD. Targeting ECM proteolysis-associated proteases may be an effective means of intervention in IDD.

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References

Omlor G, Lorenz H, Engelleiter K, Richter W, Carstens C, Kroeber M . Changes in gene expression and protein distribution at different stages of mechanically induced disc degeneration--an in vivo study on the New Zealand white rabbit. J Orthop Res. 2006; 24(3):385-92. DOI: 10.1002/jor.20055. View

Nasto L, Robinson A, Ngo K, Clauson C, Dong Q, St Croix C . Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration. J Orthop Res. 2013; 31(7):1150-7. PMC: 3668354. DOI: 10.1002/jor.22320. View

Wang X, Tan J, Sun J, Fang P, Chen J, Yuan W . Transcriptomics Study to Determine the Molecular Mechanism by which sIL-13R2-Fc Inhibits Caudal Intervertebral Disc Degeneration in Rats. Biomed Res Int. 2020; 2020:7645989. PMC: 7443219. DOI: 10.1155/2020/7645989. View

Kague E, Turci F, Newman E, Yang Y, Robson Brown K, Aglan M . 3D assessment of intervertebral disc degeneration in zebrafish identifies changes in bone density that prime disc disease. Bone Res. 2021; 9(1):39. PMC: 8408153. DOI: 10.1038/s41413-021-00156-y. View

Liu Q, Tan Z, Xie C, Ling L, Hu H . Oxidative stress as a critical factor might involve in intervertebral disc degeneration via regulating NOXs/FOXOs. J Orthop Sci. 2021; 28(1):105-111. DOI: 10.1016/j.jos.2021.09.010. View

Wang Z, Ding X, Cao F, Zhang X, Wu J . Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells the miR-101-3p/EIF4G2 Axis. Front Bioeng Biotechnol. 2021; 9:642502. PMC: 8429483. DOI: 10.3389/fbioe.2021.642502. View

Pockert A, Richardson S, Le Maitre C, Lyon M, Deakin J, Buttle D . Modified expression of the ADAMTS enzymes and tissue inhibitor of metalloproteinases 3 during human intervertebral disc degeneration. Arthritis Rheum. 2009; 60(2):482-91. DOI: 10.1002/art.24291. View

Binch A, Cole A, Breakwell L, Michael A, Chiverton N, Cross A . Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration. Arthritis Res Ther. 2014; 16(5):416. PMC: 4177417. DOI: 10.1186/s13075-014-0416-1. View

Woods B, Vo N, Sowa G, Kang J . Gene therapy for intervertebral disk degeneration. Orthop Clin North Am. 2011; 42(4):563-74, ix. DOI: 10.1016/j.ocl.2011.07.002. View

10.

Reis Rodrigues L, Theodoro T, Matos L, Mader A, Milani C, da Silva Pinhal M . Heparanase isoform expression and extracellular matrix remodeling in intervertebral disc degenerative disease. Clinics (Sao Paulo). 2011; 66(5):903-9. PMC: 3109393. DOI: 10.1590/s1807-59322011000500030. View

11.

Seki S, Asanuma-Abe Y, Masuda K, Kawaguchi Y, Asanuma K, Muehleman C . Effect of small interference RNA (siRNA) for ADAMTS5 on intervertebral disc degeneration in the rabbit anular needle-puncture model. Arthritis Res Ther. 2009; 11(6):R166. PMC: 3003501. DOI: 10.1186/ar2851. View

12.

Wang J, Markova D, Anderson D, Zheng Z, Shapiro I, Risbud M . TNF-α and IL-1β promote a disintegrin-like and metalloprotease with thrombospondin type I motif-5-mediated aggrecan degradation through syndecan-4 in intervertebral disc. J Biol Chem. 2011; 286(46):39738-49. PMC: 3220535. DOI: 10.1074/jbc.M111.264549. View

13.

Wang X, Li C, Liang A, Peng Y, Sun J, Huang D . Regulation of a disintegrins and metalloproteinase with thrombospondin motifs 7 during inflammation in nucleus pulposus (NP) cells: role of AP-1, Sp1 and NF-κB signaling. Inflamm Res. 2016; 65(12):951-962. DOI: 10.1007/s00011-016-0978-2. View

14.

Xu H, Mei Q, He J, Liu G, Zhao J, Xu B . Correlation of matrix metalloproteinases-1 and tissue inhibitor of metalloproteinases-1 with patient age and grade of lumbar disk herniation. Cell Biochem Biophys. 2014; 69(3):439-44. DOI: 10.1007/s12013-014-9815-9. View

15.

Sivan S, Hayes A, Wachtel E, Caterson B, Merkher Y, Maroudas A . Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc. Eur Spine J. 2013; 23 Suppl 3:S344-53. DOI: 10.1007/s00586-013-2767-8. View

16.

Yao M, Zhang J, Li Z, Guo S, Zhou X, Zhang W . Marein protects human nucleus pulposus cells against high glucose-induced injury and extracellular matrix degradation at least partly by inhibition of ROS/NF-κB pathway. Int Immunopharmacol. 2020; 80:106126. DOI: 10.1016/j.intimp.2019.106126. View

17.

Liu Y, Yu T, Ma X, Xiang H, Hu Y, Chen B . Lentivirus-mediated TGF-β3, CTGF and TIMP1 gene transduction as a gene therapy for intervertebral disc degeneration in an rabbit model. Exp Ther Med. 2016; 11(4):1399-1404. PMC: 4812386. DOI: 10.3892/etm.2016.3063. View

18.

Yang B, Yang B, Erwin M, Ang L, Finkelstein J, Yee A . Versican G3 domain enhances cellular adhesion and proliferation of bovine intervertebral disc cells cultured in vitro. Life Sci. 2003; 73(26):3399-413. DOI: 10.1016/j.lfs.2003.06.018. View

19.

Gruber H, Ingram J, Hoelscher G, Zinchenko N, Norton H, Hanley Jr E . Constitutive expression of cathepsin K in the human intervertebral disc: new insight into disc extracellular matrix remodeling via cathepsin K and receptor activator of nuclear factor-κB ligand. Arthritis Res Ther. 2011; 13(4):R140. PMC: 3239383. DOI: 10.1186/ar3454. View

20.

Hiyama A, Mochida J, Iwashina T, Omi H, Watanabe T, Serigano K . Transplantation of mesenchymal stem cells in a canine disc degeneration model. J Orthop Res. 2008; 26(5):589-600. DOI: 10.1002/jor.20584. View