Correlation between the expression levels of MMP mRNA and ADAMTS mRNA with the degree of intervertebral disc degeneration

doi:10.3969/j.issn.1673-8640.2022.02.004

Abstract

Abstract:

Objective To investigate the correlation between the expression levels of matrix metalloproteinase（MMP） mRNA and a disintegrin and metalloproteinase with thrombospondin motifs（ADAMTS） mRNA with the degree of intervertebral disc degeneration. Methods A total of 160 disc degenerative disease patients were enrolled,and according to the results of magnetic resonance imaging（MRI） and Pfirrmann classification method,they were classified into Ⅰ level（30 cases）,Ⅱ level（32 cases）,Ⅲ level（35 cases）,Ⅳ level（33 cases） and Ⅴ level（30 cases）. The expressions of MMP-1 mRNA,MMP-3 mRNA,MMP-9 mRNA,MMP-13 mRNA,ADAMTS-1 mRNA,ADAMTS-4 mRNA,ADAMTS-5 mRNA,interleukin（IL）-1α mRNA,IL-1β mRNA,IL-6 mRNA and IL-8 mRNA in the nucleus pulposus were determined. Spearman correlation analysis was used to evaluate the correlation between each indicator and Pfirrmann classification,and Pearson correlation analysis was used to evaluate the correlation between each indicator. Results The relative expressions of MMP-3 mRNA,MMP-9 mRNA,IL-1α mRNA and IL-1β mRNA in Ⅳ and Ⅴ level groups were higher than those in Ⅰ,Ⅱ and Ⅲ level groups（P<0.05）,and those in Ⅰ,Ⅱ and Ⅲ groups were increased in turn（P<0.05）. The relative expressions of ADAMTS-4 mRNA and ADAMTS-5 mRNA were higher in Ⅲ,Ⅳ and Ⅴ level groups than those in Ⅰ and Ⅱ level groups（P<0.05）,and those in Ⅱ level group was higher than those in Ⅰ level group（P<0.05）. There was no statistical significance for the other indicators（P>0.05）. Spearman correlation analysis showed that the relative expressions of MMP-3 mRNA,MMP-9 mRNA,ADAMTS-4 mRNA,ADAMTS-5 mRNA,IL-1α mRNA and IL-1β mRNA were positively correlated with Pfirrmann classification（P<0.05）. Pearson correlation analysis showed that the relative expressions of MMP-3 mRNA,MMP-9 mRNA,ADAMTS-4 mRNA and ADAMTS-5 mRNA were positively correlated with the relative expressions of IL-1α mRNA and IL-1β mRNA（P<0.05）. Conclusions MMP-3,MMP-9,ADAMTS-4,ADAMTS-5,IL-1α and IL-1β are related to the occurrence and development of intervertebral disc degeneration,which can reflect the severity of the disease.

Key words: Matrix metalloproteinase, A disintegrin and metalloproteinase with thrombospondin motifs, Intervertebral disc, Degeneration

CLC Number:

R446.1

XU Mingyuan, XU Guisen, YANG Xiaokun, LUO Yong, GUAN Sishu, FAN Yunfei. Correlation between the expression levels of MMP mRNA and ADAMTS mRNA with the degree of intervertebral disc degeneration[J]. Laboratory Medicine, 2022, 37(2): 117-121.

Figures/Tables 3

References 21

[1]	HOY D, MARCH L, BROOKS P, et al. The global burden of low back pain:estimates from the Global Burden of Disease 2010 study[J]. Ann Rheum Dis, 2014, 73(6):968-974. DOI URL
[2]	朱薇, 贾东林, 刘晓光, 等. 慢性腰腿痛住院病人焦虑抑郁状态及其对疼痛的影响[J]. 中国疼痛医学杂志, 2017, 23(3):200-204.
[3]	WANG A M, CAO P, YEE A, et al. Detection of extracellular matrix degradation in intervertebral disc degenerationby diffusion magnetic resonance spectroscopy[J]. Magn Reson Med, 2015, 73(5):1703-1712. DOI URL
[4]	VO N V, HARTMAN R A, YURUBE T, et al. Expression and regulation of metalloproteinases and their inhibitors in intervertebral disc aging and degeneration[J]. Spine J, 2013, 13(3):331-341. DOI URL
[5]	NEIDLINGER-WILKE C, BOLDT A, BROCHHAUSEN C, et al. Molecular interactions between human cartilaginous endplates and nucleus pulposus cells:a preliminary investigation[J]. Spine(Phila Pa 1976), 2014, 39(17):1355-1364. DOI URL
[6]	PFIRRMANN C W, METZDORF A, ZANETTI M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration[J]. Spine(Phial Pa 1976), 2001, 26(17):1873-1878.
[7]	DALY C, GHOSH P, JENKIN G, et al. A review of animal models of intervertebral disc degeneration:pathophysiology,regeneration,and translation to the clinic[J]. Biomed Res Int, 2016, 2016:5952165.
[8]	BOISSON M, LEFÈVRE-COLAU M M, RANNOU F, et al. Active discopathy:a clinical reality[J]. RMD Open, 2018, 4(1):e000660.
[9]	PAPATHANASIOU I, MICHALITSIS S, HANTES M E, et al. Molecular changes indicative of cartilage degeneration and osteoarthritis development in patients with anterior cruciate ligament injury[J]. BMC Musculoskelet Disord, 2016, 17:21. DOI URL
[10]	CAREY P, LOW E, HARPER E, et al. Metalloproteinases in ovarian cancer[J]. Int J Mol Sci, 2021, 22(7):3403. DOI URL
[11]	陈彬, 卢蔚薇, 徐忠玉. 血清NT-proBNP、CRP与MMP-9在儿童川崎病中的临床意义[J]. 检验医学, 2020, 35(3):243-246.
[12]	ZHANG J F, WANG G L, ZHOU Z J, et al. Expression of matrix metalloproteinases,tissue inhibitors of metalloproteinases,and interleukins in vertebral cartilage endplate[J]. Orthop Surg, 2018, 10(4):306-311. DOI URL
[13]	TAKAHASHI M, HARO H, WAKABAYASHI Y, et al. The association of degeneration of the intervertebral disc with 5a/6a polymorphism in the promoter of the human matrix metalloproteinase-3 gene[J]. J Bone Joint Surg Br, 2001, 83(4):491-495. DOI URL
[14]	WANG X, TAN J, SUN J, et al. Transcriptomics study to determine the molecular mechanism by which sIL-13Rα2-Fc inhibits caudal intervertebral disc degeneration in rats[J]. Biomed Res Int, 2020, 2020:7645989.
[15]	PATEL K P, SANDY J D, AKEDA K, et al. Aggrecanases and aggrecanase-generated fragments in the human intervertebral disc at early and advanced stages of disc degeneration[J]. Spine(Phial Pa 1976), 2007, 32(23):2596-2603.
[16]	CHEN S, HUANG Y, ZHOU Z J, et al. Upregulation of tumor necrosis factor α and ADAMTS-5,but not ADAMTS-4,in human intervertebral cartilage endplate with modic changes[J]. Spine(Phila Pa 1976), 2014, 39(14):E817-E825. DOI URL
[17]	刘宜昕, 魏蔚, 王阳, 等. TNF-α和CRT双信号对RA患者滑膜组织NLRP3炎症小体的活化作用[J]. 检验医学, 2020, 35(4):363-369.
[18]	LI P B, TANG W J, WANG K, et al. Expressions of IL-1α and MMP-9 in degenerated lumbar disc tissues and their clinical significance[J]. Eur Rev Med Pharmacol Sci, 2017, 21(18):4007-4013.
[19]	WANG Z, HUTTON W C, YOON S T. Bone morphogenetic protein-7 antagonizes tumor necrosis factor-α-induced activation of nuclear factor κB and up-regulation of the ADAMTS,leading to decreased degradation of disc matrix macromolecules aggrecan and collagen Ⅱ[J]. Spine J, 2014, 14(3):505-512. DOI URL
[20]	WANG J, MARKOVA D, ANDERSON D G, et al. 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]. J Biol Chem, 2011, 286(46):39738-39749. DOI URL
[21]	TIAN Y, YUAN W, FUJITA N, et al. Inflammatory cytokines associated with degenerative disc disease control aggrecanase-1(ADAMTS-4) expression in nucleus pulposus cells through MAPK and NF-κB[J]. Am J Pathol, 2013, 182(6):2310-2321. DOI URL

组别	例数	MMP-1 mRNA	MMP-3 mRNA	MMP-9 mRNA	MMP-13 mRNA	ADAMTS-1 mRNA
Ⅰ级组	30	0.41±0.11	0.31±0.11	0.35±0.12	0.37±0.11	0.41±0.15
Ⅱ级组	32	0.37±0.25	0.38±0.12^*	0.43±0.15^*	0.35±0.10	0.39±0.14
Ⅲ级组	35	0.40±0.81	0.45±0.13^*#	0.61±0.14^*#	0.40±0.15	0.37±0.15
Ⅳ级组	33	0.35±0.12	0.56±0.21^*#△	0.87±0.23^*#△	0.39±0.13	0.42±0.17
Ⅴ级组	30	0.39±0.34	0.57±0.23^*#△	0.85±0.21^*#△	0.41±0.15	0.39±1.04
组别	ADAMTS-4 mRNA	ADAMTS-5 mRNA	IL-1α mRNA	IL-1β mRNA	IL-6 mRNA	IL-8 mRNA
Ⅰ级组	0.37±0.13	0.35±0.12	0.28±0.11	0.39±0.13	0.36±0.09	0.41±0.13
Ⅱ级组	0.56±0.21^*	0.47±0.14^*	0.54±0.13^*	0.57±0.15^*	0.35±0.11	0.39±0.12
Ⅲ级组	0.75±0.22^*#	0.67±0.17^*#	0.67±0.15^*#	0.75±0.17^*#	0.39±0.15	0.42±0.14
Ⅳ级组	0.94±0.25^*#	0.89±0.18^*#	0.87±0.14^*#△	0.97±0.16^*#△	0.41±0.13	0.40±0.11
Ⅴ级组	0.96±0.23^*#	0.91±0.20^*#	0.89±0.17^*#△	0.93±0.15^*#△	0.40±0.11	0.41±0.15

组别	例数	MMP-1 mRNA	MMP-3 mRNA	MMP-9 mRNA	MMP-13 mRNA	ADAMTS-1 mRNA
Ⅰ级组	30	0.41±0.11	0.31±0.11	0.35±0.12	0.37±0.11	0.41±0.15
Ⅱ级组	32	0.37±0.25	0.38±0.12^*	0.43±0.15^*	0.35±0.10	0.39±0.14
Ⅲ级组	35	0.40±0.81	0.45±0.13^*#	0.61±0.14^*#	0.40±0.15	0.37±0.15
Ⅳ级组	33	0.35±0.12	0.56±0.21^*#△	0.87±0.23^*#△	0.39±0.13	0.42±0.17
Ⅴ级组	30	0.39±0.34	0.57±0.23^*#△	0.85±0.21^*#△	0.41±0.15	0.39±1.04
组别	ADAMTS-4 mRNA	ADAMTS-5 mRNA	IL-1α mRNA	IL-1β mRNA	IL-6 mRNA	IL-8 mRNA
Ⅰ级组	0.37±0.13	0.35±0.12	0.28±0.11	0.39±0.13	0.36±0.09	0.41±0.13
Ⅱ级组	0.56±0.21^*	0.47±0.14^*	0.54±0.13^*	0.57±0.15^*	0.35±0.11	0.39±0.12
Ⅲ级组	0.75±0.22^*#	0.67±0.17^*#	0.67±0.15^*#	0.75±0.17^*#	0.39±0.15	0.42±0.14
Ⅳ级组	0.94±0.25^*#	0.89±0.18^*#	0.87±0.14^*#△	0.97±0.16^*#△	0.41±0.13	0.40±0.11
Ⅴ级组	0.96±0.23^*#	0.91±0.20^*#	0.89±0.17^*#△	0.93±0.15^*#△	0.40±0.11	0.41±0.15

项目	MMP-3 mRNA		MMP-9 mRNA		ADAMTS-4 mRNA		ADAMTS-5 mRNA
项目	r值	P值	r值	P值	r值	P值	r值	P值
IL-1α mRNA	0.407	<0.05	0.571	<0.05	0.426	<0.05	0.577	<0.05
IL-1β mRNA	0.413	<0.05	0.522	<0.05	0.438	<0.05	0.534	<0.05

项目	MMP-3 mRNA		MMP-9 mRNA		ADAMTS-4 mRNA		ADAMTS-5 mRNA
项目	r值	P值	r值	P值	r值	P值	r值	P值
IL-1α mRNA	0.407	<0.05	0.571	<0.05	0.426	<0.05	0.577	<0.05
IL-1β mRNA	0.413	<0.05	0.522	<0.05	0.438	<0.05	0.534	<0.05