Skip to main content
Top
Published in: European Journal of Medical Research 1/2024

Open Access 01-12-2024 | Biomarkers | Research

Diagnostic value of serum COMP and ADAMTS7 for intervertebral disc degeneration

Authors: Jing-Yu Ding, Xu Yan, Ren-Jie Zhang, Hua-Qing Zhang, Liang Kang, Chong-Yu Jia, Rick F. Thorne, Xiao-Ying Liu , Cai-Liang Shen

Published in: European Journal of Medical Research | Issue 1/2024

Login to get access

Abstract

Objective

Intervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship.

Methods

IVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1–4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I–V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses.

Results

COMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD.

Conclusions

Increases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391(10137):2356–67.CrossRefPubMed Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet. 2018;391(10137):2356–67.CrossRefPubMed
2.
go back to reference Wilson Zingg R, Kendall R. Obesity, vascular disease, and lumbar disk degeneration: associations of comorbidities in low back pain. PM R. 2017;9(4):398–402.CrossRefPubMed Wilson Zingg R, Kendall R. Obesity, vascular disease, and lumbar disk degeneration: associations of comorbidities in low back pain. PM R. 2017;9(4):398–402.CrossRefPubMed
3.
go back to reference Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: epidemiology and therapy. Osteoarthritis Cartilage. 2020;28(3):242–8.CrossRefPubMed Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: epidemiology and therapy. Osteoarthritis Cartilage. 2020;28(3):242–8.CrossRefPubMed
4.
go back to reference Liu Y, Du J, Peng P, et al. Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy. Bioact Mater. 2021;6(1):146–57.PubMed Liu Y, Du J, Peng P, et al. Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy. Bioact Mater. 2021;6(1):146–57.PubMed
6.
go back to reference Frapin L, Clouet J, Delplace V, et al. Lessons learned from intervertebral disc pathophysiology to guide rational design of sequential delivery systems for therapeutic biological factors. Adv Drug Deliv Rev. 2019;149–150:49–71.CrossRefPubMed Frapin L, Clouet J, Delplace V, et al. Lessons learned from intervertebral disc pathophysiology to guide rational design of sequential delivery systems for therapeutic biological factors. Adv Drug Deliv Rev. 2019;149–150:49–71.CrossRefPubMed
7.
go back to reference Zhang W, Li G, Luo R, et al. Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis. Exp Mol Med. 2022;54(2):129–42.CrossRefPubMedPubMedCentral Zhang W, Li G, Luo R, et al. Cytosolic escape of mitochondrial DNA triggers cGAS-STING-NLRP3 axis-dependent nucleus pulposus cell pyroptosis. Exp Mol Med. 2022;54(2):129–42.CrossRefPubMedPubMedCentral
8.
9.
go back to reference Ntoumou E, Tzetis M, Braoudaki M, et al. Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes. Clin Epigenetics. 2017;9:127.CrossRefPubMedPubMedCentral Ntoumou E, Tzetis M, Braoudaki M, et al. Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes. Clin Epigenetics. 2017;9:127.CrossRefPubMedPubMedCentral
11.
go back to reference Sampara P, Banala RR, Vemuri SK, et al. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review. Gene Ther. 2018;25(2):67–82.CrossRefPubMed Sampara P, Banala RR, Vemuri SK, et al. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review. Gene Ther. 2018;25(2):67–82.CrossRefPubMed
12.
go back to reference Li W, Wang P, Zhang Z, et al. MiR-184 regulates proliferation in nucleus pulposus cells by targeting gas1. World Neurosurg. 2017;97:710-15.e1.CrossRefPubMed Li W, Wang P, Zhang Z, et al. MiR-184 regulates proliferation in nucleus pulposus cells by targeting gas1. World Neurosurg. 2017;97:710-15.e1.CrossRefPubMed
13.
go back to reference Hamilton-Bennett SE, Behr S. Clinical presentation, magnetic resonance imaging features, and outcome in 6 cats with lumbar degenerative intervertebral disc extrusion treated with hemilaminectomy. Vet Surg. 2019;48(4):556–62.CrossRefPubMed Hamilton-Bennett SE, Behr S. Clinical presentation, magnetic resonance imaging features, and outcome in 6 cats with lumbar degenerative intervertebral disc extrusion treated with hemilaminectomy. Vet Surg. 2019;48(4):556–62.CrossRefPubMed
14.
go back to reference Kreiner DS, Hwang SW, Easa JE, et al. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J. 2014;14(1):180–91.CrossRefPubMed Kreiner DS, Hwang SW, Easa JE, et al. An evidence-based clinical guideline for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Spine J. 2014;14(1):180–91.CrossRefPubMed
15.
go back to reference Zeckser J, Wolff M, Tucker J, et al. Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells Int. 2016;2016:3908389.CrossRefPubMedPubMedCentral Zeckser J, Wolff M, Tucker J, et al. Multipotent mesenchymal stem cell treatment for discogenic low back pain and disc degeneration. Stem Cells Int. 2016;2016:3908389.CrossRefPubMedPubMedCentral
16.
go back to reference Heo JH, Kim CH, Chung CK, et al. Quantity of disc removal and radiological outcomes of percutaneous endoscopic lumbar discectomy. Pain Physician. 2017;20(5):E737–46.PubMed Heo JH, Kim CH, Chung CK, et al. Quantity of disc removal and radiological outcomes of percutaneous endoscopic lumbar discectomy. Pain Physician. 2017;20(5):E737–46.PubMed
17.
go back to reference Biomarkers and surrogate endpoints. preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.CrossRef Biomarkers and surrogate endpoints. preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.CrossRef
18.
go back to reference Bai W, Hao Q, Zhang Z, et al. Identification of a novel inflammation-related gene signature for predicting inflammatory breast cancer survival. Genome Instab & Dis. 2023;4(3):154–75.CrossRef Bai W, Hao Q, Zhang Z, et al. Identification of a novel inflammation-related gene signature for predicting inflammatory breast cancer survival. Genome Instab & Dis. 2023;4(3):154–75.CrossRef
19.
go back to reference Goode AP, Marshall SW, Kraus VB, et al. Association between serum and urine biomarkers and lumbar spine individual radiographic features: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage. 2012;20(11):1286–93.CrossRefPubMedPubMedCentral Goode AP, Marshall SW, Kraus VB, et al. Association between serum and urine biomarkers and lumbar spine individual radiographic features: the Johnston County Osteoarthritis Project. Osteoarthritis Cartilage. 2012;20(11):1286–93.CrossRefPubMedPubMedCentral
21.
go back to reference Er ZJ, Yin CF, Wang WJ, et al. Serum CXCL12/SDF-1 level is positively related with lumbar intervertebral disc degeneration and clinical severity. Innate Immun. 2020;26(5):341–50.CrossRefPubMed Er ZJ, Yin CF, Wang WJ, et al. Serum CXCL12/SDF-1 level is positively related with lumbar intervertebral disc degeneration and clinical severity. Innate Immun. 2020;26(5):341–50.CrossRefPubMed
22.
go back to reference Guo W, Zhang B, Li Y, et al. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration. Mol Med Rep. 2017;16(6):8665–72.CrossRefPubMedPubMedCentral Guo W, Zhang B, Li Y, et al. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration. Mol Med Rep. 2017;16(6):8665–72.CrossRefPubMedPubMedCentral
23.
go back to reference Zhang Y, Hu Y, Wang W, et al. Current progress in the endogenous repair of intervertebral disk degeneration based on progenitor cells. Front Bioeng Biotechnol. 2020;8: 629088.CrossRefPubMed Zhang Y, Hu Y, Wang W, et al. Current progress in the endogenous repair of intervertebral disk degeneration based on progenitor cells. Front Bioeng Biotechnol. 2020;8: 629088.CrossRefPubMed
24.
go back to reference Verma P, Dalal K. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. J Orthop Res. 2013;31(7):999–1006.CrossRefPubMed Verma P, Dalal K. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. J Orthop Res. 2013;31(7):999–1006.CrossRefPubMed
25.
go back to reference Rosenberg K, Olsson H, Mörgelin M, et al. Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen. J Biol Chem. 1998;273(32):20397–403.CrossRefPubMed Rosenberg K, Olsson H, Mörgelin M, et al. Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen. J Biol Chem. 1998;273(32):20397–403.CrossRefPubMed
26.
go back to reference Holden P, Meadows RS, Chapman KL, et al. Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family. J Biol Chem. 2001;276(8):6046–55.CrossRefPubMed Holden P, Meadows RS, Chapman KL, et al. Cartilage oligomeric matrix protein interacts with type IX collagen, and disruptions to these interactions identify a pathogenetic mechanism in a bone dysplasia family. J Biol Chem. 2001;276(8):6046–55.CrossRefPubMed
27.
go back to reference Vilím V, Olejárová M, Machácek S, et al. Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage. 2002;10(9):707–13.CrossRefPubMed Vilím V, Olejárová M, Machácek S, et al. Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis. Osteoarthritis Cartilage. 2002;10(9):707–13.CrossRefPubMed
28.
29.
go back to reference Vos LM, Kuijer R, Huddleston Slater JJ, et al. Alteration of cartilage degeneration and inflammation markers in temporomandibular joint osteoarthritis occurs proportionally. J Oral Maxillofac Surg. 2013;71(10):1659–64.CrossRefPubMed Vos LM, Kuijer R, Huddleston Slater JJ, et al. Alteration of cartilage degeneration and inflammation markers in temporomandibular joint osteoarthritis occurs proportionally. J Oral Maxillofac Surg. 2013;71(10):1659–64.CrossRefPubMed
30.
go back to reference Halász K, Kassner A, Mörgelin M, et al. COMP acts as a catalyst in collagen fibrillogenesis. J Biol Chem. 2007;282(43):31166–73.CrossRefPubMed Halász K, Kassner A, Mörgelin M, et al. COMP acts as a catalyst in collagen fibrillogenesis. J Biol Chem. 2007;282(43):31166–73.CrossRefPubMed
31.
go back to reference Qi DD, Liu ZH, Wu DS, et al. A Study on COMP and CTX-II as Molecular markers for the diagnosis of intervertebral disc degeneration. Biomed Res Int. 2021;2021:3371091.CrossRefPubMedPubMedCentral Qi DD, Liu ZH, Wu DS, et al. A Study on COMP and CTX-II as Molecular markers for the diagnosis of intervertebral disc degeneration. Biomed Res Int. 2021;2021:3371091.CrossRefPubMedPubMedCentral
32.
go back to reference Guo F, Lai Y, Tian Q, et al. Granulin-epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein. Arthritis Rheum. 2010;62(7):2023–36.CrossRefPubMedPubMedCentral Guo F, Lai Y, Tian Q, et al. Granulin-epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein. Arthritis Rheum. 2010;62(7):2023–36.CrossRefPubMedPubMedCentral
33.
go back to reference Luan Y, Kong L, Howell DR, et al. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthritis Cartilage. 2008;16(11):1413–20.CrossRefPubMedPubMedCentral Luan Y, Kong L, Howell DR, et al. Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin. Osteoarthritis Cartilage. 2008;16(11):1413–20.CrossRefPubMedPubMedCentral
34.
go back to reference Yu H, Zhu Y. Expression of ADAMTS-7 and ADAMTS-12 in the nucleus pulposus during degeneration of rat caudal intervetebral disc. J Vet Med Sci. 2012;74(1):9–15.CrossRefPubMed Yu H, Zhu Y. Expression of ADAMTS-7 and ADAMTS-12 in the nucleus pulposus during degeneration of rat caudal intervetebral disc. J Vet Med Sci. 2012;74(1):9–15.CrossRefPubMed
36.
go back to reference Miyamoto T, Muneta T, Tabuchi T, et al. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther. 2010;12(6):R206.CrossRefPubMedPubMedCentral Miyamoto T, Muneta T, Tabuchi T, et al. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinase-related genes in nucleus pulposus cells in rabbits. Arthritis Res Ther. 2010;12(6):R206.CrossRefPubMedPubMedCentral
37.
go back to reference Deval E, Gasull X, Noël J, et al. Acid-sensing ion channels (ASICs): pharmacology and implication in pain. Pharmacol Ther. 2010;128(3):549–58.CrossRefPubMed Deval E, Gasull X, Noël J, et al. Acid-sensing ion channels (ASICs): pharmacology and implication in pain. Pharmacol Ther. 2010;128(3):549–58.CrossRefPubMed
38.
go back to reference Akinmade A, Oginni LM, Adegbehingbe OO, et al. Serum cartilage oligomeric matrix protein as a biomarker for predicting development and progression of knee osteoarthritis. Int Orthop. 2021;45(3):551–7.CrossRefPubMed Akinmade A, Oginni LM, Adegbehingbe OO, et al. Serum cartilage oligomeric matrix protein as a biomarker for predicting development and progression of knee osteoarthritis. Int Orthop. 2021;45(3):551–7.CrossRefPubMed
39.
go back to reference Karamouzian S, Eskandary H, Faramarzee M, et al. Frequency of lumbar intervertebral disc calcification and angiogenesis, and their correlation with clinical, surgical, and magnetic resonance imaging findings. Spine. 2010;35(8):881–6.CrossRefPubMed Karamouzian S, Eskandary H, Faramarzee M, et al. Frequency of lumbar intervertebral disc calcification and angiogenesis, and their correlation with clinical, surgical, and magnetic resonance imaging findings. Spine. 2010;35(8):881–6.CrossRefPubMed
40.
go back to reference Zhang S, Wang P, Hu B, et al. Inhibiting heat shock protein 90 attenuates nucleus pulposus fibrosis and pathologic angiogenesis induced by macrophages via down-regulating cell migration-inducing protein. Am J Pathol. 2023;193(7):960–76.CrossRefPubMed Zhang S, Wang P, Hu B, et al. Inhibiting heat shock protein 90 attenuates nucleus pulposus fibrosis and pathologic angiogenesis induced by macrophages via down-regulating cell migration-inducing protein. Am J Pathol. 2023;193(7):960–76.CrossRefPubMed
41.
go back to reference Caron MMJ, Janssen MPF, Peeters L, et al. Aggrecan and COMP improve periosteal chondrogenesis by delaying chondrocyte hypertrophic maturation. Front Bioeng Biotechnol. 2020;8:1036.CrossRefPubMedPubMedCentral Caron MMJ, Janssen MPF, Peeters L, et al. Aggrecan and COMP improve periosteal chondrogenesis by delaying chondrocyte hypertrophic maturation. Front Bioeng Biotechnol. 2020;8:1036.CrossRefPubMedPubMedCentral
Metadata
Title
Diagnostic value of serum COMP and ADAMTS7 for intervertebral disc degeneration
Authors
Jing-Yu Ding
Xu Yan
Ren-Jie Zhang
Hua-Qing Zhang
Liang Kang
Chong-Yu Jia
Rick F. Thorne
Xiao-Ying Liu 
Cai-Liang Shen
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Biomarkers
Published in
European Journal of Medical Research / Issue 1/2024
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-024-01784-w

Other articles of this Issue 1/2024

European Journal of Medical Research 1/2024 Go to the issue