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Published in: Journal of Orthopaedic Surgery and Research 1/2016

Open Access 01-12-2016 | Research article

Combined detection of serum CTX-II and COMP concentrations in osteoarthritis model rabbits: an effective technique for early diagnosis and estimation of disease severity

Authors: Bin Bai, Yanqin Li

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2016

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Abstract

Background

Early diagnosis of osteoarthritis (OA) is difficult. Cartilage oligomeric matrix protein (COMP) and crosslinked C-telopeptides of type II collagen (CTX-II) are two markers which can potentially predict the destruction of articular cartilage of early OA. To comprehensively evaluate the diagnosis value of serum COMP and CTX-II markers in OA, the longitudinal and combined measurement of serum COMP and CTX-II were performed at different stages of pathological process of OA in adult rabbits with OA, compared with the sham-operated rabbits.

Methods

Thirty-six adult white rabbits were randomly divided into two groups, the OA group and the control group (n = 18 per group). OA models were established by anterior cruciate ligament transection. Sham operations were performed in the control group. Before the surgery and at weeks 2, 4, 6, 8, 10, and 12 after surgery, serum CTX-II and COMP concentrations were detected using sandwich-ELISA in all rabbits. Three rabbits in each group were killed at weeks 2, 4, 6, 8, 10, and 12 after surgery, and femoral condyle specimens were collected. Histological changes in articular cartilage were evaluated according to the Mankin scoring criteria.

Results

At each time point, the Mankin scores and serum concentrations of CTX-II and COMP were significantly higher in the OA group than in the control group. In addition, in the OA group, there was a significant relationship between the CTX-II and COMP concentrations and the Mankin score.

Conclusions

Early dynamic combined detection of serum CTX-II and COMP concentrations is effective for early OA diagnosis and evaluation of OA severity.
Literature
1.
go back to reference Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Prac Res Clin Rheumatol. 2014;28(1):5–15.CrossRef Johnson VL, Hunter DJ. The epidemiology of osteoarthritis. Best Prac Res Clin Rheumatol. 2014;28(1):5–15.CrossRef
2.
go back to reference Losina E, Weinstein AM, Reichmann WM, Burbine SA, Solomon DH, Daigle ME, Rome BN, Chen SP, Hunter DJ, Suter LG, Jordan JM, Katz JN. Life time risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res (Hoboken). 2013;65(5):703–11.CrossRef Losina E, Weinstein AM, Reichmann WM, Burbine SA, Solomon DH, Daigle ME, Rome BN, Chen SP, Hunter DJ, Suter LG, Jordan JM, Katz JN. Life time risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res (Hoboken). 2013;65(5):703–11.CrossRef
3.
go back to reference Sulzbacher I. Osteoarthritis: histology and pathogenesis. Wien Med Wochenschr. 2013;163(9-10):212–9.CrossRefPubMed Sulzbacher I. Osteoarthritis: histology and pathogenesis. Wien Med Wochenschr. 2013;163(9-10):212–9.CrossRefPubMed
4.
go back to reference Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ. Osteoarthritis. Lancet. 2015;386(9991):376–87.CrossRefPubMed Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ. Osteoarthritis. Lancet. 2015;386(9991):376–87.CrossRefPubMed
5.
go back to reference Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377(9783):2115–26.CrossRefPubMed Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377(9783):2115–26.CrossRefPubMed
6.
go back to reference Carr AJ, Robertsson O, Graves S, Price AJ, Arden NK, Judge A, Beard DJ. Knee replacement. Lancet. 2012;379(9823):1331–40.CrossRefPubMed Carr AJ, Robertsson O, Graves S, Price AJ, Arden NK, Judge A, Beard DJ. Knee replacement. Lancet. 2012;379(9823):1331–40.CrossRefPubMed
7.
go back to reference Blanco FJ. Osteoarthritis year in review 2014: we need more biochemical biomarkers in qualification phase. Osteoarthritis Cartilage. 2014;22(12):2025–32.CrossRefPubMed Blanco FJ. Osteoarthritis year in review 2014: we need more biochemical biomarkers in qualification phase. Osteoarthritis Cartilage. 2014;22(12):2025–32.CrossRefPubMed
8.
go back to reference Hosnijeh FS, Runhaar J, van Meurs JB, Bierma-Zeinstra SM. Biomarkers for osteoarthritis: can they be used for risk assessment? A systematic review. Maturitas. 2015;82(1):36–49.CrossRefPubMed Hosnijeh FS, Runhaar J, van Meurs JB, Bierma-Zeinstra SM. Biomarkers for osteoarthritis: can they be used for risk assessment? A systematic review. Maturitas. 2015;82(1):36–49.CrossRefPubMed
9.
go back to reference Van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthritis Cartilage. 2010;18(5):605–12.CrossRefPubMed Van Spil WE, DeGroot J, Lems WF, Oostveen JC, Lafeber FP. Serum and urinary biochemical markers for knee and hip-osteoarthritis: a systematic review applying the consensus BIPED criteria. Osteoarthritis Cartilage. 2010;18(5):605–12.CrossRefPubMed
10.
go back to reference Lotz M, Martel-Pelletier J, Christiansen C, Brandi ML, Bruyère O, Chapurlat R, Collette J, Cooper C, Giacovelli G, Kanis JA, Karsdal MA, Kraus V, Lems WF, Meulenbelt I, Pelletier JP, Raynauld JP, Reiter-Niesert S, Rizzoli R, Sandell LJ, Van Spil WE, Reginster JY. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis. 2013;72(11):1756–63.CrossRefPubMedPubMedCentral Lotz M, Martel-Pelletier J, Christiansen C, Brandi ML, Bruyère O, Chapurlat R, Collette J, Cooper C, Giacovelli G, Kanis JA, Karsdal MA, Kraus V, Lems WF, Meulenbelt I, Pelletier JP, Raynauld JP, Reiter-Niesert S, Rizzoli R, Sandell LJ, Van Spil WE, Reginster JY. Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis. 2013;72(11):1756–63.CrossRefPubMedPubMedCentral
11.
go back to reference Kumm J, Tamm A, Lintrop M, Tamm A. The value of cartilage biomarkers in progressive knee osteoarthritis: cross-sectional and 6-year follow-up study in middle-aged subjects. Rheumatol Int. 2013;33(4):903–11.CrossRefPubMed Kumm J, Tamm A, Lintrop M, Tamm A. The value of cartilage biomarkers in progressive knee osteoarthritis: cross-sectional and 6-year follow-up study in middle-aged subjects. Rheumatol Int. 2013;33(4):903–11.CrossRefPubMed
12.
go back to reference Zuo H, Jiang L, Qu N, Wang J, Cui X, Yao W. The biomarkers changes in serum and the correlation with quantitative MRI markers by histopathologic evaluation of the cartilage in surgically-induced osteoarthritis rabbit model. PLoSOne. 2015;10(4):e0124717.CrossRef Zuo H, Jiang L, Qu N, Wang J, Cui X, Yao W. The biomarkers changes in serum and the correlation with quantitative MRI markers by histopathologic evaluation of the cartilage in surgically-induced osteoarthritis rabbit model. PLoSOne. 2015;10(4):e0124717.CrossRef
13.
go back to reference Charni-Ben Tabassi N, Desmarais S, Bay-Jensen AC, Delaissé JM, Percival MD, Garnero P. The type II collagen fragments helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation. Osteoarthritis Cartilage. 2008;16(10):1183–91.CrossRefPubMed Charni-Ben Tabassi N, Desmarais S, Bay-Jensen AC, Delaissé JM, Percival MD, Garnero P. The type II collagen fragments helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation. Osteoarthritis Cartilage. 2008;16(10):1183–91.CrossRefPubMed
14.
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
15.
go back to reference Clark AG, Jordan JM, Vilim V, Renner JB, Dragomir AD, Luta G, Kraus VB. Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. Arthritis Rheum. 1999;42(11):2356–64.CrossRefPubMed Clark AG, Jordan JM, Vilim V, Renner JB, Dragomir AD, Luta G, Kraus VB. Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. Arthritis Rheum. 1999;42(11):2356–64.CrossRefPubMed
16.
go back to reference Yoshioka M, Coutts RD, Amiel D, Hacker SA. Characterization of a model of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage. 1996;4(2):87–98.CrossRefPubMed Yoshioka M, Coutts RD, Amiel D, Hacker SA. Characterization of a model of osteoarthritis in the rabbit knee. Osteoarthritis Cartilage. 1996;4(2):87–98.CrossRefPubMed
17.
go back to reference Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971;53(3):523–37.CrossRefPubMed Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971;53(3):523–37.CrossRefPubMed
18.
go back to reference Dunn S, Kolomytkin OV, Marino AA. Pathophysiology of osteoarthritis: evidence against the viscoelastic theory. Pathobiology. 2009;76(6):322–8.CrossRefPubMed Dunn S, Kolomytkin OV, Marino AA. Pathophysiology of osteoarthritis: evidence against the viscoelastic theory. Pathobiology. 2009;76(6):322–8.CrossRefPubMed
19.
go back to reference Tang X, Zhou Z, Shen B, Yang J, Kang P, Li J, Crook N, Li Q, Min L, Pei F. Serum levels of TNF-α, IL-1β, COMP, and CTX-II in patients with Kashin-Beck disease in Sichuan. China Rheumatol Int. 2012;32(11):3503–9.CrossRefPubMed Tang X, Zhou Z, Shen B, Yang J, Kang P, Li J, Crook N, Li Q, Min L, Pei F. Serum levels of TNF-α, IL-1β, COMP, and CTX-II in patients with Kashin-Beck disease in Sichuan. China Rheumatol Int. 2012;32(11):3503–9.CrossRefPubMed
20.
go back to reference Duclos ME, Roualdes O, Cararo R, Rousseau JC, Roger T, Hartmann DJ. Significance of the serum CTX-II level in an osteoarthritis animal model: a 5-month longitudinal study. Osteoarthritis Cartilage. 2010;18(11):1467–76.CrossRefPubMed Duclos ME, Roualdes O, Cararo R, Rousseau JC, Roger T, Hartmann DJ. Significance of the serum CTX-II level in an osteoarthritis animal model: a 5-month longitudinal study. Osteoarthritis Cartilage. 2010;18(11):1467–76.CrossRefPubMed
21.
go back to reference Tanishi N, Yamagiwa H, Hayami T, Mera H, Koga Y, Omori G, Endo N. Relationship between radiological knee osteoarthritis and biochemical markers of cartilage and bone degradation (urine CTX-II and NTX-I): the Matsudai Knee Osteoarthritis Survey. J Bone Miner Metab. 2009;27(5):605–12.CrossRefPubMed Tanishi N, Yamagiwa H, Hayami T, Mera H, Koga Y, Omori G, Endo N. Relationship between radiological knee osteoarthritis and biochemical markers of cartilage and bone degradation (urine CTX-II and NTX-I): the Matsudai Knee Osteoarthritis Survey. J Bone Miner Metab. 2009;27(5):605–12.CrossRefPubMed
22.
go back to reference Jordan KM, Syddall HE, Garnero P, Gineyts E, Dennison EM, Sayer AA, Delmas PD, Cooper C, Arden NK. Urinary CTX-II and glucosyl-galactosyl-pyridinoline are associated with the presence and severity of radiographic knee osteoarthritis in men. Ann Rheum Dis. 2006;65(7):871–7.CrossRefPubMedPubMedCentral Jordan KM, Syddall HE, Garnero P, Gineyts E, Dennison EM, Sayer AA, Delmas PD, Cooper C, Arden NK. Urinary CTX-II and glucosyl-galactosyl-pyridinoline are associated with the presence and severity of radiographic knee osteoarthritis in men. Ann Rheum Dis. 2006;65(7):871–7.CrossRefPubMedPubMedCentral
23.
go back to reference Fernandes FA, Pucinelli ML, da Silva NP, Feldman D. Serum cartilage oligomeric matrix protein (COMP) levels in knee osteoarthritis in a Brazilian population: clinical and radiological correlation. Scand J Rheumatol. 2007;36(3):211–5.CrossRefPubMed Fernandes FA, Pucinelli ML, da Silva NP, Feldman D. Serum cartilage oligomeric matrix protein (COMP) levels in knee osteoarthritis in a Brazilian population: clinical and radiological correlation. Scand J Rheumatol. 2007;36(3):211–5.CrossRefPubMed
24.
go back to reference El-Arman MM, El-Fayoumi G, El-Shal E, El-Boghdady I, El-Ghaweet A. Aggrecan and cartilage oligomeric matrix protein in serum and synovial fluid of patients with knee osteoarthritis. HSS J. 2010;6(2):171–6.CrossRefPubMedPubMedCentral El-Arman MM, El-Fayoumi G, El-Shal E, El-Boghdady I, El-Ghaweet A. Aggrecan and cartilage oligomeric matrix protein in serum and synovial fluid of patients with knee osteoarthritis. HSS J. 2010;6(2):171–6.CrossRefPubMedPubMedCentral
25.
go back to reference Lai Y, Yu XP, Zhang Y, Tian Q, Song H, Mucignat MT, Perris R, Samuels J, Krasnokutsky S, Attur M, Greenberg JD, Abramson SB, Di Cesare PE, Liu CJ. Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. Osteoarthritis Cartilage. 2012;20(8):854–62.CrossRefPubMedPubMedCentral Lai Y, Yu XP, Zhang Y, Tian Q, Song H, Mucignat MT, Perris R, Samuels J, Krasnokutsky S, Attur M, Greenberg JD, Abramson SB, Di Cesare PE, Liu CJ. Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. Osteoarthritis Cartilage. 2012;20(8):854–62.CrossRefPubMedPubMedCentral
26.
go back to reference Dodge GR, Hawkins D, Boesler E, Sakai L, Jimenez SA. Production of cartilage oligomeric matrix protein (COMP) by cultured human dermal and synovial fibroblasts. Osteoarthritis Cartilage. 1998;6(6):435–40.CrossRefPubMed Dodge GR, Hawkins D, Boesler E, Sakai L, Jimenez SA. Production of cartilage oligomeric matrix protein (COMP) by cultured human dermal and synovial fibroblasts. Osteoarthritis Cartilage. 1998;6(6):435–40.CrossRefPubMed
Metadata
Title
Combined detection of serum CTX-II and COMP concentrations in osteoarthritis model rabbits: an effective technique for early diagnosis and estimation of disease severity
Authors
Bin Bai
Yanqin Li
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2016
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-016-0483-x

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