Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages

Li, W; Du, Chigang; Wang, H; Zhang, C

doi:10.4238/2014.november.14.9

Cited by 44 publications

(39 citation statements)

References 27 publications

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“…Clinical detection of early-stage arthritis herein is potentially advantageous. Other serum markers for eOA detection have been suggested - disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, matrix metalloproteinase (MMP)-1 and MMP-3 - but sensitivity and specificity was not reported [54]. The diagnostic performance of the two-step algorithm herein improves significantly on other current candidate biomarkers proposed for early-stage arthritis [16, 55, 56].…”

Section: Discussionmentioning

confidence: 96%

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

et al. 2016

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BackgroundThere is currently no blood-based test for detection of early-stage osteoarthritis (OA) and the anti-cyclic citrullinated peptide (CCP) antibody test for rheumatoid arthritis (RA) has relatively low sensitivity for early-stage disease. Morbidity in arthritis could be markedly decreased if early-stage arthritis could be routinely detected and classified by clinical chemistry test. We hypothesised that damage to proteins of the joint by oxidation, nitration and glycation, and with signatures released in plasma as oxidized, nitrated and glycated amino acids may facilitate early-stage diagnosis and typing of arthritis.MethodsPatients with knee joint early-stage and advanced OA and RA or other inflammatory joint disease (non-RA) and healthy subjects with good skeletal health were recruited for the study (n = 225). Plasma/serum and synovial fluid was analysed for oxidized, nitrated and glycated proteins and amino acids by quantitative liquid chromatography-tandem mass spectrometry. Data-driven machine learning methods were employed to explore diagnostic utility of the measurements for detection and classifying early-stage OA and RA, non-RA and good skeletal health with training set and independent test set cohorts.ResultsGlycated, oxidized and nitrated proteins and amino acids were detected in synovial fluid and plasma of arthritic patients with characteristic patterns found in early and advanced OA and RA, and non-RA, with respect to healthy controls. In early-stage disease, two algorithms for consecutive use in diagnosis were developed: (1) disease versus healthy control, and (2) classification as OA, RA and non-RA. The algorithms featured 10 damaged amino acids in plasma, hydroxyproline and anti-CCP antibody status. Sensitivities/specificities were: (1) good skeletal health, 0.92/0.91; (2) early-stage OA, 0.92/0.90; early-stage RA, 0.80/0.78; and non-RA, 0.70/0.65 (training set). These were confirmed in independent test set validation. Damaged amino acids increased further in severe and advanced OA and RA.ConclusionsOxidized, nitrated and glycated amino acids combined with hydroxyproline and anti-CCP antibody status provided a plasma-based biochemical test of relatively high sensitivity and specificity for early-stage diagnosis and typing of arthritic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1154-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 96%

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

et al. 2016

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“…ADAMTS4 has been put forward as a biochemical marker for the recognition of early OA in many in vivo and in vitro experimental studies. However, there have been no examinations of the influence of the ADAMTS4 gene on OA etiology in the literature (Gendron et al, 2007;Naito et al, 2007;Xue et al, 2013;Li et al, 2014). We investigated the relationship between the rs4233367 G/T and rs11807350 G/T gene polymorphisms and primary knee OA.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in ADAMTS4 and ADAMTS5 are not linked to susceptibility to knee osteoarthritis in the Turkish population

et al. 2016

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ABSTRACT. Considering the functions of aggrecanase-1 (ADAMTS4) and -2 (ADAMTS5), which are thought to be the two major enzymes responsible for the destruction of aggrecans in arthritic diseases, we investigated whether important polymorphisms in the ADAMTS4 and ADAMTS5 genes affect osteoarthritis (OA) susceptibility. Our study took place in Mugla, Turkey. Ninety-five cases were recruited following OA diagnosis (72 women and 23 men), and 80 individuals without any symptoms or radiographic signs of OA (56 women and 24 men) were chosen as healthy controls. After obtaining DNA from patients and control subjects, ADAMTS4 and ADAMTS5 genotypes were determined using the ABI Prism StepOnePlus Real-Time system. In addition, we categorized patients based on OA grade. There were no significant differences in the genotype distributions of the four polymorphisms between the groups (P > 0.05). Moreover, ADAMTS4 and ADAMTS5 allele frequencies did not differ between OA and control participants (P > 0.05). These findings suggest that the ADAMTS4 (rs4233367 and rs11807350) and ADAMTS5 (rs226794 and rs2830585) variants examined may not contribute to susceptibility to knee OA in the Turkish population. Other gene polymorphisms should be assessed in order to explain variations in OA susceptibility.

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“…S1A; Supplementary Data are available online at www.liebertpub.com/tea), consistent with previous reports of OAC expression profiles. 8,54,55 At the protein level, when compared to NCs, OACs produced significantly higher levels of MMP-9 and certain inflammatory cytokines (IL-1b, IL-8, MCP-1, VEGF, and IL-13) (Supplementary Fig. S1B).…”

Section: Initial Chondrocyte and Macrophage Phenotype Before Coculturementioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Increased serum ADAMTS-4 in knee osteoarthritis: a potential indicator for the diagnosis of osteoarthritis in early stages

Cited by 44 publications

References 27 publications

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

Protein oxidation, nitration and glycation biomarkers for early-stage diagnosis of osteoarthritis of the knee and typing and progression of arthritic disease

Polymorphisms in ADAMTS4 and ADAMTS5 are not linked to susceptibility to knee osteoarthritis in the Turkish population

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

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