Consequences of metabolic and oxidative modifications of cartilage tissue

Hardin, John A.; Cobelli, Neil J.; Santambrogio, Laura

doi:10.1038/nrrheum.2015.70

Cited by 47 publications

(44 citation statements)

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“…Oxidative damage, nitration and glycation of cartilage is associated with misfolding and aggregation of the proteoglycan–collagen network surrounding chondrocytes and matrix degradation. These damaging modifications are thought to compromise structural integrity and viscoelasticity of cartilage, impairing its ability to sustain mechanical pressures and joint function [11]. …”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…A previous study by Fields reported that endplate degeneration such as endplate sclerosis, increased endplate thickness and decreased endplate porosity can be observed in type 2 diabetic rat . Many studies have demonstrated that the apoptosis of cartilage endplate (CEP) cells plays an important role in CEP degeneration . However, to date, few studies have investigated the effect of diabetes on the CEP, especially at the cellular level.…”

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confidence: 99%

High glucose‐induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells

Jiang

Zeng

et al. 2018

Journal Orthopaedic Research

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Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high-glucose medium (10% FBS + 0.1 M glucose or 10% FBS + 0.2 M glucose, experimental conditions) for 1 or 3 days. In addition, CEP cells were treated with 0.2 M glucose for 3 days in the presence or absence of alpha-lipoic acid (ALA, 0.15 M). Flow cytometry was performed to identify and quantify the degree of apoptosis. The expression of reactive oxygen species (ROS) was assessed by flow cytometry, and mitochondrial damage (mitochondrial membrane potential) was assessed by fluorescence microscopy. Furthermore, the expression levels of cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, and cytochrome c were evaluated by Western blotting. High glucose significantly increased apoptosis and ROS accumulation in CEP cells in a dose- and time-dependent manner. Meanwhile, a disrupted mitochondrial membrane potential was detected in rat CEP cells cultured in the two high glucose concentrations. Incubating in high glucose enhanced the expression levels of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but decreased the level of the anti-apoptotic protein Bcl-2. ALA inhibited the expression of cleaved caspase-3, cleaved caspase-9, Bax, and cytochrome c but enhanced the expression of Bcl-2. ALA also prevented disruption of the mitochondrial membrane potential in CEP cells. This study demonstrates that high glucose-induced excessive reactive oxygen species promote mitochondrial damage, thus causing apoptosis in rat CEP cells in a dose- and time-dependent manner. ALA could prevent mitochondrial damage and apoptosis caused by high glucose in CEP cells. The results suggest that appropriate blood glucose control may be the key to preventing IDD in diabetic patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2476-2483, 2018.

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“…This was performed as previous reports have stated that in papain-induced models, this part is the most severely affected area that exhibits little or no regenerative alterations (26). Cartilage thickness was determined from zones 1 to 3 (the surface layer to the radial zone) (27). …”

Section: Methodsmentioning

confidence: 99%

A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells

Delgado‐Enciso

García²,

Hernández

et al. 2017

Mol Med Report

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Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease-modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX-9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage-stimulating protein receptor (osteoclastogenic factor) expression. The intra-articular application of BIOF2 in the animal models significantly increased cartilage thickness from 12 to 31% at 28 days, compared with articular cartilage treated with saline solution. The articular area and number of chondrocytes additionally increased significantly, maintaining an unaltered chondrocyte/mm2 proportion. Evaluation of the histological architecture additionally displayed a decrease in the grade of articular damage in the groups treated with BIOF2. In conclusion, BIOF2 has proven to be effective for treating OA in animal models, most likely due to SOX9 overexpression in articular cells.

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Consequences of metabolic and oxidative modifications of cartilage tissue

Cited by 47 publications

References 100 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

High glucose‐induced excessive reactive oxygen species promote apoptosis through mitochondrial damage in rat cartilage endplate cells

A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells

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