Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo

Legrand, Catherine; Ahmed, Usman; Anwar, Attia; Rajpoot, Kashif; Pasha, Sabah; Lambert, Cécile; Davidson, Rose; Clark, Ian M.; Thornalley, Paul J.; Henrotin, Yves; Rabbani, Naila

doi:10.1186/s13075-018-1636-6

Cited by 15 publications

(19 citation statements)

References 41 publications

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“…The study by Zhang WD et al identi ed two metabolic endotypes of knee osteoarthritis that differed in synovial uid concentrations of acylcarnitine and carnitine [43], which would help to unravel the pathogenesis and develop targeted therapies for OA. In a recent study, glucosepane markedly increased with age and disease progression in both a guinea pig model of knee OA and osteoarthritis in patients [44]. The association of glucosepane with aging-related OA may, for the rst time, improve early-stage OA diagnosis and prognosis.…”

Section: Discussionmentioning

confidence: 94%

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis

Luo

Samuels

Krasnokutsky

et al. 2020

Preprint

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Objective: Osteoarthritis (OA) is a disease with multiple endotypes. A hallmark of OA is loss of cartilage; however, it is evident that the rate of cartilage loss differs among patients, which may partly be attributed to differential capacity for cartilage repair. We hypothesize that a low cartilage repair endotype exists and that such endotypes are more likely to progress radiographically. The aim of this study was to examine the associations of level of cartilage formation with OA severity and radiographic OA progression. We used the blood-based marker PRO-C2, reflecting type II collagen formation, to assess levels of cartilage formation. Methods: The type II collagen propeptide PRO-C2 was measured in the serum/plasma of knee OA subjects from New York University (NYU, n=106) and a subcohort of the phase III oral salmon calcitonin (sCT) trial SMC021-2301 (SMC, n=147). The risk of radiographic medial joint space narrowing (JSN) over 24 months was compared between quartiles (very low, low, moderate, and high) of PRO-C2. Progression was defined as two-year JSN > 0.35 mm. Associations were adjusted for age, gender, BMI, race, baseline pain levels, and baseline joint space width.Results: In both the NYU and SMC cohorts, subjects with low PRO-C2 levels had greater JSN compared to subjects with high PRO-C2. The mean difference in JSN between subjects with very low and high levels of PRO-C2 was 0.65 mm (p = 0.002), corresponding to a 3.4 [1.4 – 8.6]-fold higher risk of progression. There was no significant effect of sCT treatment, compared to placebo, on JSN over two years before stratification based on baseline PRO-C2. However, there were proportionately fewer progressors in the sCT arm of the very low/low PRO-C2 group compared to the moderate/high group (chi-squared = 6.5, p = 0.011). Conclusions: Serum/plasma level of type II collagen formation, PRO-C2, may be an objective indicator of a low cartilage repair endotype, displaying radiographic progression and superior response to a proanabolic drug.

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Section: Discussionmentioning

confidence: 94%

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis

Luo

Samuels

Krasnokutsky

et al. 2020

Preprint

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“…Levels of the major glycation adduct of methylglyoxal, hydroimidazolone MG-H1, are linked to fasting and postprandial glucose exposure, insulin resistance and cardiovascular disease [12,22,39,40]. The AGE, CML, is mainly formed by oxidative degradation of FL: the CML/FL ratio in proteins is therefore a marker of oxidative stress [41]. Glucosepane is the major quantitative crosslink formed in protein glycation, formed from FL residues [42].…”

Section: Protein Ageomics and Other Modifications As Reporters Of Metmentioning

confidence: 99%

“…Glucosepane is the major quantitative crosslink formed in protein glycation, formed from FL residues [42]. It is a marker of glycemic control [43] and the major glycation adduct released from joint proteins during early-stage development of osteoarthritis [41]. Pentosidine is pentose sugar-derived AGE and intense fluorophore.…”

Section: Protein Ageomics and Other Modifications As Reporters Of Metmentioning

confidence: 99%

“…Protein glycation and oxidation adducts from dietary protein do not contribute to levels of glycation and oxidation adduct residues of protein; the latter reflecting rather rates of endogenous glycation and oxidation of protein in mainly the vascular compartment [51]. The dominance of plasma protein AGE and oxidation adducts in Algorithm-1 and the modest improvement by addition of plasma protein free adducts -which have contributions from glycated and oxidized proteins of dietary origin [22,41] -may indicate that there is limited influence of dietary glycated and oxidized proteins on the diagnosis of ASD by this blood test.…”

Section: Diagnostic Algorithm For Autism Spectrum Disorder (Asd)mentioning

confidence: 99%

“…Interestingly, hyp was a feature required only to distinguish between healthy controls and arthritis (any type); and anti-CCP antibody status was a feature required only to identify the type of arthritis. Subsequent studies of the time course of changes of protein GON free adducts in plasma of a guinea pig model of osteoarthritis showed a progressive increase of these analytes as arthritis develops and cartilage is eroded, suggesting that this effect is due to increased proteolysis of proteins of the joint as the severity of arthritis increases [41]. Glycated, oxidized and nitrated amino acids are likely better reporters of early stage arthritis development than unmodified amino acids because they are not re-incorporated into protein and hence accumulate.…”

Section: Diagnostic Algorithms For Early Detection and Typing Of Arthmentioning

confidence: 99%

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Reading patterns of proteome damage by glycation, oxidation and nitration: quantitation by stable isotopic dilution analysis LC-MS/MS

Rabbani

Thornalley

2020

Essays in Biochemistry

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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides a high sensitivity, high specificity multiplexed method for concurrent detection of adducts formed by protein glycation, oxidation and nitration, also called AGEomics. Combined with stable isotopic dilution analysis, it provides for robust quantitation of protein glycation, oxidation and nitration adduct analytes. It is the reference method for such measurements. LC-MS/MS has been used to measure glycated, oxidized and nitrated amino acids – also called glycation, oxidation and nitration free adducts, with a concurrent quantitation of the amino acid metabolome in physiological fluids. Similar adduct residues in proteins may be quantitated with prior exhaustive enzymatic hydrolysis. It has also been applied to quantitation of other post-translation modifications, such as citrullination and formation of Nε-(γ-glutamyl)lysine crosslink by transglutaminases. Application to cellular and extracellular proteins gives estimates of the steady-state levels of protein modification by glycation, oxidation and nitration, and measurement of the accumulation of glycation, oxidation and nitration adducts in cell culture medium and urinary excretion gives an indication of flux of adduct formation. Measurement of glycation, oxidation and nitration free adducts in plasma and urine provides for estimates of renal clearance of free adducts. Diagnostic potential in clinical studies has been enhanced by the combination of estimates of multiple adducts in optimized diagnostic algorithms by machine learning. Recent applications have been in early-stage detection of metabolic, vascular and renal disease, and arthritis, metabolic control and risk of developing vascular complication in diabetes, and a blood test for autism.

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AGE/Non-AGE Glycation: An Important Event in Rheumatoid Arthritis Pathophysiology

Monu,

Agnihotri,

Biswas

2021

Inflammation

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Rheumatoid arthritis (RA) is a chronic inflammatory, autoimmune disease that gradually affects the synovial membrane and joints. Many intrinsic and/or extrinsic factors are crucial in making RA pathology challenging throughout the disease. Substantial enzymatic or non-enzymatic modification of proteins driving inflammation has gained a lot of interest in recent years. Endogenously modified glycated protein influences disease development linked with AGEs/non-AGEs and is reported as a disease marker. In this review, we summarized current knowledge of the differential abundance of glycated proteins by compiling and analyzing a variety of AGE and non-AGE ligands that bind with RAGE to activate multi-faceted inflammatory and oxidative stress pathways that are pathobiologically associated with RA-fibroblast-like synoviocytes (RA-FLS). It is critical to comprehend the connection between oxidative stress and inflammation generation, mediated by glycated protein, which may bind to the receptor RAGE, activate downstream pathways, and impart immunogenicity in RA. It is worth noting that AGEs and non-AGEs ligands play a variety of functions, and their functionality is likely to be more reliant on pathogenic states and severity that may serve as biomarkers for RA. Screening and monitoring of these differentially glycated proteins, as well as their stability in circulation, in combination with established pre-clinical characteristics, may aid or predict the onset of RA.KEY WORDS: rheumatoid arthritis (RA); rheumatoid factors (RF); anti-citrullinated peptide antibodies (ACPAs); advanced glycation end-products (AGEs); glyoxal (GO); methylglyoxal (MGO); N-carboxymethyl lysine (CML); reactive oxygen species (ROS); interleukin (IL).

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Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo

Cited by 15 publications

References 41 publications

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis

A low cartilage formation and repair endotype predicts radiographic progression of symptomatic knee osteoarthritis

Reading patterns of proteome damage by glycation, oxidation and nitration: quantitation by stable isotopic dilution analysis LC-MS/MS

AGE/Non-AGE Glycation: An Important Event in Rheumatoid Arthritis Pathophysiology

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