M. Deberg

University of Liège, Luik, Walloon Region, Belgium

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Publications (49)199.62 Total impact

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    ABSTRACT: Background Coll2-1 and Coll2-1NO2are biomarkers of cartilage degradation. Coll2-1 is a peptide of 9 amino acids (108HRGYPGLDG116), located in the helical part of type II collagen molecule. Coll2-1NO2 [HRGY(NO2)PGLDG], the nitrated form of Coll2-1, is a marker of cartilage degradation related to inflammation. Objectives To evaluate the predictive value of Coll2-1 and Coll2-1NO2 for radiographic knee osteoarthritis progression. Methods Coll2-1 and Coll2-1NO2 were measured in 178 plasma (sColl2-1 and sColl2-1NO2) and urine (uColl2-1 and uColl2-1NO2) samples from obese women with moderate unilateral radiographic knee OA. Changes in joint space width (JSW) in the medial tibiofemoral compartment were obtained from fluoroscopically assisted semi-flexed AP radiographs performed at baseline and 30 months. Coll2-1 and Coll2-1NO2 were measured at baseline and after 6, 12, 18, 24 and 30 months. Patients showing a decrease of JSW≥0.5 mm over 30 months follow-up were considered as radiographic progressors. The descriptive and predictive values of plasma and urinary biomarkers were determined by univariate and multivariate data analysis at several time points. Throughout these analyses, we have been mainly interested in the feasibility and design of really predictive solutions. To assess the predictive power of the markers, resampling strategies were set up where a randomly drawn sample of patients was used to build a predictive model (a regularized logistic regression), while the patients not used to build this model were used to validate its predictive performance. This scheme was repeated several hundreds of time. Results The 178 women were, on average, 53.88 years old and had a BMI of 36.14kg/m2. The minimum JSW at inclusion was 3.94 mm (3.17 mm- 4.55 mm) [median (interquartile range)]. After 30 months, the minimum JSN was -0.53 mm (-0.91 mm- -0.15 mm). Among this population, 86 patients were radiographic nonprogressors while 92 patients were radiographic progressors. When the discrimination power of a single marker at a single time point was studied, only the difference between M18 and M0 of uColl2-1 tended to reach the signification (p= 0.052, with p-values corrected for multiple testing). As far as predictive power in terms of AUC is concerned, similar solutions based on only one out of the two biomarkers have been built. The best AUC obtained were for uColl2-1NO2 at M0 and uColl2-1 at M0 and M6 and M0 and M18. When combining several biomarkers at several time-points, equivalent solutions have been built for M0&M6, M0&M18 but also for M0 only. The results obtained are summarized in Table 1 Conclusions Some interesting results were obtained with plasma but all the best results were obtained in urine. Out of the 2 biomarkers, Coll2-1 provided the best performance when taken at baseline. M6 and M18 time-points in urine could be considered as equivalently predictive. Nevertheless, a combination of both biomarkers in urine provided a gain in predictive performance (AUC up to 0.70). Disclosure of Interest Y. Henrotin Shareholder of: Artialis, Consultant for: Artialis, V. Kraus: None Declared, J. Huebner: None Declared, T. Helleputte: None Declared, M. Deberg Employee of: Artialis
    No preview · Article · Jan 2014 · Annals of the Rheumatic Diseases
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    ABSTRACT: To determine the influence of marathon on the serum levels of two markers of cartilage degradation, Coll2-1 and its nitrated form, Coll2-1NO2, and of a marker of neutrophils activation, the myeloperoxidase (MPO). Coll2-1, Coll2-1NO2, total and active MPO were measured in 98 marathon runners without joint pain and with an average age of 47 years. Sera were taken at rest right before the departure and within 30 min after the marathon. The subjects were submitted to a questionnaire concerning their physical activity and their life style. The levels of Coll2-1, Coll2-1NO2 and active MPO were not affected by age, body mass index, sex or performance. The levels of total MPO were higher in female than in male (p < 0.05), but were not affected by the other parameters. After the marathon, Coll2-1 and Coll2-1NO2 concentrations were slightly but systematically decreased. The total and active MPO concentrations were increased by 2 to 3-fold in comparison to the pre-marathon values (p < 0.001 for total and active MPO). The active MPO/total MPO ratio was significantly enhanced after the marathon (p < 0.001). The variation of total MPO during the marathon was negatively correlated with the training time per week (r = −0.34; p = 0.009). The serum levels of Coll2-1 and Coll2-1NO2 were slightly decreased by marathon, indicating that intensive running could reduce cartilage catabolism. Furthermore, Coll2-1NO2 was not correlated with the total and active MPO indicating that Coll2-1 nitration did not result of a systemic oxidative phenomenon but reflects local changes.
    Full-text · Article · Dec 2013 · SpringerPlus
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    ABSTRACT: To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2-1 and Coll2-1 NO(2) in knee osteoarthritic patients after viscosupplementation (VS). Fifty-one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra-articular injections of 2 ml of hyaluronic acid (Hylan GF-20) and were followed for 3 months. Walking pain was evaluated and serum samples were taken at each visit. Coll2-1 and Coll2-1 NO(2) were measured in the serum using specific immunoassays. Variations over time of each parameter and predictive factor of response were studied. Forty-five patients were analyzed. The serum concentrations of Coll2-1 and Coll2-1 NO(2) were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS. Its effect was ever more pronounced in patients with KL III/IV. The serum concentration of Coll2-1 was significantly lower at baseline in responders than in non-responders. This study suggests a rapid slowdown of type II collagen degradation and joint inflammation after VS with Hylan G-20 and gives additional information for the validation of accurate biomarkers for OA. The serum level of Coll2-1 appeared to be a predictive factor for response to treatment. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
    Full-text · Article · Jun 2013 · Journal of Orthopaedic Research
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    ABSTRACT: This study was undertaken to identify new biomarkers of osteoarthritis (OA) by proteomics analysis and to develop specific immunoassays to detect and quantify them. Proteomics analysis was performed in urine samples from 10 women (mean±SD age 76.0±5.0 years) undergoing knee replacement surgery due to severe OA and 5 healthy women (mean±SD age 25.6±2.6 years). Protein content was analyzed by 2-dimensional differential gel electrophoresis. Protein spots that exhibited an OA:control abundance ratio of ≥1.5 were identified by mass spectrometry. Specific enzyme-linked immunosorbent assays were developed and validated in serum obtained from 236 healthy subjects ages 20-64 years and from 76 patients with severe radiologic knee OA (mean±SD age 68.8±11.9 years). Immunohistochemical analysis was performed on articular cartilage from tibial plateaus. Thirteen proteins within spots that were significantly modified between groups were identified. Two peptides of fibulin 3, named Fib3-1 and Fib3-2, were of particular interest. Two antisera directed against these peptides were used to develop immunoassays. Compared with age-matched healthy subjects, median levels of serum Fib3-1 and Fib3-2 were elevated in OA patients (54.6 pM versus 85.1 pM [P<0.0001] and 144.4 pM versus 191.4 pM [P<0.0001], respectively). Using area under the receiver operating characteristic curve analysis, we demonstrated that Fib3-1 and Fib3-2 levels discriminate between OA and normal populations. Immunostaining revealed the presence of Fib3-1 and Fib3-2 in chondrocytes and in the extracellular matrix of the superficial layer of the fibrillated cartilage. Our findings indicate that Fib3-1 and Fib3-2 are potential biochemical markers for the diagnosis of OA.
    Full-text · Article · Jul 2012 · Arthritis & Rheumatology
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    Full-text · Article · Apr 2012 · Osteoarthritis and Cartilage
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    ABSTRACT: PURPOSE: The aim of this study was to measure in canine experimental osteoarthritis (OA) the serum concentrations of Coll2-1 and Coll2-1NO(2), two specific biomarkers of OA, and myeloperoxidase (MPO) and correlate those with macroscopic and histological parameters. METHODS: Anterior cruciate ligament transection was performed surgically on the right knee of 16 adult crossbred dogs. Coll2-1, Coll2-1NO(2) and MPO were measured in the dog serum by specific immunoassays at baseline and every 2 weeks during 8 weeks. After 8 weeks, the macroscopic evaluation and cartilage histology of the knee were performed. RESULTS: After ACL transection, the concentration of the 3 biomarkers increased significantly over time. Coll2-1 levels were found to be correlated with the global macroscopic score, the size of cartilage lesions and the change in histological cartilage structure. Correlations were also found between Coll2-1 NO(2) and the size of osteophytes. CONCLUSIONS: These results showed that the serum levels of Coll2-1 and Coll2-1 NO(2) in OA dogs paralleled the development of the disease. Interestingly, both Coll2-1NO(2) and MPO were increased in OA dogs, highlighting the role of inflammation in this OA model. This study confirmed the usefulness of Coll2-1 and Coll2-1NO(2) as OA biomarkers.
    Full-text · Article · Mar 2012 · Osteoarthritis and Cartilage
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    ABSTRACT: Erosive osteoarthritis of the hand (EHOA) is thought to be an aggressive variant of hand osteoarthritis (HOA) characterised by prominent local inflammation and radiographic aspects of bone erosions in interphalangeal (IP) joints. However, rare studies have until now investigated the value of biomarkers in these patients. Thus, we determined Coll2-1, a marker of type II collagen denaturation, its nitrated form (Coll2-1NO2) and myeloperoxidase (MPO) levels in serum of patients with EHOA vs non-EHOA and subsequently evaluated their relationships with disease indices of severity and activity.
    Full-text · Article · Mar 2012 · Osteoarthritis and Cartilage
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    Myriam Gharbi · Michelle Deberg · Yves Henrotin
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    ABSTRACT: After the genomic era, proteomic corresponds to a wide variety of techniques that study the protein content of cells, tissue, or organism and that allow the isolation of protein of interest. It offers the choice between gel-based and gel-free methods or shotgun proteomics. Applications of proteomic technology may concern three principal objectives in several biomedical or clinical domains of research as in osteoarthritis: (i) to understand the physiopathology or underlying mechanisms leading to a disease or associated with a particular model, (ii), to find disease-specific biomarker, and (iii) to identify new therapeutic targets. This review aimed at gathering most of the data regarding the proteomic techniques and their applications to osteoarthritis research. It also reported technical limitations and solutions, as for example for sample preparation. Proteomics open wide perspectives in biochemical research but many technical matters still remain to be solved.
    Full-text · Article · Dec 2011 · Frontiers in Physiology
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    Full-text · Article · Sep 2011 · Osteoarthritis and Cartilage
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    Full-text · Article · Sep 2011 · Osteoarthritis and Cartilage
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    ABSTRACT: The measurement of biomarkers that reflect cartilage breakdown is a powerful tool for investigating joint damage caused by disease or injury. Particularly in cases of osteochondrosis, synovial concentrations of these biomarkers may reveal the presence of osteoarthritic changes. Coll2-1, Coll2-1 NO2 and myeloperoxidase have recently been introduced in equine osteoarticular research but comparison between the concentrations of these markers in OCD affected and healthy joints has not been made. Therefore, this study aimed at reporting the synovial concentrations of these biomarkers in joints affected with osteochondral fragments in the tarsocrural joint compared to unaffected joints. Myeloperoxidase and Coll2-1NO2 revealed to have similar levels between affected joints and controls. However, in contrast to previous studies using C2C the present study demonstrated that synovial levels of Coll2-1 were significantly elevated in tarsocrural joints affected with osteochondrosis. Thus, Coll2-1 may be an earlier marker of cartilage degeneration than other cartilage degradation markers that have been previously used in equine medicine.
    No preview · Article · Jun 2011 · Veterinary Research Communications
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    ABSTRACT: To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA). Serum levels of metalloproteinase-1 (MMP-1), MMP-3, MMP-13, myeloperoxidase and cathepsin K were analysed in 73 patients with OA and 77 healthy controls carrying the haplogroups J, U and H, by ELISA. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from grade 0 to grade IV. Non-parametric and multiple regression analyses were performed to test the effects of clinical variables, including gender, age, smoking status, diagnosis, haplogroups and radiological K/L grade on serum levels of these enzymes. A significant influence of the haplogroups on the serum levels of MMP-3 and MMP-13 was detected (p=0.027 and p=0.035, respectively). Patients with OA with haplogroup H showed higher serum levels of MMP-3 than healthy controls. Serum levels of MMP-13 were significantly higher in patients with OA (p<0.001), and carriers of the haplogroup J showed lower levels than H carriers. Besides, levels of MMP-13 were proportionally higher in radiological groups B (K/L grade II and III) and C (K/L grade IV) than in group A (K/L grade 0 and I) (p=0.005). This study shows that haplogroups have a significant influence on serum levels of MMP-3 and MMP-13. The influence of the haplogroups on serum levels of MMP-3 is clearly dependent on the diagnosis, whereas the influence of the haplogroups on serum levels of MMP-13 is independent of diagnosis.
    No preview · Article · Dec 2010 · Annals of the rheumatic diseases

  • No preview · Article · Oct 2010 · Osteoarthritis and Cartilage
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    Full-text · Article · Oct 2010 · Osteoarthritis and Cartilage
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    ABSTRACT: To determine the effects of iron depletion on serum levels of joint biomarkers and on joint symptoms in patients with hereditary haemochromatosis (HH). Levels of biomarkers were measured in 18 patients with HH at the time of diagnosis and after iron depletion. The markers were type II collagen degradation (Coll2-1) and its nitrated form (Coll2-1NO(2)), type II procollagen synthesis (CPII), MPO, COMP and HA. For each patient, demographic data were collected and the global joint pain (visual analogue scale) was assessed before and after iron depletion by phlebotomy. A total of 18 patients [10 males; mean (s.d.) age 48 (11) years] were homozygous for the C282Y mutation. No patient had liver dysfunction. Ferritin level before iron removal was 627.5 (range 133-3276) microg/l, and duration of the iron depletion phase was 295 (70-670) days. Serum levels of both Coll2-1 and CPII were significantly increased from diagnosis after iron depletion: 80.1 (55.6-113.5) vs 96.0 (48.8-136.3) nM (P = 0.004) and 731.4 (374.2-1012.3) vs 812.8 (535.8-1165.6) ng/ml (P = 0.03), respectively. Levels of other biomarkers were not modified by iron depletion. Ferritin level, which at baseline was correlated with body iron store (r = 0.63; P = 0.008), was significantly correlated with HA level measured before iron depletion (r = 0.60; P = 0.01). Global joint pain was not correlated with ferritin concentration and did not significantly decrease after iron depletion: 43 (19-73) vs 36 (16-67) mm (P = 0.07). In patients with HH, cartilage homoeostasis is modified by iron excess and an increase in type II collagen turnover occurs after excess iron removal.
    Full-text · Article · Apr 2010 · Rheumatology (Oxford, England)
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    ABSTRACT: Collagens are major constituents of connective tissues in the animal kingdom. During aging and inflammatory-related diseases, the collagen network undergoes oxidation that leads to structural and biochemical alterations within the collagen molecule. Collagen oxidation appears to be a key determinant of aging and a critical physiopathologic mechanism of numerous diseases. Further, the detection of oxidized-collagen peptides seems to be a promising approach for the diagnosis and the prognosis of inflammatory diseases. This chapter reviews the structural and biochemical changes to collagen induced by reactive oxygen and nitrogen species and discusses recent data on the use of collagen-derived biomarkers for measuring oxidative damage.
    No preview · Article · Dec 2009 · Advances in clinical chemistry
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    ABSTRACT: To analyse the influence of mitochondrial DNA (mtDNA) haplogroups on serum levels of molecular biomarkers in patients with osteoarthritis (OA). Serum levels of molecular biomarkers of cartilage metabolism (collagen type II markers: C-terminal neoepitope generated by the collagenase-mediated cleavage of collagen type II triple helix (C2C), collagen type II (Coll2-1, and its nitrated form, Coll2-1NO(2)), procollagen type II (CPII)), synovial metabolism (hyaluronic acid (HA)) and cartilage and synovial turnover (cartilage glycoprotein 39 (YKL-40)) were analysed in 73 patients with OA and 77 healthy controls using ELISAs. All participants had been previously genotyped for the mtDNA haplogroups J, U and H. Non-parametric and multivariate analysis were performed to test the effects of the clinical variables, including gender, age, smoking status, diagnosis, mtDNA haplogroups and radiological Kellgren and Lawrence (K/L) grade on the serum levels of the molecular markers. Non-parametric analysis found increased serum levels of HA in patients with OA, while the values for C2C and the C2C/CPII ratio were significantly higher in the healthy controls. A multiple regression analysis showed a relationship between the mtDNA haplogroups and serum levels of the typical collagen type II markers. Carriers of the mtDNA haplogroup H had higher levels while carriers of the mtDNA haplogroup J showed lower levels. Statistically significant interactions between mtDNA haplogroups and diagnosis and between mtDNA haplogroups and radiological K/L grade in the serum levels of molecular markers were also found. A new role for mtDNA haplogroups emerges from this work. The results suggest that the mtDNA haplogroups interact significantly with the serum levels of OA-related molecular markers, suggesting the possibility of their use as a complementary assay with these molecular markers.
    No preview · Article · Nov 2009 · Annals of the rheumatic diseases
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    ABSTRACT: A major barrier inhibiting the discovery of structural modifying agents for osteoarthritis (OA) is an incomplete understanding of early disease events. Herein, we investigated the time course of collagen II cleavage and fibril disruption in the well-validated Hartley guinea pig model of spontaneous OA of the knee. Knee joints of 46 male Hartley guinea pigs were analyzed at 3 weeks, 2, 4, 7, 10, 12, and 18 months of age for histological severity of OA, cartilage collagen fibril disruption by semi-quantitative polarized light microscopy, and expression of type II collagen degradation biomarkers, 9A4 and Coll2-1, by immunohistochemistry. In addition, serum biomarkers specific for collagen II degradation, CTX-II, C2C, and Coll2-1 were quantified. Collagen fibril disruption and expression of the collagenase-generated cleavage neoepitope, 9A4, were observed as early as 2 months of age, despite the appearance of histological OA at 4 months of age. Only serum Coll2-1 increased coincident with the early disruption of the collagen fibril between 3 weeks and 7 months, in contrast to serum C2C, which did not change significantly or correlate with histological severity. Inversely, CTX-II declined dramatically from 3 weeks to 4 months and remaining low thereafter, coincident with growth plate turnover. Collagenase cleavage and disruption of the type II collagen network are early OA disease events in this model, preceding histological evidence of proteoglycan loss. The markedly different serum profiles of collagen II-related biomarkers during the early stages of disease development suggest compartmental segregation and temporal regulation of collagen degrading enzymes.
    Full-text · Article · Oct 2009 · Osteoarthritis and Cartilage
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    Full-text · Article · Sep 2009 · Osteoarthritis and Cartilage
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    Full-text · Article · Sep 2009 · Osteoarthritis and Cartilage

Publication Stats

889 Citations
199.62 Total Impact Points

Institutions

  • 2005-2012
    • University of Liège
      • Faculty of Veterinary Medicine
      Luik, Walloon Region, Belgium
    • Centre Hospitalier Universitaire de Liège
      Luik, Walloon Region, Belgium