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See detailGene expression pattern of synovial cells from inflammatory and normal areas of osteoarthritis synovial membrane.
Lambert, Cécile ULg; Dubuc, Jean-Emile; Montell, Eulalia et al

in Arthritis and Rheumatism (2014), sous presse

Objective: The aim of this study was to compare the gene expression pattern of synovial cells from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same ... [more ▼]

Objective: The aim of this study was to compare the gene expression pattern of synovial cells from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same osteoarthritis (OA) patient. Methods: Synovial tissues were obtained from 12 knee OA patients at the time of total knee replacement. The inflammatory status of the synovial membrane was characterized according to macroscopic criteria and sorted as N/R and I. Biopsies were cultured separately for 7 days. Microarray gene expression profiling between N/R and I areas was performed. Western blot and immunohistochemistry confirmed the identified genes that were differentially expressed. Results: 896 differentially expressed genes between N/R and I zones were identified. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling and angiogenesis. In the inflammatory network, TREM1 and S100A9 were strongly up-regulated. MMP-3 and -9, cathepsin H and S were significantly up-regulated in the cartilage catabolism pathway, whereas the most up-regulated anabolism enzyme was HAS1. Wnt-5A and LRP5 were up-regulated whereas FZD2 and DKK3 were down-regulated in the Wnt signaling. Finally, STC1, a protein involved in angiogenesis was identified as the most up-regulated gene in I zones compared to N/R zones. Conclusion: This study is the first to identify different expression pattern between two areas of the synovial membrane in the same patient. These differences concern several key pathways involved in OA pathogenesis. This analysis also provides information regarding new genes and proteins as potential targets for the future therapeutic. (c) 2013 American College of Rheumatology. [less ▲]

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See detailEFFECTS OF CHONDROITIN SULFATE ON THE GENE EXPRESSION PROFILE IN THE INFLAMED SYNOVIAL MEMBRANE
Lambert, Cécile ULg; Dubuc, Jean-Emile; Montell, E et al

Conference (2013, November 23)

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See detailEFFECTS OF CHONDROITIN SULFATE ON THE GENE EXPRESSION PROFILE IN INTERLEUKIN-1Β STIMULATED SYNOVIAL FIBROBLAST CELLS CULTURES
Lambert, Cécile ULg; Dubuc, Jean-Emile; Montell, E et al

Conference (2013, November 23)

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See detailProtective effect of a new biomaterial against the development of experimental osteoarthritis lesions in rabbit: a pilot study evaluating the intra-articular injection of alginate-chitosan beads dispersed in an hydrogel.
Oprenyeszk, Frédéric ULg; Chausson, Mickael; Maquet, Véronique et al

in Osteoarthritis and Cartilage (2013), 21(8), 1099-1107

Objective: This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in an hydrogel (H) derived from chitosan on the development of ... [more ▼]

Objective: This study aimed to evaluate the structural benefit of a new biomaterial composed of alginate-chitosan (AC) beads dispersed in an hydrogel (H) derived from chitosan on the development of osteoarthritis (OA) in rabbit. Design: OA was induced by the surgical transection of the anterior cruciate ligament in rabbits. Animals received a single intra-articular injection (900 μl) of AC beads in H hydrogel, H hydrogel alone or saline one week after surgery. OA development was followed by X-rays. Blood samples were collected throughout the study to measure biological markers (PGE2 and CRP). Macroscopic observation and histological evaluation of articular cartilage and synovial membrane were performed 6 weeks after surgery. Results: AC beads in H hydrogel prevented from the development of OA based on the reduction of the Kellgren & Lawrence (K&L) score. It also significantly reduced the histological score of cartilage lesion severity. This effect was homogenous on every joint compartment. It was due to a significant effect on cartilage structure and cellularity scores. The injection of AC beads in H hydrogel also tended to reduce the synovial membrane inflammation. No significant variation of biological markers was noted. Conclusions: The present pilot study provides interesting and promising results for the use of AC beads in H hydrogel in animal. It indeed prevented the development of OA cartilage lesions without inflammatory signs. The potencies of this biomaterial to protect OA joint should be further documented. It could then represent a new alternative for viscosupplementation in human OA management. [less ▲]

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See detailEffects of chondroitin sulfate on the gene expression profile in IL-1β stimulated synovial fibroblast cells cultures
Lambert, Cécile ULg; Dubuc, Jean-Emile; Montell, E. et al

in Osteoarthritis and Cartilage (2013, April), 21(Supplement April 2013),

Purpose: Chondroitin sulfate (CS) is one the most used molecules in the management of OA. In this study, we performed a microarray analysis and identified a differential expression profile between control ... [more ▼]

Purpose: Chondroitin sulfate (CS) is one the most used molecules in the management of OA. In this study, we performed a microarray analysis and identified a differential expression profile between control and IL-1β stimulated synovial fibroblast cells cultures. In a second step, we investigated the effects of CS on this gene expression profile. Methods: OA synovial specimens were obtained from 12 patients undergoing knee replacement. At the surgery time, the synovial membrane was dissected. Synovial fibroblast cells (SFC) were enzymatically isolated and used after four passages (P4). SFC were pre-treated 1 hour with highly purified bovine CS (200 µg/ml, Bioibérica S.A., Barcelona, Spain) before treatment with IL-1β (1 ng/ml) for 24 hours. Total RNA was extracted using the RNeasy Mini Kit. RNA purity and quality were evaluated using the Experion RNA StdSens Analysis kit (Bio-rad Laboratories). Gene expression profiling was performed using Illumina’s multi-sample format Human HT-12 BeadChip (Illumina Inc.). Differential analysis was performed with the BRB array tools software. Class comparison test between control (Ctl) and interleukin (IL)-1β conditions, Ctl and Ctl/CS and IL-1β and IL-1β/CS conditions was based on paired t-test where Ctl and IL-1β, Ctl and Ctl/CS and IL-1β and IL-1β/CS were paired for each patient. The biological relevance of up- and down-regulated genes was analyses with Ingenuity Pathways Analysis (Ingenuity® Systems). Probes with a p-value below 0.001 were chosen and classified as up- or down-regulated ones. Results: 3308 genes were identified as differentially expressed genes between Ctl and IL-1β conditions. We observed a differential profile of expression of major pathways involved in OA pathogenesis. The key identified pathways were related to inflammation, complement cascade, angiogenesis, cartilage catabolism and anabolism and Wnt signaling. In the inflammatory network, the most upregulated cytokines were IL-8 and IL-6 with a fold change of 156.25 and 58.8 respectively. We also identified several chemokines, enzymes and metallothioneins (MTs). Complement factor B (CFB) and complement component 3 (C3) are two factors upregulated in the inflammatory complement cascade. We also identified some genes implicated in the angiogenesis pathway. The most upregulated was Stanniocalcin 1 (STC1) with a fold change of 9.09. The differential expression of intermediates involved in both cartilage anabolism and catabolism was revealed by the IL-1β stimulation, showing an imbalance in favour of catabolism. MMP-3 was largely upregulated (fold change of 62.5). Wnt 5A and low density lipoprotein receptor-related protein (LRP8) were significantly upregulated while frizzled homolog 2 (FZD2) and dickkopf homolog 3 (DKK3) were downregulated in the Wnt signaling pathway. We next performed a class comparison test between Ctl and Ctl/CS in one hand and IL-1β and IL-1β/CS on the other hand. 660 genes were identified as differentially expressed between Ctl and Ctl/CS conditions while 241 genes were identified between IL-1β and IL-1β/CS. Among them, our attention was focused on two genes upregulated in the presence of CS: lysyl oxidase-like 4 (LOXL4) and claudin 11 (CDLN11), two genes that negatively regulate cell invasion. Conclusions: We here evidenced in synovial fibroblast cells the modulation of gene expression following IL-1β stimulation. We also demonstrated the modulatory effects of CS on gene expression and isolated several CS-modulated genes of interest such as LOXL4 and CDLN11, which could constitute new mechanisms of action of the molecule and contribute to explain the symptomatic efficacy of CS in the treatment of OA. [less ▲]

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See detailThe intra-articular injection of a new chitosan biomaterial prevents the progression of osteoarthritis in ACLT rabbit model
Oprenyeszk, Frédéric ULg; Chausson, Mickael; Maquet, Véronique et al

in Osteoarthritis and Cartilage (2013, April), 21(Supplement April 2013), 69

Purpose To evaluate the effects of a single intra-articular injection of a new biomaterial consisting in a mix of alginate-chitosan (AC) beads and a viscous thermogelling chitosan-based (H) hydrogel on ... [more ▼]

Purpose To evaluate the effects of a single intra-articular injection of a new biomaterial consisting in a mix of alginate-chitosan (AC) beads and a viscous thermogelling chitosan-based (H) hydrogel on cartilage lesion in osteoarthritis (OA) rabbit model. These effects were compared to those obtained with the intra-articular injection of either chitosan-based (H) hydrogel without the AC bead or saline solution. Methods OA was surgically induced by the transection of the anterior cruciate ligament (ACLT) in HYLA albino rabbits. One week after surgery, animals were randomly divided into 3 groups: group I (n=7): mix of AC beads and H hydrogel; group II (n=7): H hydrogel alone; group III (n=7): saline solution (control). The treatments (900 µl) were injected intra-articularly. X-rays from the right knee were performed before surgery, at the time of injection and at sacrifice. The standard radiographs were acquired in extension and scored by the Kellgren and Lawrence (K&L) scale. After 6 weeks, animals were euthanized and the right joint was dissected. The macroscopic evaluation of cartilage from femoral condyles and tibial plateaus stained with India ink was done. Histological sections stained with Safranine-O/fast green from bearing areas of each compartment were evaluated according to the OARSI histological score. Briefly, the evaluation considered: staining of the cartilage matrix (0-6), cartilage structure (0-11), chondrocyte density (0-4) and cluster formation (0-3), where 0 represented a normal situation and 24 points the maximum severity score. Blood samples were collected the day of injection and prior the sacrifice. Prostaglandin E2 (PGE2) and C-reactive protein (CRP) were measured in serum using immunoassays. Results The X-rays analysis showed a significant decrease (p <0.05) of the K&L score in group I (AC beads and H hydrogel; 1.5 ± 0.2) compared with group II (H hydrogel; 2.2 ± 0.5) and group III (saline solution; 3.0 ± 0.4). The size and the severity of the macroscopic OA cartilage lesion tended to decrease in group I compared to the other groups. The histological global score that refers to all compartments of the knee joint was significantly decreased in group I (11.0 ± 0.7) compared to group II (14.4 ± 0.6, p <0.01) and group III (14.8 ± 0.6, p <0.001). No significant variation of PGE2 and CRP serum levels were observed in each after 6 weeks follow-up whatever the treatment injected. Conclusions This study showed that a biphasic hydrogel composed by AC beads and H hydrogel prevented OA in rabbit with ACL transection. This effect was not observed with the hydrogel alone, suggesting that AC beads play a role in joint protection. The preventive effect was observed in all joint compartments indicating a global protective effect of this new viscosupplementation. [less ▲]

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See detailAlginate-chitosan hydrogel beads decrease inflammatory and anabolic mediators produced by human chondrocytes
Oprenyeszk, Frédéric ULg; Sanchez, Christelle ULg; Dubuc, Jean-Emile et al

Poster (2012, September 17)

Introduction Osteoarthritis (OA) is the most prevalent arthritic disease. It is characterized by the degradation of articular cartilage accompanied by the inflammation of the synovial membrane and ... [more ▼]

Introduction Osteoarthritis (OA) is the most prevalent arthritic disease. It is characterized by the degradation of articular cartilage accompanied by the inflammation of the synovial membrane and sclerosis of subchondral bone. OA produces pain and loss of joint function. Today, there is no treatment to cure OA or to delay effectively its progression. Current treatments are mainly based on alleviation of painful symptoms but are unable to restore the cartilage. The development of new scaffold for tissue engineering is a promising approach. Herein, we report the effects of alginate-chitosan hydrogel (AC) beads on the metabolism of chondrocytes. Materials and Methods Human chondrocytes were isolated from OA cartilage and cultured either in AC beads or in alginate (A) beads. AC beads were prepared using chitosan (KiOmedine-CsU ultra-pure chitosan from KitoZyme, Herstal, Belgium) and alginate. The two polymer solutions were prepared separately before being mixed together. Cells were added to the polymer mixture and the cell-containing beads prepared by precipitation in a calcium chloride solution. The chondrocytes embedded in the beads were then cultured in a well defined culture medium for up to 28 days. Cell viability was determined by quantifying the release of lactate deshydrogenase (LDH) in the culture supernatant. Interleukin (IL)-6 and -8, prostaglandin E2 (PGE2), matrix metalloprotease (MMP)-3 and aggrecan were measured by specific ELISA. Finally, nitric oxide (NO) was measured by the Griess reaction. Results Histological analysis of AC beads showed chondrocytes in contact with chitosan trabeculae that were homogeneously distributed in the alginate matrix. LDH level remained below the limit of detection over the culture duration suggesting that AC had no cytotoxic effect. By comparison with culture in A beads, chondrocytes in AC beads produced significantly higher amounts of aggrecan but lowered the levels of MMP-3, NO, IL-6, IL-8 and PGE2. Discussion The contact between cells and AC beads components led us to hypothesize that chitosan has beneficial effects such as anti-inflammatory, anti-catabolic and stimulating effects on cartilage matrix components. Conclusion These particular effects indicate that AC beads are potentially new carriers for cell transplantation, particularly to repair cartilage defects. They could be further developed under various formulations, such as microbeads in combination with hydrogel for efficient viscossuplementation. [less ▲]

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See detailAn original methodology to study the synovial tissue in OA patient
Lambert, Cécile ULg; Dubuc, Jean-Emile; Henrotin, Yves ULg

Poster (2012, April 19)

Purpose: Synovial membrane plays a key role in osteoarthritis (OA) pathophysiology, contributing to both patient symptoms and disease progression. Using an original methodology comparing normal/reactive ... [more ▼]

Purpose: Synovial membrane plays a key role in osteoarthritis (OA) pathophysiology, contributing to both patient symptoms and disease progression. Using an original methodology comparing normal/reactive (N/R) and inflammatory (I) synovial membrane areas from the same OA patient, we investigated the crosstalk between inflammation and angiogenesis. We also analyzed the gene expression pattern of synovial cells from these different areas and identified differentially regulated pathways. Methods: Synovial cells (SC) were isolated from OA synovial specimens obtained from patients undergoing knee replacement. The inflammatory status of the synovial membrane was characterized by the surgeon according the macroscopic criteria including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. At the surgery time, the synovial membrane was dissected and the biopsies from N/R and I areas cultured separately for a period of 7 days. Inflammatory and angiogenic mediators were evaluated in the culture supernatant by immunoassays (ELISA) or visualized by immunohistochemistry. Gene expression profiling between N/R and I areas was performed using Illumina’s multi-sample format human HT-12 BeadChip (Illumina Inc.). Results: Immunohistochemistry showed an increase of lymphocyte infiltration, vascular density and VEGF expression in I compared N/R synovial biopsies. Synovial cells from I areas produced more IL-6, IL-8 and VEGF but less TSP-1 than cells isolated from N/R synovial biopsies. By microarray analysis, 896 differentially expressed genes between N/R and I zones were identified. Among them, 576 genes were upregulated (I/NR > 1.5) and 320 downregulated (I/NR  0.75). A significant number of the top ranking differentially expressed genes were identified as inflammatory, cartilage metabolism, Wnt or angiogenic pathways. Conclusion: In this study, we have demonstrated the pro-inflammatory and pro-angiogeneic status of I area of the OA synovial membrane. Using a unique culture system, this study is the first to identify different expression pattern between two areas of the synovial membrane in the same OA patient. This original methodology could be further used to go deeper into the knowledge of the role of synovial membrane in OA. Possibilities for valorization: This analysis provided interesting information regarding new potent intermediates that could be potential new targets for the diagnosis or treatment of OA. [less ▲]

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See detailExpression of specific pathways in the inflamed synovial membrane of osteoarthritis patient: Identification of new potential key intermediates
Lambert, Cécile ULg; Dubuc, Jean-Emile; Hennuy, Benoît ULg et al

in Osteoarthritis and Cartilage (2012, April), 20(Supplement 1), 56

Purpose: Synovitis is a key factor in osteoarthritis (OA) pathophysiology, contributing to both patient symptoms and disease progression. In this study, using an original methodology comparing normal ... [more ▼]

Purpose: Synovitis is a key factor in osteoarthritis (OA) pathophysiology, contributing to both patient symptoms and disease progression. In this study, using an original methodology comparing normal/reactive (N/R) and inflammatory (I) synovial membranes zones, we investigated the gene expression profiles of synovial cells from these areas and identified differentially regulated pathways. Methods: Synovial cells (SC) were isolated from OA synovial specimens obtained from 12 patients undergoing knee replacement. The inflammatory status of the synovial membrane was characterized by the surgeon according to macroscopic criteria including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. At the surgery time, the synovial membrane was dissected and biopsies from N/R and I areas cultured separately for a period of 7 days. Total RNA was extracted using the RNeasy Mini Kit. RNA purity and quality were evaluated using the Experion RNA StdSens Analysis kit (Bio-rad Laboratories). Gene expression profiling between N/R and I areas was performed using Illumina’s multi-sample format Human HT-12 BeadChip (Illumina Inc.). Differential analysis was performed with the BRB array tools software. Class Comparison test between N/R and I areas was based on paired t-test where N/R and I were paired for each patient. The biological relevance of up- and down-regulated genes was analyses with Ingenuity Pathways Analysis (Ingenuity® Systems). Western blot was performed to confirm certain intermediate expression. Results: From among 47000 probes, 17500 were filtered out. Probes with a p-value below than 0.005 were chosen and classified as up- or down-regulated ones. By this way, 896 differentially expressed genes between N/R and I zones were identified. Among these, 576 genes were upregulated (I/NR > 1.5) and 320 downregulated (I/NR < 0.75). With Ingenuity Pathways Analysis, a significant number of the top ranking differentially expressed genes were identified as inflammatory, Wnt and angiogenic pathways. Interleukin (IL)-6 and -8, chemokines (CXCL1, CXCL2, CXCL5, CXCL6, CXCL16) and arachidonate 5-lipoxygenase (ALOX5) were identified as the most upregulated in I zones in the inflammatory pathway. Interestingly, the alarmin S100A9 was found strongly upregulated in this pathway. Wnt5A and LRP (Low density lipoprotein receptor-related protein) 5 were upregulated whereas FZD (Frizzled homolog) 2 and DKK (dickkopf homolog) 3 were downregulated in the Wnt signaling pathway. Finally, stanniocalcin (STC)-1, an intermediate in angiogenesis was identified as the most upregulated gene in I zones compared to N/R zones. This difference of expression was confirmed at the protein level. Conclusions: Using a unique culture system, this study is the first to identify different expression pattern between two areas of synovial membrane from the same OA patient. These differences concern several key pathways involved in OA pathogenesis, i.e. inflammation, Wnt and angiogenesis. This analysis also provided interesting information regarding new potent intermediates as S100A9 and STC-1. They could be potential targets for chondroitin sulfate, one of the most used molecules in the management of OA. New experiments are being perfomed at the moment to elucidate the potential effect of this molecule on these specific differentially expressed genes in the same culture system. [less ▲]

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See detailExpression of specific pathways in the inflamed synovial membrane of osteoarthritis patient: Identification of new potential key intermediates
Lambert, Cécile ULg; Dubuc, Jean-Emile; Hennuy, Benoît ULg et al

in Osteoarthritis and Cartilage (2012, April), 20(Supplement 1), 56

Purpose: Synovitis is a key factor in osteoarthritis (OA) pathophysiology, contributing to both patient symptoms and disease progression. In this study, using an original methodology comparing normal ... [more ▼]

Purpose: Synovitis is a key factor in osteoarthritis (OA) pathophysiology, contributing to both patient symptoms and disease progression. In this study, using an original methodology comparing normal/reactive (N/R) and inflammatory (I) synovial membranes zones, we investigated the gene expression profiles of synovial cells from these areas and identified differentially regulated pathways. Methods: Synovial cells (SC) were isolated from OA synovial specimens obtained from 12 patients undergoing knee replacement. The inflammatory status of the synovial membrane was characterized by the surgeon according to macroscopic criteria including the synovial vascularization, the villi formation and the hypertrophic aspect of the tissue. At the surgery time, the synovial membrane was dissected and biopsies from N/R and I areas cultured separately for a period of 7 days. Total RNA was extracted using the RNeasy Mini Kit. RNA purity and quality were evaluated using the Experion RNA StdSens Analysis kit (Bio-rad Laboratories). Gene expression profiling between N/R and I areas was performed using Illumina’s multi-sample format Human HT-12 BeadChip (Illumina Inc.). Differential analysis was performed with the BRB array tools software. Class Comparison test between N/R and I areas was based on paired t-test where N/R and I were paired for each patient. The biological relevance of up- and down-regulated genes was analyses with Ingenuity Pathways Analysis (Ingenuity® Systems). Western blot was performed to confirm certain intermediate expression. Results: From among 47000 probes, 17500 were filtered out. Probes with a p-value below than 0.005 were chosen and classified as up- or down-regulated ones. By this way, 896 differentially expressed genes between N/R and I zones were identified. Among these, 576 genes were upregulated (I/NR > 1.5) and 320 downregulated (I/NR < 0.75). With Ingenuity Pathways Analysis, a significant number of the top ranking differentially expressed genes were identified as inflammatory, Wnt and angiogenic pathways. Interleukin (IL)-6 and -8, chemokines (CXCL1, CXCL2, CXCL5, CXCL6, CXCL16) and arachidonate 5-lipoxygenase (ALOX5) were identified as the most upregulated in I zones in the inflammatory pathway. Interestingly, the alarmin S100A9 was found strongly upregulated in this pathway. Wnt5A and LRP (Low density lipoprotein receptor-related protein) 5 were upregulated whereas FZD (Frizzled homolog) 2 and DKK (dickkopf homolog) 3 were downregulated in the Wnt signaling pathway. Finally, stanniocalcin (STC)-1, an intermediate in angiogenesis was identified as the most upregulated gene in I zones compared to N/R zones. This difference of expression was confirmed at the protein level. Conclusions: Using a unique culture system, this study is the first to identify different expression pattern between two areas of synovial membrane from the same OA patient. These differences concern several key pathways involved in OA pathogenesis, i.e. inflammation, Wnt and angiogenesis. This analysis also provided interesting information regarding new potent intermediates as S100A9 and STC-1. They could be potential targets for chondroitin sulfate, one of the most used molecules in the management of OA. New experiments are being perfomed at the moment to elucidate the potential effect of this molecule on these specific differentially expressed genes in the same culture system. [less ▲]

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See detailL'injection intra-articulaire d'un biomatériau à base de chitosane prévient la progression de l'arthrose expérimentale induite par section du ligament croisé chez le lapin
Oprenyeszk, Frédéric ULg; Chausson, Mickael; Maquet, Véronique et al

in Revue du Rhumatisme (2012), 79(1), 108-109

Introduction La viscosupplémentation par injection intra-articulaire d’acide hyaluronique est recommandée dans le traitement de l’arthrose. Cependant, l’acide hyaluronique a une faible rémanence ... [more ▼]

Introduction La viscosupplémentation par injection intra-articulaire d’acide hyaluronique est recommandée dans le traitement de l’arthrose. Cependant, l’acide hyaluronique a une faible rémanence articulaire, ce qui limite son efficacité dans le temps. Dans ce travail, nous avons testé un nouveau biomatériau formé par le mélange de billes d’alginate-chitosane (AC) associées à un hydrogel visqueux synthétisé au départ de chitosane (H). Ce nouveau biomatériau breveté offre de nombreux avantages :1) biocompatible et non toxique, 2) composé exclusivement au départ de biopolymères d’origine non animale (chitosane et alginate), 3) les billes qui le composent sont élastiques, déformables et exercent un effet anti-inflammatoire et anti-catabolique sur les chondrocytes. Matériels et Méthodes L’arthrose a été induite chez le lapin HYLA albinos par la section du ligament croisé antérieur (LCA). Une semaine après l’intervention chirurgicale, les lapins ont été répartis dans trois groupes expérimentaux et ont bénéficié d’une injection intra-articulaire (900µl) des traitements suivants : billes AC associées à un hydrogel H (Groupe I ; n=7) ; hydrogel H seul (Groupe II ; n = 7) ; liquide physiologique (Groupe III ; n = 7). Des radiographies standards du genou en extension ont été réalisées avant l’intervention et pendant six semaines après l’intervention à raison d’une radiographie par semaine. Après 6 semaines de traitement, les animaux ont été euthanasiés et l’articulation prélevée. Une étude macroscopique du cartilage coloré à l’encre de Chine a été réalisée. Des coupes histologiques colorées à la Safranine-O/fast green provenant des zones portantes dans chaque compartiment ont été évaluées selon le score histologique de l’OARSI (Laverty et al., 2010). Résultats L’analyse des clichés radiologiques montrait une diminution significative (p<0,05) des signes radiologiques d’arthrose après 6 semaines dans le groupe I (billes AC + hydrogel H; 1,57 ± 0,2) en comparaison avec les groupe II (hydrogel H; 2,16 ± 0,47) et III (liquide physiologique ; 3,0 ± 0,43). La macroscopie révélait une tendance à l’amélioration de la taille et du grade des lésions dans le groupe I. La sévérité des lésions histologiques étaient significativement diminuée dans le groupe I (10,98 ± 0,72) par rapport au groupe II (14,43 ± 0,57 ; p<0,01) et au groupe III (14,79 ± 0,62 ; p<0,001). Cet effet était visible au niveau des condyles fémoraux et des plateaux tibiaux. Discussion L’injection intra-articulaire du mélange bille AC + hydrogel H est plus efficace que l’hydrogel H seul, ce qui suggère que les billes AC jouent un rôle dans l’efficacité de ce nouveau traitement. Cette nouvelle formulation pourrait être utilisée pour le traitement par viscosupplémentation de l’arthrose chez l’homme. Conclusion Le nouveau biomatériau formé par le mélange de billes AC et d’un hydrogel visqueux à base de chitosane prévient la progression de l’arthrose chez le lapin. [less ▲]

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See detailFibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis.
Henrotin, Yves ULg; Gharbi, Myriam; Mazzucchelli, Gabriel ULg et al

in Arthritis and Rheumatism (2012), 64(7), 2260-7

OBJECTIVE: This study was undertaken to identify new biomarkers of osteoarthritis (OA) by proteomics analysis and to develop specific immunoassays to detect and quantify them. METHODS: Proteomics analysis ... [more ▼]

OBJECTIVE: This study was undertaken to identify new biomarkers of osteoarthritis (OA) by proteomics analysis and to develop specific immunoassays to detect and quantify them. METHODS: 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. RESULTS: 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. CONCLUSION: Our findings indicate that Fib3-1 and Fib3-2 are potential biochemical markers for the diagnosis of OA. [less ▲]

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See detailLes billes alginate-chitosane : un nouveau biomatériau pour la réparation des lésions du cartilage
Oprenyeszk, Frédéric ULg; Sanchez, Christelle ULg; Dubuc, Jean-Emile et al

in Revue du Rhumatisme (2011), 78(suppl 5), 129-130

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See detailNew alginate-chitosan hydrogel beads with anti-inflammatory and anabolic effects on human chondrocytes
Oprenyeszk, Frédéric ULg; Sanchez, Christelle ULg; Dubuc, Jean-Emile et al

in Arthritis and Rheumatism (2011), 63(10), 697

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See detailCartilage repair in osteoarthritic patients: utopia or real opportunity?
Henrotin, Yves ULg; Dubuc, Jean-Emile

in F1000 Medicine Reports (2009), 1

As medical advances lengthen average life expectancy, osteoarthritis (OA) will become a larger public health problem - not only because it is a manifestation of aging but also because it usually takes ... [more ▼]

As medical advances lengthen average life expectancy, osteoarthritis (OA) will become a larger public health problem - not only because it is a manifestation of aging but also because it usually takes many years to reach clinical relevance. OA is already one of the ten most disabling diseases in industrialized countries. The huge financial burden emphasizes the acute need for new and more effective treatments for articular cartilage defects, especially since there are few disease modifying drugs or treatments for OA. There is no cure for OA and the management of OA is largely palliative, focusing on the alleviation of symptoms. Recent longitudinal non-controlled trials suggest that autologous chondrocyte transplantation techniques, which are indicated for young people with traumatic cartilage defects, could also be used in degenerative defects of elderly people with OA. This report discusses this therapeutic opportunity in view of some recently published data. [less ▲]

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