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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 detailInvestigation of potential new targets for the diagnosis and/or the treatment of osteoarthritis
Lambert, Cécile ULg; Dubuc, J.-E.; Montell, E. et al

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

Purpose: Synovial inflammation plays a key role in the pathophysiology process of osteoarthritis (OA). We have previously compared the gene expression pattern of synovial cells isolated from inflammatory ... [more ▼]

Purpose: Synovial inflammation plays a key role in the pathophysiology process of osteoarthritis (OA). We have previously compared the gene expression pattern of synovial cells isolated from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same OA patient. We identified a large number of mediators belonging to key pathways involved in OA pathogenesis. The aim of this study was to validate different potential new targets for the diagnosis and/or the treatment OA. Methods: Synovial cells (SC) were isolated from synovial specimens obtained from OA patients undergoing knee replacement. The inflammatory status of the synovial membrane was characterized according to macroscopic criteria. The biopsies from N/R and I areas were cultured separately for a period of 7 days. Microarray gene expression profiling between N/R and I areas was performed. The biological relevance of up- and down-regulated genes was analyzed with Ingenuity Pathways Analysis. Western blot and immunohistochemistry confirmed the identified genes most differentially expressed in the key pathways. The production of the triggering receptor expressed on myeloid cells-1 (TREM1), the alarmin S100 calcium binding protein A9 (S100A9), the wingless-type MMTV integration site family, member 5A (Wnt-5A) and the stanniocalcin 1 (STC1) were evaluated by Western blot. S100A9, hyaluronan synthase-1 (HAS1) and STC1 expression and localization were investigated by immunohistochemistry. Results: 896 genes differentially expressed in N/R and I areas were identified. The key pathways were related to inflammation, cartilage metabolism, Wnt signaling and angiogenesis. In the inflammatory gene pattern, TREM1 and S100A9 were strongly upregulated. We validated the production of these proteins in OA synovial biopsies by Western blot. TREM1 and S100A9 were increased in I compared to N/R synovial cells culture. S100A9 was observed in the perivascular area and in sublining cells in I synovial biopsies, but not in N/R biopsies. An increased staining was also observed in the intima lining layer of I when compared to N/R biopsies. The most upregulated anabolism enzyme in I synovial biopsies was HAS1. Using immunohistochemistry, we observed in I areas an increase of the HAS1-positive cells mainly in the intima lining. We also studied the protein production of Wnt-5A, the most upregulated intermediate of Wnt signaling pathway. The protein level was increased in I compared to N/R areas. Finally, in the angiogenesis pathway, one the most u-regulated gene was STC1. A significant increase of STC1 production was observed in I areas compared to N/R areas by Western blot. This result was also supported by the immunohistochemical analysis. In I area, the staining for STC1 was more intense in perivascular and sublining cells. Conclusions: Synovial membrane inflammation is a key target for OA treatments. In this work, we have identified proteins involved in the synovitis pathways like angiogenesis, cells infiltration and matrix remodeling. These proteins could be targeted by drugs and used as companion biomarkers for evaluating their efficacy. Although qualitative, our results could also yield to the identification of markers of the disease. This investigation has to be further pursued. [less ▲]

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See detailEffects of chondroitin sulfate on the gene expression profile in the inflamed synovial membrane
Lambert, Cécile ULg; Dubuc, J-E; Montell, E. et al

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

Purpose: The aim of the present work was to identify the differentially expressed genes between the inflammatory (I) and normal/reactive (N/R) synovial areas using a unique ex vivo culture model. In a ... [more ▼]

Purpose: The aim of the present work was to identify the differentially expressed genes between the inflammatory (I) and normal/reactive (N/R) synovial areas using a unique ex vivo culture model. In a second step, we investigated the genetic modulatory effects of chondroitin sulfate (CS) in this model. 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 according to macroscopic criteria. 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 in the absence or in the presence of highly purified bovine CS (200 µg/ml, Bioibérica S.A., Barcelona, Spain). 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 N/R and I conditions, N/R and N/R-CS conditions and I and I-CS conditions was based on paired t-test where N/R and I, N/R and N/R-CS and I and I-CS were paired for each patient. The biological relevance of up- and down-regulated genes was analyses with Ingenuity Pathways Analysis (Ingenuity® Systems). Results: From among 47000 probes, 18253 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, 465 differentially expressed genes between N/R and I areas were identified. Many inflammatory mediators appear differentially expressed. The interferon alpha-inductible protein 6 (IFI6) was the most up-regulated. We also identified the hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1), the cathepsin K (CTSK), the chemokine (C-X-C motif) ligand 1 (CXCL1) and the EBV-induced G-protein coupled receptor 2 (EBI2). The differential expression of intermediates involved in angiogenesis pathway was also revealed between N/R and I areas. Among them, R-spondin-3 (RSPO3), the secreted phopshoprotein 1 (SPP1) and aquaporin 9 (AQP9) were up-regulated whereas ADAMTS1 was down-regulated. Finally, in the Wnt signaling, RSPO3 was up-regulated unlike dickkopf homolog 3 (DKK3) which was in turn down-regulated. We next performed a class comparison test between N/R and N/R-CS in one hand and between I and I-CS the other hand. 489 genes were identified as differentially expressed genes between N/R and N/R-CS conditions while 219 genes were identified between I and I-CS conditions. In this latter, our attention was focused on the down-regulated genes. Among them, we identified a number implicated in angiogenesis and cell migration pathways. Thus, the endothelial cell-specific molecule-1 (ESM1), the Transmembrane-4-L-six-family-1 (TM4SF1), the 5’-Ectonucleotidase (NT5E) and the growth arrest-specific gene 6 (GAS6) were down-regulated by CS. Conclusions: Our work demonstrates the differential gene expression profile between paired non inflammatory and normal/reactive areas of synovial membrane as well as the modulatory effects of CS on gene expression in the inflammatory areas, especially regarding genes involved in both angiogenesis and cell migration. [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 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 detailCharacterization of synovial angiogenesis in osteoarthritis patients and its modulation by chondroitin sulfate
Lambert, Cécile ULg; Mathy-Hartert, Marianne; Dubuc, JE et al

in Arthritis Research & Therapy (2012), 14(2), 58

INTRODUCTION: This work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane ... [more ▼]

INTRODUCTION: This work aimed at comparing the production of inflammatory and pro- and anti-angiogenic factors by normal/reactive (N/R) or inflammatory (I) areas of the osteoarthritic synovial membrane. The effects of interleukin (IL)-1β and chondroitin sulfate (CS) on the expression of pro- and anti-angiogenic factors by synovial fibroblasts cells (SFC) were also studied. METHODS: Biopsies from N/R or from I areas of osteoarthritic synovial membrane were collected at the time of surgery. 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. We assessed the expression of CD45, von Willebrand factor and vascular endothelial growth factor (VEGF) antigen by immunohistochemistry in both N/R and I biopsies. The production of IL-6, -8, VEGF and thrombospondin (TSP)-1 by N/R or I synovial cells was quantified by ELISA. SFC were cultured in the absence or in the presence of IL-1β (1 ng/ml) and with or without CS (10, 50, 200 μg/ml). Gene expression of pro-angiogenic factors (VEGF, basic fibroblast growth factor (bFGF), nerve growth factor (NGF), matrix metalloproteinase (MMP)-2 and angiopoietin (ang)-1) and anti-angiogenic factors (vascular endothelial growth inhibitor (VEGI), TSP-1 and -2) were determined by real time RT-PCR. Production of VEGI and TSP-1 was also estimated by ELISA. RESULTS: Immunohistochemistry showed the increase of lymphocyte infiltration, vascular density and VEGF expression in I compared to 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. The expression of pro-angiogenic factors by SFC was stimulated by IL-1β. A time dependent regulation of the expression of anti-angiogenic factor genes was observed. IL-1β stimulated the expression of anti-angiogenic factor genes but inhibited it after 24 h. CS reversed the inhibitory effect of IL-1β on anti-angiogenic factors, VEGI and TSP-1. CONCLUSIONS: We demonstrated that synovial biopsies from I areas expressed a pro-angiogenic phenotype. IL-1β induced an imbalance between pro- and anti-angiogenic factors in SFC and CS tended to normalize this IL-1β-induced imbalance, providing a new possible mechanism of action of this drug. [less ▲]

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See detailNutraceuticals: do they represent a new era in the management of osteoarthritis? - a narrative review from the lessons taken with five products.
Henrotin, Yves ULg; Lambert, Cécile ULg; Couchourel, D. et al

in Osteoarthritis and Cartilage (2011), 19(1), 1-21

OBJECTIVES: The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health ... [more ▼]

OBJECTIVES: The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health, physiological or functional benefit on osteoarthritis (OA) were gathered and the level of evidence relative to each of these ingredients was highlighted. METHODOLOGY: Relevant scientific data (positive or not) regarding OA were searched for five groups of compounds (avocado/soybean unsaponifiables (ASU), n-3 polyunsaturated fatty acids, collagen hydrosylates (CHs), vitamin D, polyphenols) within preclinical (in vitro and in vivo), epidemiological, and clinical studies. The following criteria were evaluated to assess the methodology quality of each study: (1) study question; (2) study population; (3) primary endpoint; (4) study design (randomization, control, blinding, duration of follow up); (5) data analysis and interpretation. A scientific consensus was determined for all studied nutraceuticals to evaluate their efficacy in OA. RESULTS: The studied compounds demonstrated different potencies in preclinical studies. Most of them have demonstrated anti-catabolic and anti-inflammatory effects by various inhibitory activities on different mediators. Vitamin D showed a pro-catabolic effect in vitro and the polyphenol, Genistein, had only anti-inflammatory potency. The evaluation of the clinical data showed that ASU was the only one of the studied ingredients to present a good evidence of efficacy, but the efficient formulation was considered as a drug in some countries. Pycnogenol showed moderate evidence of efficacy, and vitamin D and collagen hydrolysate demonstrated a suggestive evidence of efficacy, whereas curcumin, epigallocatechin-3-gallate (EGCG) and resveratrol had only preclinical evidence of efficacy due to the lack of clinical data. The literature gathered for n-3 PUFA, nobiletin and genistein was insufficient to conclude for their efficacy in OA. CONCLUSION: Additional data are needed for most of the studied nutraceuticals. Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alternates for OA management. Their use should be driven by any recommendations. [less ▲]

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See detailSynovium angiogenesis in osteoarthritis: a new therapy target for chondroitin sulfate
Mathy, Marianne ULg; Lambert, Cécile ULg; Dubuc, Jean Emile et al

in Osteoarthritis and Cartilage (2010, October), 18

Purpose: Osteoarthritis (OA) is an important cause of pain and disability in the ageing population. Angiogenesis and inflammation are closely integrated process in OA and may contribute to its ... [more ▼]

Purpose: Osteoarthritis (OA) is an important cause of pain and disability in the ageing population. Angiogenesis and inflammation are closely integrated process in OA and may contribute to its pathogenesis, as well as, affect disease progression and pain. Chondroitin sulfate (CS) is a symptomatic slow acting drug for OA and there is strong evidence suggesting that CS may also be a structure disease modifying osteoarthritis drug. The mechanisms underlying these effects remain poorly understood. This work aimed to demonstrate the relation between inflammation and angiogenesis of synovium and to study the effect of CS on synovium angiogenesis. [less ▲]

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See detailSynovium angiogenesis in osteoarthritis: a new therapy target for chondroitin sulfate
Mathy, Marianne ULg; Lambert, Cécile ULg; Dubuc, Jean Emile et al

Poster (2010, September)

Osteoarthritis (OA) is an important cause of pain and disability in the ageing population. Angiogenesis and inflammation are closely integrated process in OA and may contribute to its pathogenesis, as ... [more ▼]

Osteoarthritis (OA) is an important cause of pain and disability in the ageing population. Angiogenesis and inflammation are closely integrated process in OA and may contribute to its pathogenesis, as well as, affect disease progression and pain. Chondroitin sulfate (CS) is a symptomatic slow acting drug for OA and there is strong evidence suggesting that CS may also be a structure disease modifying osteoarthritis drug. The mechanisms underlying these effects remain poorly understood. This work aimed to demonstrate the relation between inflammation and angiogenesis of synovium and to study the effect of CS on synovium angiogenesis. [less ▲]

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See detailLa chondroitine sulfate stimule la production des facteurs anti angiogéniques TSP-1 et VEGI par les synoviocytes arthrosiques : un nouveau mécanisme d’action pour cette molécule.
Mathy, Marianne ULg; Lambert, Cécile ULg; Dubuc, Jean Emile et al

Poster (2010, September)

: La chondroïtine sulfate (CS), la glucosamine sulfate (GS), la glucosamine HCl (GH) et l’acide hyaluronique (AH) sont des anti-arthrosiques symptomatiques d’action lente (AASAL) dont l’utilisation est ... [more ▼]

: La chondroïtine sulfate (CS), la glucosamine sulfate (GS), la glucosamine HCl (GH) et l’acide hyaluronique (AH) sont des anti-arthrosiques symptomatiques d’action lente (AASAL) dont l’utilisation est recommandée dans le traitement de l’arthrose. Les mécanismes d’action de ces molécules demeurent mal compris. Notre étude a comme objectif d’étudier les effets de ces molécules sur la production de médiateurs impliqués dans l’angiogenèse de la membrane synoviale (MS) arthrosique. [less ▲]

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See detailChondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to clinical recommendations
Henrotin, Yves ULg; Mathy, Marianne ULg; Sanchez, Christelle ULg et al

in Therapeutic Advances in Musculoskeletal Disease (2010), 2(6), 335-348

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