References of "Osteoarthritis and Cartilage"
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See detailOsteoarthritic sclerotic subchondral osteoblasts secreted elevated concentration of fibulin-3 fragments in vitro
Sanchez, Christelle ULg; Lambert, Cécile ULg; Comblain, Fanny ULg et al

in Osteoarthritis and Cartilage (2016, April), 24(suppl 1), 83

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See detailReview of soluble biomarkers of osteoarthritis: lessons from animal model
Legrand, Catherine ULg; Lambert, Cécile ULg; Comblain, Fanny ULg et al

in Osteoarthritis and Cartilage (2016, April), 24(suppl 1), 88

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See detailBaseline Fibulin3 concentrations are associated with incidence of clinical knee OA after 30 months in overweight and obese women
Runhaar, Jos; Sanchez, Christelle ULg; Henrotin, Yves ULg et al

in Osteoarthritis and Cartilage (2015, April), 23(S2), 83

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See detailANALGESIC EFFICACY AND SAFETY OF CURCUMINOIDS IN CLINICAL PRACTICE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Henrotin, Yves ULg; Sahebkar, A

in Osteoarthritis and Cartilage (2015), 23(S2), 356

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See detailDiabetes is a risk factor for knee osteoarthritis progression
Eymard, F; Parsons, C; Edwards, M et al

in Osteoarthritis and Cartilage (2015), 23

Purpose Recent studies have suggested that metabolic factors (obesity, diabetes, hypertension and dyslipidemia) and their clustering in metabolic syndrome (MetS) might be involved in the pathophysiology ... [more ▼]

Purpose Recent studies have suggested that metabolic factors (obesity, diabetes, hypertension and dyslipidemia) and their clustering in metabolic syndrome (MetS) might be involved in the pathophysiology of knee osteoarthritis (OA). We investigated their impact on radiographic progression by an annualised measure of the joint space narrowing (JSN) of the medial tibiofemoral compartment. Methods 559 patients older than 50 years with symptomatic knee OA were recruited for the placebo arm of the SEKOIA trial. The presence of diabetes, hypertension and dyslipidemia was determined at baseline interview. BMI was calculated, obesity was considered >30 kg/m2. MetS was defined by the sum of metabolic factors ≥3. Minimal medial tibiofemoral joint space on plain radiographs was measured by an automated method at baseline and then annually for up to 3 years. Results The mean age of patients was 62.8 [62.2-63.4] years; 392 were women. A total of 43.8% was obese, 6.6% had type 2 diabetes, 45.1% hypertension, 27.6% dyslipidemia and 13.6% MetS. Mean annualised JSN was greater for patients with type 2 diabetes than without diabetes (0.26 [-0.35 - -0.17] vs. 0.14 [-0.16 - -0.12] mm; p=0.001). This association remained significant after adjustment for sex, age, BMI, hypertension and dyslipidemia (p=0.018). In subgroup analysis, type 2 diabetes was a significant predictor of JSN in males but not females. The other metabolic factors and MetS were not associated with annualised JSN. Conclusion Type 2 diabetes was a predictor of joint space reduction in men with established knee OA. No relationships were found between MetS or other metabolic factors and radiographic progression. [less ▲]

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See detailRecommendations for an update of the 2010 European regulatory guideline on clinical investigation of medical products used in the treatment of osteoarthritis and reflections about related clinically relevant outcomes: expert consensus statement.
Reginster, Jean-Yves ULg; REITER-NIESERT, S.; Bruyère, Olivier ULg et al

in Osteoarthritis and Cartilage (2015), 23

Objective: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on ... [more ▼]

Objective: The European Society on Clinical and Economic aspects of Osteoporosis and Osteoarthritis (ESCEO) organised a working group to evaluate the need for updating the current European guideline on clinical investigation of drugs used in the treatment of osteoarthritis (OA). Design: Areas of potential attention were identified and the need for modifications, update or clarification was examined. Proposals were then developed based on literature reviews and through a consensus process. Results: It was agreed that the current guideline overall still reflects the current knowledge in OA, although two possible modifications were identified. The first relates to the number and timing of measurements required as primary endpoints during clinical trials of symptom-relieving drugs, either drugs with rapid onset of action or slow acting drugs. The suggested modifications are intended to take into consideration the time related clinical need and expected time response to these drugs e i.e., a more early effect for the first category in addition to the maintenance of effect, a more continuous benefit over the long-term for the latter e in the timing of assessments. Secondly, values above which a benefit over placebo should be considered clinically relevant were considered. Based on literature reviews, the most consensual values were determined for primary endpoints of both symptom-relieving drugs (i.e., pain intensity on a visual analogue scale (VAS)) and disease-modifying drugs (i.e., radiographic joint-space narrowing). [less ▲]

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See detailRestriction of spontaneous and prednisolone-induced leptin production to dedifferentiated state in human hip OA chondrocytes: role of Smad1 and b-catenin activation
CHARLIER, Edith ULg; MALAISE, Olivier ULg; Zeddou, Mustapha et al

in Osteoarthritis and Cartilage (2015)

Objective: The aetiology of OA is not fully understood although several adipokines such as leptin are known mediators of disease progression. Since leptin levels were increased in synovial fluid compared ... [more ▼]

Objective: The aetiology of OA is not fully understood although several adipokines such as leptin are known mediators of disease progression. Since leptin levels were increased in synovial fluid compared to serum in OA patients, it was suggested that joint cells themselves could produce leptin. However, exact mechanisms underlying leptin production by chondrocytes are poorly understood. Nevertheless, prednisolone, although displaying powerful anti-inflammatory properties has been recently reported to be potent stimulator of leptin and its receptor in OA synovial fibroblasts. Therefore, we investigated, in vitro, spontaneous and prednisolone-induced leptin production in OA chondrocytes, focusing on transforming growth factor-b (TGFb) and Wnt/b-catenin pathways. Design: We used an in vitro dedifferentiation model, comparing human freshly isolated hip OA chondrocytes cultivated in monolayer during 1 day (type II, COL2A1 þ; type X, COL10A1 þ and type I collagen, COL1A1 ") or 14 days (COL2A1 "; COL10A1 " and COL1A1þ). Results: Leptin expression was not detected in day1 OA chondrocytes whereas day14 OA chondrocytes produced leptin, significantly increased with prednisolone. Activin receptor-like kinase 1 (ALK1)/ALK5 ratio was shifted during dedifferentiation, from high ALK5 and phospho (p)-Smad2 expression at day1 to high ALK1, endoglin and p-Smad1/5 expression at day14. Moreover, inactive glycogen synthase kinase 3 (GSK3) and active b-catenin were only found in dedifferentiated OA chondrocytes. Smad1 and b-catenin but not endoglin stable lentiviral silencing led to a significant decrease in leptin production by dedifferentiated OA chondrocytes. Conclusions: Only dedifferentiated OA chondrocytes produced leptin. Prednisolone markedly enhanced leptin production, which involved Smad1 and b-catenin activation [less ▲]

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See detailBone sialoprotein as a potential key factor implicated in the pathophysiology of osteoarthritis
Pesesse, Laurence ULg; Sanchez, Christelle ULg; Walsh, David et al

in Osteoarthritis and Cartilage (2014), 22(4), 547-56

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See detailOARSI guidelines for the non-surgical management of knee osteoarthritis
McAlindon; Henrotin, Yves ULg

in Osteoarthritis and Cartilage (2014), 22(3), 363-388

This paper presents concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis, intended to inform patients, physicians and allied ... [more ▼]

This paper presents concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis, intended to inform patients, physicians and allied healthcare professionnal worlwide. [less ▲]

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See detailImpact of components of the metabolic syndrome on knee osteoarthritis progression in the SEKOIA study
Eymard, F; Edwards, M; Parsons, C et al

in Osteoarthritis and Cartilage (2014), 22(1), 376

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See detailStrontium ranelate decreases the number of rapid radiological progressors from the first year in SEKOIA study
Chevalier, X; Richette, P; Bruyère, Olivier ULg et al

in Osteoarthritis and Cartilage (2014), 22(1), 461

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See detailOARSI recommended performance-based tests to assess clinical function in osteoathritis of hip and knee: author's reply
Dobson, Flora; Henrotin, Yves ULg

in Osteoarthritis and Cartilage (2013), 21(10), 1625-1626

The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements ... [more ▼]

The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements. These tests are complementary to patient-reported measures and are recommended as prospective outcome measures in future OA research and to assist decision-making in clinical practice. Further research should be directed to expanding the measurement-property evidence of the recommended tests. [less ▲]

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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 detailPrevalence of naturally occuring cartilage defects in the ovine knee
Vandeweerd, Jean-Michel; Hontoir, Fanny; Kirschvink, Nathalie et al

in Osteoarthritis and cartilage (2013), 21

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See detailOARSI recommended performance-based tests to assess physical function in people with established hip and knee osteoarthritis
Dobson, F.; Hinman, R.S.; Roos, E.M. et al

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

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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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