References of "Osteoarthritis and Cartilage"
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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 occurng 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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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 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 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 detailAltered cartilage phenotype in mice lacking Sirt-1 gene
Gabay, Odile; Zaal, K; Sanchez, Christelle ULg et al

in Osteoarthritis and Cartilage (2013), 21

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See detailDeciphering the role of 75KDA SIRT1 fragment in osteoarthritis
Dvir-Ginzberg, M; Oppenheimer, H; Meir, H et al

in Osteoarthritis and Cartilage (2013), 21

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See detailEquivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study.
Zegels, Brigitte ULg; Crozes, P.; Uebelhart, D. et al

in Osteoarthritis and Cartilage (2013), 21(1), 22-27

OBJECTIVE: Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400 ... [more ▼]

OBJECTIVE: Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA). DESIGN: Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) >/= 7 and pain >/= 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure. RESULTS: After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (<0.001) and VAS (P < 0.01). No significant difference in terms of security and tolerability was observed between the three groups. CONCLUSION: This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient. [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. <br />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. <br />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. <br />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 detailBone sialoprotein: a key mediator of the angiogenic activity of hypertrophic osteoarthritic chondrocytes
Pesesse, Laurence ULg; Sanchez, Christelle ULg; Baudouin, Caroline et al

in Osteoarthritis and Cartilage (2012), 20(S), 122-123

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See detailApplication of biomarkers in the development of drugs intended for the treatment of osteoarthritis.
Kraus, V. B.; Burnett, B.; Coindreau, J. et al

in Osteoarthritis and Cartilage (2011), 19(5), 515-42

OBJECTIVE: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently ... [more ▼]

OBJECTIVE: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. METHODS: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). RESULTS: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. CONCLUSIONS: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. [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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