References of "Malaise, Michel"
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See detailDid Osteoblastic Cell Therapy Improve the Prognosis of Prefracture Osteonecrosis of the Femoral Head? A Randomized, Controlled Trial
HAUZEUR, Jean-Philippe ULiege; LECHANTEUR, Chantal ULiege; BAUDOUX, Etienne ULiege et al

in Clinical Orthopaedics and Related Research (in press)

Background In patients with nontraumatic osteonecrosis of the femoral head (ONFH), implantation of bone marrow aspirate concentrate (BMAC) could delay the progression of osteonecrosis and improve symptoms ... [more ▼]

Background In patients with nontraumatic osteonecrosis of the femoral head (ONFH), implantation of bone marrow aspirate concentrate (BMAC) could delay the progression of osteonecrosis and improve symptoms in pre-fractureONFH. However, the BMAC content, especially in osteoblastic stem cells, could have an important individual variability. [less ▲]

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See detailMacrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p
GUIOT, Julien ULiege; Cambier, Maureen ULiege; Boeckx, Amandine ULiege et al

in Thorax (2020)

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs ... [more ▼]

Introduction: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology and cure. Recent studies have reported a dysregulation of exosomal microRNAs (miRs) in the IPF context. However, the impact of IPF-related exosomal miRs on the progression of pulmonary fibrosis is unknown. Methods: Two independent cohorts were enrolled at the ambulatory care polyclinic of Liège University. Exosomes from sputum were obtained from 19 patients with IPF and 23 healthy subjects (HSs) (cohort 1), and the ones from plasma derived from 14 patients with IPF and 14 HSs (cohort 2). Exosomal miR expression was performed by quantitative reverse transcription–PCR. The functional role of exosomal miRs was assessed in vitro by transfecting miR mimics in human alveolar epithelial cells and lung fibroblasts. Results: Exosomal miR analysis showed that miR-142-3p was significantly upregulated in sputum and plasma of patients with IPF (8.06-fold, p<0.0001; 1.64 fold, p=0.008, respectively). Correlation analysis revealed a positive association between exosomal miR-142-3p and the percentage of macrophages from sputum of patients with IPF (r=0.576, p=0.012), suggesting macrophage origin of exosomal miR-142-3p upregulation. The overexpression of miR-142-3p in alveolar epithelial cells and lung fibroblasts was able to reduce the expression of transforming growth factor β receptor 1 (TGFβ-R1) and profibrotic genes. Furthermore, exosomes isolated from macrophages present antifibrotic properties due in part to the repression of TGFβ-R1 by miR-142-3p transfer in target cells. Discussion: Our results suggest that macrophage-derived exosomes may fight against pulmonary fibrosis progression via the delivery of antifibrotic miR-142–3 p to alveolar epithelial cells and lung fibroblasts. [less ▲]

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See detailExosomal Long Non-Coding RNAs in Lung Diseases
Poulet, Christophe ULiege; NJOCK, Makon-Sébastien ULiege; MOERMANS, Catherine ULiege et al

in International Journal of Molecular Sciences (2020), 21(10), 3580

Within the non-coding genome landscape, long non-coding RNAs (lncRNAs) and their secretion within exosomes are a window that could further explain the regulation, the sustaining, and the spread of lung ... [more ▼]

Within the non-coding genome landscape, long non-coding RNAs (lncRNAs) and their secretion within exosomes are a window that could further explain the regulation, the sustaining, and the spread of lung diseases. We present here a compilation of the current knowledge on lncRNAs commonly found in Chronic Obstructive Pulmonary Disease (COPD), asthma, Idiopathic Pulmonary Fibrosis (IPF), or lung cancers. We built interaction networks describing the mechanisms of action for COPD, asthma, and IPF, as well as private networks for H19, MALAT1, MEG3, FENDRR, CDKN2B-AS1, TUG1, HOTAIR, and GAS5 lncRNAs in lung cancers. We identified five signaling pathways targeted by these eight lncRNAs over the lung diseases mentioned above. These lncRNAs were involved in ten treatment resistances in lung cancers, with HOTAIR being itself described in seven resistances. Besides, five of them were previously described as promising biomarkers for the diagnosis and prognosis of asthma, COPD, and lung cancers. Additionally, we describe the exosomal-based studies on H19, MALAT1, HOTAIR, GAS5, UCA1, lnc-MMP2-2, GAPLINC, TBILA, AGAP2-AS1, and SOX2-OT. This review concludes on the need for additional studies describing the lncRNA mechanisms of action and confirming their potential as biomarkers, as well as their involvement in resistance to treatment, especially in non-cancerous lung diseases. [less ▲]

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See detailAsthma and COPD Are Not Risk Factors for ICU Stay and Death in Case of SARS-CoV2 Infection
CALMES, Doriane ULiege; Graff, Sophie ULiege; MAES, Nathalie ULiege et al

in Journal of Allergy and Clinical Immunology: In Practice (2020)

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See detailGlycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis
Ciregia, Federica ULiege; Baiwir, Dominique ULiege; COBRAIVILLE, Gaël ULiege et al

in Journal of Translational Medicine (2020), 18(1),

Background: Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein ... [more ▼]

Background: Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. Methods: In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC-MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). Results: We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. Conclusions: This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment. © 2020 The Author(s). [less ▲]

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See detailTargeted proteomics reveals serum amyloid A variants and alarmins S100A8-S100A9 as key plasma biomarkers of rheumatoid arthritis
Nys, Gwenaël ULiege; COBRAIVILLE, Gaël ULiege; Servais, Anne-Catherine ULiege et al

in Talanta (2019)

Serum amyloid A (SAA) and S100 (S100A8, S100A9 and S100A12) proteins were previously identified as biomarkers of interest for rheumatoid arthritis (RA). Among SAA family, two closely related isoforms (SAA ... [more ▼]

Serum amyloid A (SAA) and S100 (S100A8, S100A9 and S100A12) proteins were previously identified as biomarkers of interest for rheumatoid arthritis (RA). Among SAA family, two closely related isoforms (SAA-1 and SAA-2) are linked to the acute-phase of inflammation. They respectively exist under the form of three (α, β, and γ) and two (α and β) allelic variants. We developed a single run quantitative method for these protein variants and investigated their clinical relevance in the context of RA. The method was developed and validated according to regulations before being applied on plasma coming from RA patients (n = 46), other related inflammatory pathologies (n = 116) and controls (n = 62). Depending on the activity score of RA, SAA1 isoforms (mainly of SAA1α and SAA1β subtypes) were found to be differentially present in plasma revealing their dual role during the development of RA. In addition, the weight of SAA1α in the total SAA response varied from 32 to 80% depending on the pathology studied. A negative correlation between SAA1α and SAA1β was also highlighted for RA early-onset (r = −0.41). SAA2 and S100A8/S100A9 proteins were significantly overexpressed compared to control samples regardless of RA stage. The pathophysiological relevance of these quantitative and qualitative characteristics of the SAA response remains unknown. However, the significant negative correlation observed between SAA1α and SAA1β levels in RA early-onset suggests the existence of still unknown regulatory mechanisms in these diseases. [less ▲]

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See detail15-Deoxy-Δ-12, 14-prostaglandin J2 acts cooperatively with prednisolone to reduce TGF-β-induced pro-fibrotic pathways in human osteoarthritis fibroblasts
Vaamonde-Garcia, Carlos; MALAISE, Olivier ULiege; CHARLIER, Edith ULiege et al

in Biochemical Pharmacology (2019)

BACKGROUND/AIMS: Synovial fibrosis is a pathological process that is observed in several musculoskeletal disorders and characterized by the excessive deposition of extracellular matrix, as well as cell ... [more ▼]

BACKGROUND/AIMS: Synovial fibrosis is a pathological process that is observed in several musculoskeletal disorders and characterized by the excessive deposition of extracellular matrix, as well as cell migration and proliferation. Despite the fact that glucocorticoids are widely employed in the treatment of rheumatic pathologies such as osteoarthritis (OA) and rheumatoid arthritis, the mechanisms by which glucocorticoids act in the joint and their impacts on pro-fibrotic pathways are still unclear. MATERIALS: Human OA synovial fibroblasts were obtained from knee and hip joints. Cells were treated with prednisolone (1 mM) or transforming growth factor-beta 1 (TGF-β1) (10 ng/ml) for 1 and 7 days for quantification of RNA and protein expression (by real-time quantitative reverse transcription-PCR and western blot, respectively), 72 h for immunocytochemistry analysis, and 48 h for proliferation (by BrdU assay) and migration (by wound assay) studies. In addition, cells were preincubated with prednisolone and/or the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) for 6 h before adding TGF-β1. pSmad1/5, pSmad2 and β-catenin levels were analyzed by Western blot. The activin receptor-like kinase-5 (ALK-5) inhibitor (SB-431542) was employed for the mechanistic assays. RESULTS: Prednisolone showed a predominant anti-fibrotic impact on fibroblast-like synoviocytes as it attenuated the spontaneous and TGF-β-induced gene expression of pro-fibrotic markers. Prednisolone also reduced α-sma protein and type III collagen levels, as well as cell proliferation and migration after TGF-β stimulation. However, prednisolone did not downregulate the gene expression of all the pro-fibrotic markers tested and did not restore the reduced PPAR-γ levels after TGF-β stimulation. Interestingly, anti-fibrotic actions of the glucocorticoid were reinforced in the presence of the PPAR-γ agonist 15d-PGJ2. Combined pretreatment modulated Smad2/3 levels and, similar to the ALK-5 inhibitor, blocked β-catenin accumulation elicited by TGF-β. CONCLUSIONS: Prednisolone, along with 15d-PGJ2, modulates pro-fibrotic pathways activated by TGF-β in synovial fibroblasts at least partially through the inhibition of ALK5/Smad2 signaling and subsequent β-catenin accumulation. These findings shed light on the potential therapeutic effects of glucocorticoids treatment combined with a PPAR-γ agonist against synovial fibrosis, although future studies are warranted to further evaluate this concern. [less ▲]

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See detailCEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
DEROYER, Céline ULiege; CHARLIER, Edith ULiege; NEUVILLE, Sophie ULiege et al

in Cell Death and Disease (2019)

CEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and ... [more ▼]

CEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, αSMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated β-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted αSMA expression, a fibrosis marker, and TGFβ signaling towards the p-Smad2/3 (Alk5/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1/5 (Alk1) pathway. αSMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with αSMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into “chondro-myo-fibroblasts” expressing α-SMA and type III collagen, two fibrosis markers. Moreover, these “chondro-myo-fibroblasts” were found in OA cartilage but not in healthy cartilage. [less ▲]

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See detailBio-optimized Curcuma longa extract is efficient on knee osteoarthritis pain: A double-blind multicenter randomized placebo controlled three-arm study
Henrotin, Yves ULiege; Malaise, Michel ULiege; Wittoek, Ruth et al

in Arthritis Research and Therapy (2019), 21(1),

Objectives: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). Methods: A prospective, randomized, 3-month, double-blind ... [more ▼]

Objectives: Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA). Methods: A prospective, randomized, 3-month, double-blind, multicenter, three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints. Results: One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012). Conclusions: BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016 - retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5 - Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621). © 2019 The Author(s). [less ▲]

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See detailHyaluronan derivative HYMOVIS® increases cartilage volume and type ii collagen turnover in osteoarhritic knee: Data from MOKHA study
Henrotin, Yves ULiege; Bannuru, R.; Malaise, Michel ULiege et al

in BMC Musculoskeletal Disorders (2019), 20(1),

Background: The objective of this pilot study was to identify biological, clinical or structural biomarkers of an intra-articular hyaluronic acid injection efficacy (HYMOVIS®) for the design of a larger ... [more ▼]

Background: The objective of this pilot study was to identify biological, clinical or structural biomarkers of an intra-articular hyaluronic acid injection efficacy (HYMOVIS®) for the design of a larger placebo-controlled clinical trial studying the disease-modifying activity of this treatment. Methods: Forty six patients with symptomatic knee Osteoarthritis (OA) were enrolled in this open-label, prospective, multicenter, pilot study. Patients received two treatment cycles of intra-articular injections (3 mL) of HYMOVIS® (8 mg/mL of hyaluronic acid hexadecylamide) at 6 months interval. Each treatment cycle involved two intra-articular injections 1 week apart. All patients had Magnetic Resonance Imaging (MRI) of the target knee at baseline and 1 year, and blood samples to assess joint biomarkers. The primary outcome was the change in type II collagen-specific biomarkers (Coll2-1, Coll2-1NO2 and CTX-II) after HYMOVIS® treatment versus baseline. Secondary endpoints included levels changes in aggrecan chondroitin sulfate 846 epitope (CS-846), Cartilage Oligomeric Matrix Protein (COMP), procollagen type II N-terminal propeptide (PIIANP), Matrix Metalloprotease (MMP)-3, Myeloperoxidase (MPO) and Interleukin (IL)-6 serum biomarkers, the ratio Coll2-1/PIIANP, CTX-II/PIIANP, variation of MRI cartilage volume, and Knee injury and Osteoarthritis Outcome Score (KOOS) index. Results: Coll2-1 serum levels significantly increased overtime while Coll2-1NO2 levels were only increased at D360. Serum PIIANP levels also progressively and significantly enhanced with time. In contrast, other serum biomarker levels including CTX-II, CS-846, COMP, MMP-3, MPO or IL-6 did not change significantly overtime. Interestingly, the ratios Coll2-1/PIIANP and CTX-II/PIIANP decreased, indicating a decrease of cartilage catabolism. Compared to baseline value, MRI cartilage volume and thickness increased in lateral femoral and lateral trochlea compartments and not in medial compartment. These results, in addition to an improvement of T2 mapping score suggest a positive structural effect of the product. Interestingly, WORMS effusion score, an indicator of synovitis, significantly decreased. Finally, global KOOS score and subscales significantly increased overtime while pain at rest, walking pain and patients or investigators global assessment of disease activity decreased. The safety profile was favorable with a low incidence of injection-site pain. Conclusion: HYMOVIS®, a well-tolerated intra-articular treatment, significantly enhanced type II collagen turnover as suggested by the increase in Coll2-1 and PIIANP levels and cartilage volume observed by MRI in lateral knee compartment. Importantly, this study provides critical information for the design of a larger phase III clinical trial investigating Disease Modifying effect of HYMOVIS®. Trial registration: http://www.isrctn.com/ISRCTN12227846 11/02/2015. © 2019 The Author(s). [less ▲]

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See detailExosomal miRNAs in Lung Diseases: From Biologic Function to Therapeutic Targets.
GUIOT, Julien ULiege; Struman, Ingrid ULiege; Louis, Edouard ULiege et al

in Journal of clinical medicine (2019), 8(9),

Increasing evidence suggests the potential role of extracellular vesicles (EVs) in many lung diseases. According to their subcellular origin, secretion mechanism, and size, EVs are currently classified ... [more ▼]

Increasing evidence suggests the potential role of extracellular vesicles (EVs) in many lung diseases. According to their subcellular origin, secretion mechanism, and size, EVs are currently classified into three subpopulations: exosomes, microvesicles, and apoptotic bodies. Exosomes are released in most biofluids, including airway fluids, and play a key role in intercellular communication via the delivery of their cargo (e.g., microRNAs (miRNAs)) to target cell. In a physiological context, lung exosomes present protective effects against stress signals which allow them to participate in the maintenance of lung homeostasis. The presence of air pollution alters the composition of lung exosomes (dysregulation of exosomal miRNAs) and their homeostatic property. Indeed, besides their potential as diagnostic biomarkers for lung diseases, lung exosomes are functional units capable of dysregulating numerous pathophysiological processes (including inflammation or fibrosis), resulting in the promotion of lung disease progression. Here, we review recent studies on the known and potential role of lung exosomes/exosomal miRNAs, in the maintaining of lung homeostasis on one hand, and in promoting lung disease progression on the other. We will also discuss using exosomes as prognostic/diagnostic biomarkers as well as therapeutic tools for lung diseases. [less ▲]

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See detailBiomarkers in systemic sclerosis-associated interstitial lung disease: review of the literature.
BONHOMME, Olivier ULiege; ANDRE, Béatrice ULiege; GESTER, Fanny ULiege et al

in Rheumatology (Oxford, England) (2019)

SSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc ... [more ▼]

SSc is a rare disease of unknown origin associated with multiple organ involvement. One of the major complications that drives the mortality of SSc patients is interstitial lung disease. The course of SSc-interstitial lung disease progression has a wide spectrum. Since the treatment is based on aggressive immunosuppression it should not be given to stable or non-progressing disease. The correct identification of disease with high risk of progression remains a challenge for early therapeutic intervention, and biomarkers remain urgently needed. In fact, eight categories of biomarkers have been identified and classified according to the different biological pathways involved. The purpose of this article is to describe the main biomarkers thought to be of interest with clinical value in the diagnosis and prognosis of SSc-interstitial lung disease. [less ▲]

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See detailHYALURONAN DERIVATIVE HYMOVIS® INCREASES CARTILAGE VOLUME AND TYPE II COLLAGEN TURNOVER IN OSTEOARHRITIC KNEE: DATA FROM MOKHA STUDY
Henrotin, Yves ULiege; Bannuru, Raveendhara R.; Malaise, Michel ULiege et al

in Annals of the Rheumatic Diseases (2018, June), 77(supplement 2), 1614

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See detailEFFICACY OF BIO-OPTIMISED CURCUMA EXTRACT (FLEXOFYTOL®) FOR PAINFUL KNEE OSTEOARTHRITIS: DATA FROM COPRA, A MULTICENTER RANDOMISED CONTROLLED STUDY
Henrotin, Yves ULiege; Malaise, Michel ULiege; Wittoek, R et al

in Annals of the Rheumatic Diseases (2018, June), 77(supplement 2), 790

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See detailSerum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death.
RELIC, Biserka ULiege; CHARLIER, Anne ULiege; DEROYER, Céline ULiege et al

in Oncotarget (2018), 9(88), 35830-35843

Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085 ... [more ▼]

Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085-induced human synovial fibroblast cell death includes autophagy and p62 downregulation. In this work, we have studied expression of P-Ser349 p62 in human synovial fibroblasts. Results showed that P-Ser349 p62 was not detected in synovial cell extracts unless cells were cultured in the presence of proteasome inhibitor (MG132). MG132 revealed P-Ser349 p62 turnover, that was further increased by concomitant autophagy inhibition and markedly enhanced in serum starved cells. Starvation sensitized synovial fibroblasts to BAY 11-7085 while MG132 protected both non-starved and starved cells from BAY 11-7085-induced cell death. Lentivirus mediated overexpression of phosphorylation-mimetic p62 mutant S349E markedly protected synovial fibroblasts from BAY 11-7085. Inhibitor of Keap1-P-S349 p62 interaction, K67, had synergistic effect with MG132. Starvation increased p62 molecular weight, that was reversed by serum and bovine serum albumin re-feeding. Furthermore, starvation markedly induced RAD23B. Increased endo-beta-N-acetylglucosaminidase (ENGase) turnover was detected in starved synovial fibroblasts. PNGase F treatment produced faster migration p62 form in human synovial tissue extracts but starvation-like p62 form of higher molecular weight in synovial cell extracts. Co-transfection of NGLY1, with p62 or p62 mutants S349A and S349E markedly stabilized p62 expressions in HEK293 cells. Tunicamycin upregulated p62 and protected synovial fibroblasts from BAY 11-7085-induced cell death. These results showed that P-Ser349 p62 has pro-survival role in human synovial fibroblasts and that de-glycosylation events are involved in p62 turnover. [less ▲]

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See detailInefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial
HAUZEUR, Jean-Philippe ULiege; De Maertelaer, Viviane ; BAUDOUX, Etienne ULiege et al

in International Orthopaedics (2018), 42

Purpose The fracture stage of non-traumatic osteonecrosis (ON stage 3) of the femoral head (ONFH) has an unfavourable prognosis frequently requiring total hip replacement (THR). The percentage could be ... [more ▼]

Purpose The fracture stage of non-traumatic osteonecrosis (ON stage 3) of the femoral head (ONFH) has an unfavourable prognosis frequently requiring total hip replacement (THR). The percentage could be lowered after core decompression. In earlier non-fracture ON stages, implantation of autologous bone marrow aspirate concentrate (BMAC) improved the effect of core decompression. The purpose was to evaluate the effect of BMAC in addition to core decompression in stage 3 ONFH. Methods A double blind RCT was conducted comparing two groups: core decompression plus saline injection or core decompression plus BMAC implantation. Both patients and assessors were blinded to the treatment assignments. Evaluations were done at baseline, three, six, 12, and 24 months, including pain (VAS), WOMAC, side-effects, radiological evolution including ARCO subclassifications, together with possible THR requirement. The primary endpoint was the need for THR. The second endpoints included the clinical symptoms such as pain and functional ability and the progression of the ON lesions as well as the appearance of osteoarthritis features (ARCO stage 4). Both groups included 23 hips (19 patients). Results No differences were found between the groups for THR requirements, clinical tests, and radiological evolution. In both groups, 15/23 hips needed THR. The radiological evolution of the ONFH lesions in term of location, extension, surface collapse, and dome depression was moderate in both groups and was not correlated with the need of THR. Conclusions Implantation of BMAC after core decompression did not produce any improvement of the evolution of ONFH stage 3. [less ▲]

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See detail(18)F- FDG PET/CT joint assessment of early therapeutic response in rheumatoid arthritis patients treated with rituximab.
Fosse, Pacome; KAISER, Marie-Joëlle ULiege; Namur, Gauthier et al

in European Journal of Hybrid Imaging (2018), 2(1), 6

Background: (18)F-FDG PET/CT has been proposed in the evaluation of the disease activity in rheumatoid arthritis (RA). The goals of this study were to evaluate the reproducibility of the technique, to ... [more ▼]

Background: (18)F-FDG PET/CT has been proposed in the evaluation of the disease activity in rheumatoid arthritis (RA). The goals of this study were to evaluate the reproducibility of the technique, to compare metabolic parameters to clinical, biological and ultrasonographic parameters before and after treatment and to evaluate whether the early metabolic response was related to the outcome. (18)F- FDG PET/CT of the hands, wrists and knees was obtained in 15 patients with anti-TNFalpha refractory RA, at baseline and 16 weeks after treatment with rituximab. The number of PET-positive joints (PET+ joints), the cumulative standard uptake value (cSUV) and the composite index (CI) were defined. The composite clinical index DAS28, CRP serum levels and the number of joints positive at ultrasonography (US+ joints) and the cumulative synovial thickness (CST) were also assessed at baseline and week 24. Results: High interobserver agreement was observed, both at baseline and after treatment. The number of PET+ joints was not correlated with the number of joints tender or swollen. The 3 metabolic parameters were strongly correlated with US, CRP and DAS28 at baseline and with US and CRP (CSUV, CI) at week 16, but no longer with the DAS28 index. The metabolic response based on the change in the visual PET/CT joint analysis predicted the outcome with a high negative predictive value of 91%, with a 91% specificity, and an 86% accuracy. Conclusions: These preliminary data suggest that (18)F- FDG PET/CT is a reproducible and accurate tool for evaluating disease activity in refractory rheumatoid arthritis and its non-response to rituximab. The correlation obtained with US joint assessment gives relevance to objective diseased joints through imaging techniques. [less ▲]

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