J Magdalou

French National Centre for Scientific Research, Lutetia Parisorum, Île-de-France, France

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Publications (241)701.92 Total impact

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    ABSTRACT: UDP-galactose-4-epimerase (GALE) is a key enzyme catalyzing the interconversion of UDP-glucose and UDP-galactose, as well as UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine, which are all precursors for the proteoglycans (PGs) synthesis. However, whether GALE is essential in cartilage homeostasis remains unknown. Therefore, we investigated the role of GALE in PGs synthesis of human articular chondrocytes, the GALE expression in OA, and the regulation of GALE expression by interleukin-1beta (IL-1β). Silencing GALE gene with specific siRNAs resulted in a markedly inhibition of PGs synthesis in human articular chondrocytes. GALE protein levels were also decreased in both human and rat OA cartilage, thus leading to losses of PGs contents. Moreover, GALE mRNA expression was stimulated by IL-1β in early phase, but suppressed in late phase, while the suppression of GALE expression induced by IL-1β was mainly mediated by stress-activated protein kinase/c-Jun N-terminal kinase pathway. These data indicated a critical role of GALE in maintaining cartilage homeostasis, and suggested that GALE inhibition might contribute to OA progress.
    Biochemical and Biophysical Research Communications 09/2014; · 2.28 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) is a chronic joints disease characterized by progressive degeneration of articular cartilage due to the loss of cartilage matrix. Previously, we found, for the first time, that an acidic glycan from Angelica Sinensis Polysaccharides (APSs), namely the APS-3c, could protect rat cartilage from OA due to promoting glycosaminoglycan (GAG) synthesis in chondrocytes. In the present work, we tried to further the understanding of ASP-3c's anti-OA activity.
    PLoS ONE 01/2014; 9(9):e107024. · 3.53 Impact Factor
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    ABSTRACT: Aim:Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat dietMethods:Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies.Results:UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs.Conclusion:PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner.manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.
    Acta Pharmacologica Sinica 11/2013; · 2.35 Impact Factor
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    ABSTRACT: For three decades, low level laser therapy (LLLT) has been used for treatment of tendinitis as well as other musculoskeletal diseases. Nevertheless, the biological mechanisms involved remain not completely understood. In this work, the effects of LLLT and of the widely used nonsteroidal anti-inflammatory drug, diclofenac, have been compared in the case of collagenase-induced Achilles tendinitis. Wistar rats were treated with diclofenac or laser therapy. The tensile behavior of tendons was characterized through successive loading-unloading sequences. The method considered 11 characteristic parameters to describe the mechanical behavior. It was shown that during the acute inflammatory process of the tendon, the mechanical properties were significantly correlated to the high levels of MMP-3, MMP-9 and MMP-13 expression presented in a previous paper (Marcos, R.L., et al., 2012). The treatment by non-steroidal anti-inflammatory drugs such as diclofenac sodium produces a low protective effect and can affect the short-term biochemical and biomechanical properties. On the contrary, it is shown that LLLT exhibits the best results in terms of MMPs reduction and mechanical properties recovery. Thus, LLLT looks to be a promising and consistent treatment for tendinopathies.
    Journal of the mechanical behavior of biomedical materials. 09/2013; 29C:272-285.
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    ABSTRACT: Chondrocalcin is among most highly synthesized polypeptides in cartilage. This protein is released from its parent molecule, type II pro-collagen, after secretion by chondrocytes. A participation of extracellular, isolated chondrocalcin in mineralization was proposed more than 25 years ago, but never demonstrated. Here, exogenous chondrocalcin was found to trigger MMP13 secretion and cartilage destruction ex vivo in human cartilage explants and did so by modulating the expression of interleukin-1β in primary chondrocyte cultures in vitro. Chondrocalcin was found internalized by chondrocytes. Uptake was found mediated by a single 18-mer peptide of chondrocalcin, which does not exhibit homology to any known cell-penetrating peptide. The isolated peptide, when artificially linked as a tetramer, inhibited gene expression regulation by chondrocalcin, suggesting a functional link between uptake and gene expression regulation. At the same time, the tetrameric peptide potentiated chondrocalcin uptake by chondrocytes, suggesting a cooperative mechanism of entry. The corresponding peptide from type I pro-collagen supported identical cell-penetration, suggesting that this property may be conserved among C-propeptides of fibrillar pro-collagens. Structural modelling localized this peptide to the tips of procollagen C-propeptide trimers. Our findings shed light on unexpected function and mechanism of action of these highly expressed proteins from vertebrates.
    Matrix biology: journal of the International Society for Matrix Biology 07/2013; · 3.56 Impact Factor
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    ABSTRACT: Quinolones have been reported to induce adverse effects on articular cartilage, tendons and ligaments. However, the effects of quinolones on menisci have not been revealed. The present study was to test the effects of levofloxacin on meniscus cells in vitro. Rabbit meniscus cells were administrated with different concentrations of levofloxacin (0, 14, 28, 56, 112 and 224 µm) for 24 or 48 h, and cell viability and apoptosis were measured. The mRNA expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-3, Col1a1, Bcl-2, caspase-3 and inducible nitric oxide were analyzed by real-time polymerase chain reaction. Active caspase-3 was detected by immunocytochemical assay, while protein expression levels of MMP-3 and MMP-13 were measured by Western blotting assay. After treatment with levofloxacin for 48 h, cell viability was decreased from dose of 28 to 224 µm in a concentration-dependent manner. An increase of apoptotic cells was observed by flow cytometry. Active caspase-3 protein expression level was also increased. The mRNA level of Bcl-2 was decreased and levels of MMP-1, MMP-3 and MMP-13 in experimental groups were higher than those of controls. The protein levels of MMP-3 and MMP-13 were increased. Moreover, the mRNA levels of TIMP-3 and col1a1 were decreased. A dose-dependent increase of inducible nitric oxide mRNA expression level was also observed. Our results suggested the cytotoxic effects of levofloxacin on meniscus cells through induction of apoptosis and unbalanced MMPs/TIMPs expression. These side effects might result in meniscus extracellular matrix degradation and meniscal lesion. Thus, quinolones should be used cautiously on patients who perform athletic activities or undergo surgical meniscus repair. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 07/2013; · 2.60 Impact Factor
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    ABSTRACT: INTRODUCTION: Sodium ferulate (SF) is a natural component of traditional Chinese herbs. Our previous study shows that SF has a protective effect on osteoarthritis (OA). The objective of this study was to investigate the effect of SF on TNF/TNFR signal transduction pathway of rat OA chondrocytes. METHODS: Primary rat articular chondrocytes were co-treated with interleukin 1 beta (IL-1beta) and SF. Chondrocytes apoptosis was assessed by fluorescein isothiocyanate-Annexin V/propidium iodide assay. The PCR Array was used to screen the expression of 84 key genes involved in apoptosis. The release of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) were analyzed by enzyme linked immunosorbent assay. Expressions of proteins were assessed by Western blotting. The activity of nuclear factor-kappaB was determined by electrophoretic mobility shift assay (EMSA). Gene expression of inducible nitric oxide synthase (iNOS) was evaluated by real-time quantitative PCR. Nitric oxide (NO) content was measured with Griess method. RESULTS: After treatment with SF, apoptosis rate of chondrocytes significantly attenuated (P<0.01). The result of Apoptosis PCR Array suggested that mRNA expression of some core proteins in TNF/TNFR pathway showed valuable regulation. The protein expressions of TNF-alpha, tumor necrosis factor receptor-1 (TNFR-1), TNF receptor-associated death domain (TRADD), caspase-8 and caspase-3 were prevented by SF in the concentration-dependent manner. SF also inhibited activities of caspase-8 and caspase-3 compared with OA model control (P<0.01). TNF receptor-associated factor 2 (TRAF-2) expression, phosphorylations of inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKalpha), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKbeta) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkappaBalpha) were all concentration-dependently suppressed by SF treatment. The result of EMSA showed that SF inhibited the activity of nuclear factor-kappaB. In addition, the expressions of cycloxygenase 2 and iNOS, and the contents of PGE2 and NO were attenuated with the treatment of SF (P<0.01). CONCLUSIONS: SF has anti-apoptosis and anti-inflammatory effects on OA model induced by IL-1beta in vitro, which were due to the inhibitory actions on caspase-dependent apoptosis pathway and IKK/NF-kappaB signal transduction pathway of TNF/TNFR pathway.
    Arthritis research & therapy 05/2013; 15(3):407. · 4.27 Impact Factor
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    ABSTRACT: Nacre (or mother of pearl) can facilitate bone cell differentiation and can speed up their mineralization. Here we report on the capability of nacre to induce differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) and the production of extracellular matrix. hBM-MSCs were encapsulated in an alginate hydrogel containing different concentrations of powdered nacre and cultured in the same environment until Day 28. Analysis of osteogenic gene expression, histochemistry, second harmonic generation (SHG) microscopy, and Raman scattering spectroscopy were used to characterize the synthesis of the extracellular matrix. In the presence of nacre powder, a significant increase in matrix synthesis from D21 in comparison with pure alginate was observed. Histochemistry revealed the formation of a new tissue composed of collagen fibers in the presence of nacre (immunostaining and SHG), and hydroxyapatite crystals (Raman) in the alginate beads. These results suggest that nacre is efficient in hBM-MSCs differentiation, extracellular matrix production and mineralization in alginate 3D biomaterials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
    Journal of Biomedical Materials Research Part A 04/2013; · 2.83 Impact Factor
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    Toxicology Letters 03/2013; 218(1):1. · 3.15 Impact Factor
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    ABSTRACT: Cucurbitacin E (Cuc E), highly oxygenated triterpene from cucurbitaceae family, was demonstrated to possess anti-proliferative, anti-inflammatory and anti-oxidant activities. Here, we studied the effect of Cuc E on the properties of the phospholipid membrane. Large unilamellar vesicles, with and without sulforhodamine B (SRB), were prepared in the absence and presence of Cuc E. The fluorescence increase, resulting from SRB release from vesicles due to inhibition of auto-quenching, was used to assess the permeability of liposome at 4° and 37°C. At 4°C, blank liposomes and those containing Cuc E were stable; while at 37°C Cuc E loaded liposomes showed less stability than blank ones. The loading efficiency of Cuc E into the vesicles was demonstrated to be 85% by HPLC. Dynamic light scattering measurements showed that liposomes embedding Cuc E were smaller than those which did not. Multilamellar vesicles were manufactured from dipalmitoylphosphatidylcholine in the presence and absence of Cuc E (molar ratio 7%). Results obtained by differential scanning calorimetry suggest that Cuc E binds mainly at the polar/apolar interfacial region of lipid bilayers and may incorporate into the lipid bilayer. Cuc E does not produce phase separation and thus might be included in liposome formulation.
    International Journal of Pharmaceutics 03/2013; · 3.99 Impact Factor
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    ABSTRACT: Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0mg/kg.d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100μM of nicotine for 10days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis.
    Toxicology and Applied Pharmacology 02/2013; · 3.98 Impact Factor
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    ABSTRACT: To better understand the factors that contribute to the accumulation of unmetabolized parabens (p-hydroxybenzoic acid esters) in breast cancer tissue, we investigated the binding of a series of parabens (methyl-, ethyl-, butyl-, benzyl-paraben) to human serum albumin (HSA) by fluorescence spectroscopy and their ability to modify the binding parameters of albumin site markers. Emission spectra of HSA upon fluorescence excitation of Trp 214 residue at 295 nm were recorded at different molar ratios PB/HSA and data was corrected for the inner-filter effect. Significant inner-filter effect was obtained from molar ratios 2.0 and above. For lower molar ratios, a slight increase in fluorescence of HSA was detected. p-Hydroxybenzoic acid, the main metabolite of parabens, did not modify the fluorescence of HSA whatever the molar ratio used. Binding parameters for compounds that are markers of site I, bilirubin and warfarin, were determined in the absence and presence of methyl, butyl and benzyl paraben at molar ratios PB/HSA: 0, 1 and 2. No variation of the binding constants of these markers was observed. Our results indicate that parabens weakly interact with HSA thus suggesting that they are as a free form in blood and therefore more available to reach tissues. Copyright © 2013 John Wiley & Sons, Ltd.
    Biopharmaceutics & Drug Disposition 01/2013; · 2.09 Impact Factor
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    ABSTRACT: This study investigated the effect of Angelica sinensis polysaccharides (APS-3c) on rat osteoarthritis (OA) model in vivo and rat interleukin-1-beta- (IL-1 β -) stimulated chondrocytes in vitro. APS-3c was administrated into rat OA knee joints and had protective effects on rat OA cartilage in vivo. Primary rat articular chondrocytes were cotreated with APS-3c and IL-1 β in vitro. 2~50 μ g/mL APS-3c had no effect on chondrocytes viability, whereas it increased the proteoglycans (PGs) synthesis inhibited by IL-1 β . Microarray analysis showed that the significant changes were concentrated in the genes which were involved in PGs synthesis. RT-PCR confirmed that treatment with APS-3c increased the mRNA expression of aggrecan and glycosyltransferases (GTs) inhibited by IL-1 β but did not affect the mRNA expression of matrix-degrading enzymes. These results indicate that APS-3c can improve PGs synthesis of chondrocytes on rat OA model in vivo and IL-1 β -stimulated chondrocytes in vitro, which is due to the promotion of the expression of aggrecan and GTs involved in PGs synthesis but not the inhibition of the expression of matrix-degrading enzymes. Our findings suggest the clinical relevance of APS-3c in the prospective of future alternative medical treatment for OA.
    Evidence-based Complementary and Alternative Medicine 01/2013; 2013:794761. · 1.72 Impact Factor
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    ABSTRACT: Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”.
    Toxicology and Applied Pharmacology 01/2013; · 3.98 Impact Factor
  • Article: Foreword.
    J Magdalou, J F Stoltz, P Netter, A Pinzano
    Bio-medical materials and engineering 01/2013; 23(4):249. · 1.09 Impact Factor
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    ABSTRACT: Xylosyltransferase I (XT-I) is an essential enzyme of proteoglycan (PG) biosynthesis pathway catalyzing the initial and rate-limiting step in glycosaminoglycan chain assembly. It plays a critical role in the regulation of PG synthesis in cartilage, however little is known about underlying mechanism. Here, we provide evidence that, in human primary chondrocytes, IL-1β regulates XT-I gene expression into an early phase of induction and a late phase of down-regulation. Based on promoter deletions, the region up to -850 bp was defined as a major element of XT-I gene displaying both constitutive and IL-1β-regulated promoter activity. Point mutation and signalling analyses revealed that IL-1β-induced promoter activity is achieved through AP-1 response elements and mediated by SAP/JNK and p38 signalling pathways. Transactivation and chromatin immunoprecipitation assays indicated that AP-1 is a potent transactivator of XT-I promoter and that IL-1β-induced activity is mediated through increased recruitment of AP1 to the promoter. Finally, we show that Sp3 is a repressor of XT-I promoter and bring evidence that the repressive effect of IL-1β during the late phase is mediated through Sp3 recruitment to the promoter. This suggests that modulation of Sp3 in cartilage could prevent IL-1β inhibition of PG synthesis and limit tissue degradation.
    Journal of Biological Chemistry 12/2012; · 4.65 Impact Factor

Publication Stats

3k Citations
701.92 Total Impact Points


  • 1997–2014
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 2012–2013
    • University of Lorraine
      Nancy, Lorraine, France
    • Lebanese University
      • Doctorate School of Science and Technology
      Beirut, Mohafazat Beyrouth, Lebanon
  • 2010–2013
    • Wuhan University
      • Department of Pharmacology
      Wuhan, Hubei, China
  • 2009
    • Holy Spirit University of Kaslik
      Beyrouth, Beyrouth, Lebanon
  • 2007
    • Université Victor Segalen Bordeaux 2
      Burdeos, Aquitaine, France
  • 1993–2005
    • University of Arkansas at Little Rock
      Little Rock, Arkansas, United States
  • 2004
    • University of Arkansas for Medical Sciences
      Little Rock, Arkansas, United States
    • HCL
      Noida, Uttar Pradesh, India
  • 1987–1996
    • Centre Hospitalier Universitaire de Nancy
      Nancy, Lorraine, France
  • 1988–1993
    • University of California, Davis
      • • Department of Environmental Toxicology
      • • Department of Entomology
      Davis, CA, United States
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 1990
    • University of Burgundy
      Dijon, Bourgogne, France