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1. List of contributors

Author

Afonso, Ana Beatriz, primary, Amaral, Robson, additional, Andrade, Luciana N., additional, Assalin, Heloisa Balan, additional, Bastos, Reinaldo Gaspar, additional, Baugé, Catherine, additional, Beg, Sarwar, additional, Bíscaro, Gabriel Gaspar, additional, Bonde, S., additional, Bonilla-Vidal, Lorena, additional, Boonme, P., additional, Boumediene, Karim, additional, Caliari-Oliveira, Carolina, additional, Cano, Amanda, additional, Capasso, Raffaele, additional, Carbone, Claudia, additional, Cardoso (J.C. Cardoso), Juliana C., additional, Chaud (Marco V. Chaud), Marco Vinicius, additional, Clares, Beatriz, additional, Costa, Maria C., additional, Coutinho, Tiago E., additional, Cruz, Ana T., additional, da Silva, Classius F., additional, de Albuquerque-Júnior, Ricardo L.C., additional, de Hollanda, Luciana M., additional, de Melo (B.A.G. de Melo), Bruna Alice G., additional, de Oliveira, Alexandre Leite Rodrigues, additional, de Souza, Alexandro Barbosa, additional, Dias-Ferreira, J., additional, dos Santos, Andrey, additional, Durán, Nelson, additional, Durazzo, Alessandra, additional, Eder, Piotr, additional, Espina, Marta, additional, Esteruelas, Gerard, additional, Fávaro, Wagner J., additional, Formiga, Fabio Rocha, additional, Formoso, Inês, additional, França, Carla G., additional, Gálvez, Patricia, additional, García, María Luisa, additional, Garrido, María T., additional, Hammad, Mira, additional, Handa, Mayank, additional, Huber, Stephany C., additional, Jovanovic, J., additional, Kamalov, Marat I., additional, Kovačevi, Anðelka, additional, Lana, José Fabio S.D., additional, Leme, Krissia Caroline, additional, Lima, Daniele M., additional, Lucarini, Massimo, additional, Luzo (Ângela Cristina M. Luzo), Ângela Cristina Malheiros, additional, Manfiolli, Adriana Oliveira, additional, Masson, Patrick, additional, Mercier Franco, Luis Fernando, additional, Moravkar, Kailas Kalicharan, additional, Nobre, Joana, additional, Pardeshi, Chandrakantsing Vijaysing, additional, Pashirova, Tatiana N., additional, Patel, M., additional, Patel, R., additional, Pawar, Jaywant, additional, Pessoa Filho, Pedro de Alcântara, additional, Rai, M., additional, Ríos, Manuel, additional, Sánchez López, Elena, additional, López, Elena, additional, Santana (Maria H. Santana), Maria Helena A., additional, Santini, Antonello, additional, Severino (P. Severino), Patrícia, additional, Shegokar, Ranjita, additional, Shimojo, Andrea A.M., additional, Shingare, Dilip Waman, additional, Shukla, Rahul, additional, Silva, Amélia M., additional, Singh, K.K., additional, Soni, Mukesh, additional, Soriano, José L., additional, Souto, Eliana B., additional, Tambeli, Claudia Herrera, additional, Teixeira, M.C., additional, Terekhova, Natalia V., additional, and Zielinska (A. Zielińska), Aleksandra, additional

Published
2023
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2. Platelet-rich plasma, their growth factors, cytokines and clinical use

Author

Luzo, Ângela Cristina Malheiros, primary, Leme, Krissia Caroline, additional, Fávaro, Wagner J., additional, Durán, Nelson, additional, Bíscaro, Gabriel Gaspar, additional, de Oliveira, Alexandre Leite Rodrigues, additional, Boumediene, Karim, additional, Hammad, Mira, additional, and Baugé, Catherine, additional

Published
2023
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3. Bioactive Compounds in Osteoarthritis: Molecular Mechanisms and Therapeutic Roles.

Author

Maouche, Ahmed, Boumediene, Karim, and Baugé, Catherine

Subjects
JOINT pain, GINGER, TEA extracts, PLANT extracts, INFLAMMATION
Abstract

Osteoarthritis (OA) is the most common and debilitating form of arthritis. Current therapies focus on pain relief and efforts to slow disease progression through a combination of drug and non-drug treatments. Bioactive compounds derived from plants show significant promise due to their anti-inflammatory, antioxidant, and tissue-protective properties. These natural compounds can help regulate the inflammatory processes and metabolic pathways involved in OA, thereby alleviating symptoms and potentially slowing disease progression. Investigating the efficacy of these natural agents in treating osteoarthritis addresses a growing demand for natural health solutions and creates new opportunities for managing this increasingly prevalent age-related condition. The aim of this review is to provide an overview of the use of some bioactive compounds from plants in modulating the progression of osteoarthritis and alleviating associated pain. [ABSTRACT FROM AUTHOR]

Published
2024
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4. A single intraarticular injection of a tranexamic acid-modified hyaluronic acid (HA/TXA) alleviates pain and reduces OA development in a murine model of monosodium iodoacetate-induced osteoarthritis.

Author

Brochard, Sybille, Boumédiene, Karim, Mercier, Jéromine, Agin, Véronique, Conrozier, Thierry, and Baugé, Catherine

Subjects
INTRA-articular injections, PLASMINOGEN activator inhibitors, TRANEXAMIC acid, HYALURONIC acid, ANIMAL experimentation, KNEE
Abstract

Rationale: Tranexamic acid (TXA) is a strong and specific plasminogen activator inhibitor with inhibitory effects on the matrix metalloproteases involved in the pathophysiology of osteoarthritis (OA) through targeting of the fibrinolysis pathway. In this study, we evaluated the analgesic and chondroprotective effects of a HA-tranexamic acid (HA/TXA) conjugate, compared to HA alone and placebo, in an animal model of knee OA. Methods: Knee OA was induced in 15 C57 b l/6J mice by IA injection of 0.75 mg of Monosodium IodoAcetate (MIA). At day 28, the mice received 1 IA injection of 10 µL of saline (control-group), or of HA or of HA/TXA. Tactile sensitivity was assessed using von Frey filaments. Stimulations started at 1 g and increased until a response was obtained (up to 4 g). A response to the stimulus was counted if the animal withdrew its paw. If the animal responded to the 1 g stimulation, stimulation was reduced until the lack of response was observed (up to 0.2 g). At day 56, mice were euthanized for knee histological assessment. Cartilage degradation was assessed using the OARSI score. Statistical analysis was performed on GraphPad Prism 8.0.2 software. Kruskal-Wallis or Mann-Whitney tests were performed as appropriate. Results: Just before treatment administration, no intergroup difference in paw withdrawal threshold was observed. Throughout the experiment animals given saline and HA had a lower paw withdrawal threshold than those treated with HA/TXA (p < 0.01). In the control group OARSI score was 5.5 ± 0.6. In HA and HA + TXA treated mice the OARSI score was 3.2 ± 0.8 and 3.1 ± 0.5 (p < 0.01) showing that both treatments were able to reduce OA progression. Conclusion: In this animal model of MIA induced KOA, a single IA injection of a HA/TXA conjugate resulted in a greater efficacy on pain than both saline and HA. HA and HA/TXA exhibited chondroprotective effects compared to placebo. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Modulation of transforming growth factor beta signalling pathway genes by transforming growth factor beta in human osteoarthritic chondrocytes: involvement of Sp1 in both early and late response cells to transforming growth factor beta

Author

Baugé, Catherine, Cauvard, Olivier, Leclercq, Sylvain, Galéra, Philippe, and Boumédiene, Karim

Subjects
Quantitative Biology - Tissues and Organs
Abstract

Transforming growth factor beta (TGF$\beta$) plays a central role in morphogenesis, growth, and cell differentiation. This cytokine is particularly important in cartilage where it regulates cell proliferation and extracellular matrix synthesis. While the action of TGF$\beta$ on chondrocyte metabolism has been extensively catalogued, the modulation of specific genes that function as mediators of TGF$\beta$ signalling is poorly defined. In the current study, elements of the Smad component of the TGF$\beta$ intracellular signalling system and TGF$\beta$ receptors were characterised in human chondrocytes upon TGF$\beta$1 treatment. Human articular chondrocytes were incubated with TGF$\beta$1. Then, mRNA and protein levels of TGF$\beta$ receptors and Smads were analysed by RT-PCR and western blot analysis. The role of specific protein 1 (Sp1) was investigated by gain and loss of function (inhibitor, siRNA, expression vector). We showed that TGF$\beta$1 regulates mRNA levels of its own receptors, and of Smad3 and Smad7. It modulates TGF$\beta$ receptors post-transcriptionally by affecting their mRNA stability, but does not change the Smad-3 and Smad-7 mRNA half-life span, suggesting a potential transcriptional effect on these genes. Moreover, the transcriptional factor Sp1, which is downregulated by TGF$\beta$1, is involved in the repression of both TGF$\beta$ receptors but not in the modulation of Smad3 and Smad7. Interestingly, Sp1 ectopic expression permitted also to maintain a similar expression pattern to early response to TGF$\beta$ at 24 hours of treatment. It restored the induction of Sox9 and COL2A1 and blocked the late response (repression of aggrecan, induction of COL1A1 and COL10A1). These data help to better understand the negative feedback loop in the TGF$\beta$ signalling system, and enlighten an interesting role of Sp1 to regulate TGF$\beta$ response.

Published
2015
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6. Asporin expression is highly regulated in human chondrocytes

Author

Duval, Elise, Bigot, Nicolas, Hervieu, Magalie, Kou, Ikuyo, Leclercq, Sylvain, Galéra, Philippe, Boumediene, Karim, and Baugé, Catherine

Subjects
Quantitative Biology - Tissues and Organs
Abstract

A significant association between a polymorphism in the D repeat of the gene encoding asporin and osteoarthritis, the most frequent of articular diseases, has been recently reported. The goal of the present study was to investigate the expression of this new class I small leucine-rich proteoglycan (SLRP) in human articular chondrocytes. First, we studied the modulation of asporin (ASPN) expression by cytokines by Western blot and reverse transcription-polymerase chain reaction. Interleukin-1$\beta$ and tumor necrosis factor-$\alpha$ downregulated ASPN, whereas transforming growth factor-$\beta$1 (when incubated in a serum-free medium) upregulated it. Similarly to proinflammatory cytokines, chondrocyte dedifferentiation induced by a successive passages of cells was accompanied by a decreased asporin expression, whereas their redifferentiation by three-dimensional culture restored its expression. Finally, we found an important role of the transcription factor Sp1 in the regulation of ASPN expression. Sp1 ectopic expression increased ASPN mRNA level and promoter activity. In addition, using gene reporter assay and electrophoretic mobility shift assay, we showed that Sp1 mediated its effect through a region located between -473 and -140 bp upstream of the transcription start site in ASPN gene. In conclusion, this report is the first study on the regulation of asporin expression by different cytokines in human articular chondrocytes. Our data indicate that the expression of this gene is finely regulated in cartilage and suggest a major role of Sp1.

Published
2015
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15. Description of Joint Alterations Observed in a Family Carrying p.Asn453Ser COMP Variant: Clinical Phenotypes, In Silico Prediction of Functional Impact on COMP Protein and Stability, and Review of the Literature

Author

Rochoux, Quitterie, primary, Sopkova-de Oliveira Santos, Jana, additional, Marcelli, Christian, additional, Rovelet-Lecrux, Anne, additional, Chevallier, Virginie, additional, Dutheil, Jean-Jacques, additional, Leclercq, Sylvain, additional, Boumédiene, Karim, additional, Baugé, Catherine, additional, and Aury-Landas, Juliette, additional

Published
2021
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21. Cell-penetrating, antioxidant SELENOT mimetic protects dopaminergic neurons and ameliorates motor dysfunction in Parkinson's disease animal models

Author

Alsharif, Ifat, primary, Boukhzar, Loubna, additional, Lefranc, Benjamin, additional, Godefroy, David, additional, Aury-Landas, Juliette, additional, Rego, Jean-Luc do, additional, Rego, Jean-Claude do, additional, Naudet, Frédéric, additional, Arabo, Arnaud, additional, Chagraoui, Abdeslam, additional, Maltête, David, additional, Benazzouz, Abdelhamid, additional, Baugé, Catherine, additional, Leprince, Jérôme, additional, Elkahloun, Abdel G., additional, Eiden, Lee E., additional, and Anouar, Youssef, additional

Published
2021
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22. Evaluation of the impact of S-adenosylmethionine-dependent methyltransferase inhibitor, 3-deazaneplanocin A, on tissue injury and cognitive function in mice

Author

Lhuissier, Eva, Aury-Landas, Juliette, BouËt, Valentine, Bazille, Céline, Repesse, Yohann, Freret, Thomas, Boumediene, Karim, Baugé, Catherine, Université de Caen Normandie (UNICAEN), Normandie Université (NU), Biotechnologie des tissus conjonctifs et cutanés / Biology of Connective and Cutaneous Tissues (BioConnecT), Normandie Université (NU)-Normandie Université (NU), Groupe Mémoire et Plasticité comportementale (GMPc), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Etablissement français du sang - Normandie (EFS), Laboratoire d'Hématologie Biologique [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), ANR-15-CE14-0002,EpiCart,Methylation de l'histone H3K27 : régulation et rôle dans le cartilage articulaire(2015), Baugé, Catherine, Methylation de l'histone H3K27 : régulation et rôle dans le cartilage articulaire - - EpiCart2015 - ANR-15-CE14-0002 - AAPG2015 - VALID, and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, cognitive functions, antitumoral drug, toxicity, epigenetic, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Paper
Abstract

International audience; Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients' quality of life. The aim of this study was to investigate the toxicity of 3-Deazaneplanocin A (DZNep) on several tissues and organs, as well as on cognitive functions. DZNep is an inhibitor of S-adenosylmethionine-dependent methyltransferase (in particular of the histone methyltransferase EZH2) which showed antitumoral functions in preclinical trials but whose effects on behavior and on organs (side effects) are not known. Chronic injections of DZNep were performed intraperitoneally in male NMRI mice (2 mg/kg; i.p.; three times per week) during 8 weeks. A follow-up of body weight was assessed during all experiments. Histological analysis were performed on several organs. EZH2 expression and H3K27me3 were assayed by western-blot. Several behavioral tests were performed during treatment and 2 weeks after. A particular focus was made on spontaneous locomotor activity, cognitive functions (spontaneous alternation and recognition memory), and anxiety- and depression-related behavior. Hematological modifications were also assessed. Chronic DZNep treatment transiently reduced animal growth. It had no effect on most organs but provoked a reversible splenomegaly, and persistent testis reduction and erythropoiesis. DZNep administration did not alter animal behavior. In conclusion, this study is encouraging for the use of DZNep for cancer treatment. Indeed, it has no effect on animal behavior, conferring an advantageous safety, and induces irreversible side effects limited on testis which are unfortunately found in most chemotherapy treatments.

Published
2018
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23. Identification of an easy to use 3D culture model to investigate invasion and anticancer drug response in chondrosarcomas

Author

Lhuissier, Eva, Bazille, Céline, Aury-Landas, Juliette, Girard, Nicolas, Pontin, Julien, Boittin, Martine, Boumediene, Karim, Baugé, Catherine, Normandie Université (NU), Biotechnologie des tissus conjonctifs et cutanés / Biology of Connective and Cutaneous Tissues (BioConnecT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), and Ligue contre le Cancer

Subjects
musculoskeletal diseases, Alginates, Cell Survival, [SDV]Life Sciences [q-bio], Chondrosarcomas, Cell Culture Techniques, Chondrosarcoma, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 3 dimensional culture, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:RC254-282, Hydrogel, Polyethylene Glycol Dimethacrylate, Mice, Glucuronic Acid, Cell Line, Tumor, Animals, Humans, Cell Proliferation, Cancer, Hexuronic Acids, Alginate, Antitumoral drug, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Xenograft Model Antitumor Assays, Cisplatin, Research Article
Abstract

International audience; Background Cytotoxic efficacy of anticancer drugs has been widely studied with monolayer-cultured cancer cells. However, the efficacy of drugs under two-dimensional (2D) culture condition usually differs from that of three-dimensional (3D) one. In the present study, an in vitro tumor tissue model was constructed using alginate hydrogel, and in vitro cytotoxic efficacy of two anticancer drugs (cisplatin and DZNep) was investigated in chondrosarcomas, and compared to in vivo response. Methods Three cell lines derived from human chondrosarcomas, CH2879, JJ012 and SW1353, were embedded in alginate hydrogel. Proliferation and survival were assayed by ATP measurement using Cell Titer-Glo luminescent cell viability assay kit, and by counting viable cells in beads. Collagen and COMP expression was determined by RT-PCR. Invasion/migration was estimated by counting cells leaving alginate beads and adhering to culture dish. Then, chondrosarcoma response to cisplatin and DZNep was compared between cells cultured in monolayer or embedded in alginate, and using chondrosarcoma xenografts in nude mice. Results Chondrosarcomas survived at least for 8 weeks, after embedment in alginate. However, only CH2879 cells could proliferate. Also, this cell line is more invasive than SW1353 and JJ012, which was coherent with the grade of their respective primary tumors. Furthermore, the expression of type II collagen was higher in chondrosarcomas cultured in 3D than in 2D. Interestingly, this 3D culture system allows to validate the absence of response of chondrosarcomas to cisplatin, and to predict the efficiency of DZNep to reduce chondrosarcoma growth in vivo. Conclusions This study validates alginate beads as a relevant 3D model to study cancer biology and tumor responses to biological treatments.

Published
2017
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24. The Antitumoral Effect of the S-Adenosylhomocysteine Hydrolase Inhibitor, 3-Deazaneplanocin A, is Independent of EZH2 but is Correlated with EGFR Downregulation in Chondrosarcomas

Author

Aury-Landas, Juliette, Girard, Nicolas, Lhuissier, Eva, Adouane, Drifa, Delépée, Raphaël, Boumediene, Karim, Baugé, Catherine, Biotechnologie des tissus conjonctifs et cutanés / Biology of Connective and Cutaneous Tissues (BioConnecT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Interactions Cellules Organismes Environnement (ICORE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Région Basse-Normandie, Ligue Contre le Cancer, and Cancéropôle Nord-Ouest

Subjects
musculoskeletal diseases, Male, Adenosine, Cell Survival, EGFR, Chondrosarcomas, Transcriptomic Analysis, Chondrosarcoma, Histone methylase, Down-Regulation, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, Bone Neoplasms, lcsh:Physiology, lcsh:Biochemistry, Histones, Mice, Cell Line, Tumor, Bone tumors, Animals, Humans, lcsh:QD415-436, Enhancer of Zeste Homolog 2 Protein, Protein Interaction Maps, RNA, Small Interfering, S-adenosylmethionine, lcsh:QP1-981, musculoskeletal system, S-Adenosylhomocysteine, ErbB Receptors, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, RNA Interference, Gene expression, Drug, DNA Damage
Abstract

International audience; Background/Aims: 3-Deazaneplanocin, DZNep, has been reported to inhibit the EZH2 histone methylase and to induce cell apoptosis in chondrosarcomas (CS). The present study aims to confirm the therapeutic potential of EZH2 inhibitors and investigate the molecular mechanisms of DZNep in chondrosarcomas.Methods: CS cell lines and primary cultures were used. Apoptosis was investigated using PARP cleavage, caspase 3/7 activity, or Apo2.7 expression. S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were quantified by UHPLC-MS/MS. Differentially expressed genes in treated-chondrosarcomas and chondrocytes were researched by microarray analysis.Results: DZNep induced apoptosis in chondrosarcomas both in vivo and in vitro. However, this effect was not correlated to EZH2 expression nor activity, and EZH2 knock-down by siRNA did not reduce CS viability. Additionally, the reduction of H3K27me3 induced by GSK126 or tazemetostat (EPZ-6438) did not provoke chondrosarcoma death. However, as expected, DZNep induced SAH accumulation and reduced SAM:SAH ratio. Further, microarray analysis suggests a key role of EGFR in antitumoral effect of DZNep, and pharmacological inhibition of EGFR reduced chondrosarcoma survival.Conclusion: EZH2 is not an adequate target for chondrosarcoma treatment. However, DZNep induces apoptosis in chondrosarcomas in vitro and in vivo, by a mechanism likely mediated though EGFR expression. Consequently, it would be worth initiating clinical trials to evaluating efficiency to S-adenosylhomocysteine hydrolase or EGFR inhibitors in patients with chondrosarcomas.

Published
2019
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26. Bénéfice d un copolymère injectable d'acides gras dans le traitement des maladies articulaires

Author

Baugé , Catherine, Ewert , Gérard, Aury-Landas , Juliette, Berthelot , Marion, Boumediene , Karim, Devaux , Emmanuel, Biotechnologie des tissus conjonctifs et cutanés / Biology of Connective and Cutaneous Tissues ( BioConnecT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Normandie Université ( NU ), Sexmoor, Biotechnologie des tissus conjonctifs et cutanés / Biology of Connective and Cutaneous Tissues (BioConnecT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), and Baugé, Catherine

Subjects
Inflammation, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [ SDV ] Life Sciences [q-bio], [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Arthritis, [SDV]Life Sciences [q-bio], Extracellular matrix, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Fatty acid, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Osteoarthritis, Cytokines, Joints, Drug therapy, Gene expression, MMPs, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract

METHODS. Inflammation was mimicked in vitro by treatment of human articular chondrocytes with interleukin-1β, and in synoviocytes with LPS. Effects of a treatment with a copolymer of fatty acids (ara 3000 beta®) were determined by evaluating MMP production by RT-PCR and ELISA, NO release by Griess assay, and PGE2 expression by ELISA. In addition, in vivo analysis (evolution of weight and edema) were also performed after injection of Freund adjuvant in rats.RESULTS. The copolymer of fatty acids clearly reduced inflammation in joint. In vitro, it impaired IL1 stimulated-MMP production and release, as well as release of NO and PGE2 and activation of NFκB in chondrocytes. Also, in synoviocytes, it reduces the induction of MMP and IL-6. Furthermore, in vivo experiments corroborate the anti-inflammatory effects of ara 3000 beta®, with a reduction of edema, erythema and ankylosis in arthritic rats.CONCLUSION. The results support the hypothesis that a copolymer of fatty acids, such as ara 3000 beta® has anti-inflammatory properties, suggesting a beneficial potential for preventing cartilage degradation associated with chronic inflammatory joint diseases., MÉTHODOLOGIE. Une étude in vitro et in vivo a évalué les effets d’un traitement avec un copolymère d’acides gras (ara 3000 beta®) sur une inflammation des chondrocytes et des synoviocytes.RÉSULTATS. Le copolymère d’acides gras réduit nettement l’inflammation dans l’articulation. In vitro, il limite la production des métalloprotéases matricielles et de l’interleukine 6, la sécrétion d’oxyde nitrique et de prostaglandine E2 et l’activation de NFκB. In vivo, l’ara 3000 beta® diminue l’oedème, l’érythème et l’ankylose.CONCLUSION. Les résultats de cette étude suggèrent qu’un copolymère d’acides gras possède des propriétés antiinflammatoires et freine la dégradation du cartilage associée aux maladies articulaires inflammatoires chroniques

Published
2017

30. Hypoxia inducible factor 1 alpha down-regulates type i collagen through Sp3 transcription factor in human chondrocytes

Author

Duval, Elise, Bouyoucef, Mouloud, Leclercq, Sylvain, Baugé, Catherine, Boumediene, Karim, Normandie Université (NU), Microenvironnement et Pathologies du Cartilage (BioConnecT), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and Federation Hospitalo-Universitaire SURFACE

Subjects
musculoskeletal diseases, hypoxia, [SDV]Life Sciences [q-bio], collagen type I, chondrocytes, Gene Expression Regulation, Developmental, Cell Differentiation, Genetic Therapy, Hypoxia-Inducible Factor 1, alpha Subunit, hypoxia-inducible factor 1, Collagen Type I, alpha 1 Chain, Sp3 Transcription Factor, gene expression, Humans, Promoter Regions, Genetic, cartilage, Cartilage Diseases, Sp transcription factors
Abstract

Cartilage engineering is one challenging issue in regenerative medicine. Low oxygen tension or hypoxia inducible factor-1 (HIF-1α) gene therapy are promising strategies in the field of cartilage repair. Previously, we showed that hypoxia and its mediator HIF-1 regulate matrix genes expression (collagens and aggrecan). Here, we investigated the molecular mechanism involved in the regulation of type I collagen (COL1A1) by HIF-1 in human articular chondrocytes. We show that HIF-1α reduces COL1A1 transcription, through a distal promoter (-2300 to -1816 bp upstream transcription initiation site), containing two GC boxes that bind Sp transcription factors (Sp1/Sp3). Sp1 acts as a positive regulator but is not induced by HIF-1. COL1A1 inhibition caused by HIF-1 implies only Sp3, which accumulates and competes Sp1 binding on COL1A1 promoter. Additionally, Sp3 ectopic expression inhibits COL1A1, while Sp3 knockdown counteracts the downregulation of COL1A1 induced by HIF-1. In conclusion, we established a new regulatory model of COL1A1 regulation by HIF-1, and bring out its relationship with Sp3 transcription factor. In a fundamental level, these findings give insights in the mechanisms controlling COL1A1 gene expression. This may be helpful to improve strategies to impair type I collagen expression during chondrocyte differentiation for cartilage engineering. © 2016 IUBMB Life, 68(9):756-763, 2016.

Published
2016
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32. Molecular characterization of commonly used chondrosarcoma cell lines

Author

Aury-Landas, Juliette, Barreau, Morgane, Girard, Nicolas, Lhuissier, Eva, Boumediene, Karim, Baugé, Catherine, Normandie Université ( NU ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Normandie Université (NU), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, ComputingMilieux_MISCELLANEOUS, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract

International audience

Published
2015

33. Missing heritability in primary osteoarthritis: the Exorhum project

Author

Baugé, Catherine, Aury-Landas, Juliette, Leclercq, Sylvain, Marcelli, Christian, Boumediene, Karim, Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), Service de Rhumatologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

34. Thérapie épigénétique avec le 3-deazaneplanocin (DZNep), un inhibiteur de l'histone méthyl-tranférase EZH2, traitement futur des chondrosarcomes de haut grade ?

Author

Bazille, Céline, Girard, Nicolas, Boumediene, Karim, Baugé, Catherine, Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and CHU de Caen

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2015

35. Use of Adult Stem Cells for Cartilage Tissue Engineering: Current Status and Future Developments

Author

Baugé, Catherine and Boumédiene, Karim

Subjects
Article Subject
Abstract

Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. So, in recent years, researchers and surgeons have been working hard to elaborate cartilage repair interventions for patients who suffer from cartilage damage. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or hypertrophic cartilage. In the next years, the development of new strategies using adult stem cells, in scaffolds, with supplementation of culture medium and/or culture in low oxygen tension should improve the quality of neoformed cartilage. Through these solutions, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injury or chondropathies. This review discusses the current knowledge about the use of adult stem cells in the context of cartilage tissue engineering and presents clinical trials in progress, as well as in the future, especially in the field of bioprinting stem cells.

Published
2015
Full Text
View/download PDF

36. Comparative study of the sensibility of chondrosarcoma to DNA damaging agents

Author

Girard, Nicolas, Lhuissier, Eva, Cauvard, Olivier, Batalla, A., Bazille, Céline, Boumediene, Karim, Baugé, Catherine, Normandie Université (NU), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

37. Epigenetic therapy; a promising treatment for chondrosarcoma?

Author

Girard, Nicolas, Bazille, Céline, Lhuissier, Eva, Benateau, Hervé, Boumediene, Karim, Baugé, Catherine, Normandie Université (NU), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Chirurgie Maxillo-Faciale, Plastique et Reconstructrice, Chirurgie Orale et implantologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

38. Epigenetic therapy: a treatment for chondrosarcoma ?

Author

Girard, Nicolas, Bazille, Céline, Lhuissier, Eva, Benateau, Hervé, Boumediene, Karim, Baugé, Catherine, Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Chirurgie Maxillo-Faciale, Plastique et Reconstructrice, Chirurgie Orale et implantologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

39. Comparative study of chondrosarcomas response to DNA damage. Impact of HIF2 expression

Author

Lhuissier, Eva, Girard, Nicolas, Cauvard, Olivier, Bazille, Céline, Bénateau, Hervé, Batalla, A., Llombart-Bosch, Antonio, Baugé, Catherine, Boumediene, Karim, Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Chirurgie Maxillo-Faciale, Plastique et Reconstructrice, Chirurgie Orale et implantologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Valencia, and EACR

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

40. 3-deazaneplanocin A (DZNep), an inhibitor of histone methyltransferase EZH2, induces apoptosis and reduces cell migration in chondrosarcoma cells

Author

Girard, Nicolas, Bazille, Céline, Lhuissier, Eva, Benateau, Hervé, Llombart-Bosch, Antonio, Boumediene, Karim, Baugé, Catherine, Normandie Université (NU), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Chirurgie Maxillo-Faciale, Plastique et Reconstructrice, Chirurgie Orale et implantologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Valencia, and EACR

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

42. Inhibitors of the histone methylase EZH2, a new anti-tumoral therapy ?

Author

Baugé , Catherine, Normandie Université ( NU ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Normandie Université (NU), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)

Subjects
[SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract

International audience

Published
2013

43. Interleukin-1 in osteoarthritis

Author

Baugé, Catherine, Boumediene, K., Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Normandie Université ( NU ), Kevin V Urbano, Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), and Normandie Université (NU)

Subjects
[ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013

47. Enhanced Hyaline Cartilage Matrix Synthesis in Collagen Sponge Scaffolds by Using siRNA to Stabilize Chondrocytes Phenotype Cultured with Bone Morphogenetic Protein-2 Under Hypoxia

Author

Legendre, Florence, primary, Ollitrault, David, additional, Hervieu, Magalie, additional, Baugé, Catherine, additional, Maneix, Laure, additional, Goux, Didier, additional, Chajra, Hanane, additional, Mallein-Gerin, Frédéric, additional, Boumediene, Karim, additional, Galera, Philippe, additional, and Demoor, Magali, additional

Published
2013
Full Text
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