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

in Osteoarthritis and Cartilage (2013), 21

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See detailSirt1-deficient mice exhibit an altered cartilage phenotype.
Gabay, Odile; Zaal, Kristien J.; Sanchez, Christelle ULg et al

in Joint, bone, spine : revue du rhumatisme (2013), 80(6), 613-20

OBJECTIVE: We previously demonstrated that Sirt1 regulates apoptosis in cartilage in vitro. Here we attempt to examine in vivo cartilage homeostasis, using Sirt1 total body knockout (KO) mice. METHOD ... [more ▼]

OBJECTIVE: We previously demonstrated that Sirt1 regulates apoptosis in cartilage in vitro. Here we attempt to examine in vivo cartilage homeostasis, using Sirt1 total body knockout (KO) mice. METHOD: Articular cartilage was harvested from hind paws of 1-week and 3-week-old mice carrying wild type (WT) or null Sirt1 gene. Knees of Sirt1 haploinsufficient mice also were examined, at 6 months. Joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. RESULTS: We found that articular cartilage tissue sections from Sirt1 KO mice up to 3 weeks of age exhibited low levels of type 2 collagen, aggrecan, and glycosaminoglycan content. In contrast, protein levels of MMP-13 were elevated in the Sirt1 KO mice, leading to a potential increase of cartilage breakdown, already shown in the heterozygous mice. Additional results showed elevated chondrocyte apoptosis in Sirt1 KO mice, as compared to WT controls. In addition to these observations, PTP1b (protein tyrosine phosphatase b) was elevated in the Sirt1 KO mice, in line with previous reports. CONCLUSION: The findings from this animal model demonstrated that Sirt1 KO mice presented an altered cartilage phenotype, with an elevated apoptotic process and a potential degradative cartilage process. [less ▲]

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See detailSirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model.
Gabay, Odile; Sanchez, Christelle ULg; Dvir-Ginzberg, Mona et al

in Arthritis and Rheumatism (2013), 65(1), 159-66

OBJECTIVE: We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to ... [more ▼]

OBJECTIVE: We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to determine if SIRT-1 enzymatic activity plays a protective role in cartilage homeostasis in vivo, by investigating mice with SIRT-1 mutations to characterize their cartilage. METHODS: Articular cartilage was harvested from the paws and knees of 5- and 6-month-old wild-type (WT) mice and mice homozygous for SIRT-1(tm2.1Mcby) (SIRT-1(y/y) ), an allele carrying a point mutation that encodes a SIRT-1 protein with no enzymatic activity (y/y mice). Mice ages 2 days old and 6-7 days old were also examined. Mouse joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. RESULTS: We found that articular cartilage tissue sections from y/y mice of up to 6 months of age contained reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to their WT littermates. Consistent with these observations, protein tyrosine phosphatase 1b was elevated in the y/y mice. CONCLUSION: Our in vivo findings in this animal model demonstrate that mice with defective SIRT-1 also have defective cartilage, with elevated rates of cartilage degradation with age. Hence, normal cartilage homeostasis requires enzymatically active SIRT-1 protein. [less ▲]

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See detailIncreased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice.
Gabay, Odile; Oppenhiemer, Hanna; Meir, Hadar et al

in Annals of the Rheumatic Diseases (2012), 71(4), 613-6

OBJECTIVE: A growing body of evidence indicates that the protein deacetylase, SirT1, affects chondrocyte biology and survival. This report aims to evaluate in vivo attributes of SirT1 in cartilage biology ... [more ▼]

OBJECTIVE: A growing body of evidence indicates that the protein deacetylase, SirT1, affects chondrocyte biology and survival. This report aims to evaluate in vivo attributes of SirT1 in cartilage biology of 129/J murine strains. METHODS: Heterozygous haploinsufficient (SirT1(+/-)) and wild-type (WT; SirT1(+/+)) 129/J mice aged 1 or 9 months were systematically compared for musculoskeletal features, scored for osteoarthritis (OA) severity, and monitored for chondrocyte apoptosis in articular cartilage. Sections of femorotibial joints were stained for type II collagen and aggrecan. Protein extracts from articular chondrocytes were isolated and immunoblotted for SirT1 and active caspase 3. RESULTS: Phenotypic observations show that, at 1 month of age, SirT1(+/-) mice were smaller than WT and showed a significant decrease in full-length SirT1 (FLSirT1; 110 kDa) protein levels. Levels of FLSirT1 were further decreased in both strains at 9 months. Immunoblot assays for 9-month-old strains revealed the presence of the inactive cleaved SirT1 variant (75 SirT1; 75 kDa) in WT mice, which was undetected in age-matched SirT1(+/-) mice. Nine-month-old SirT1(+/-) mice also showed increased OA and increased levels of apoptosis compared with age-matched WT mice. CONCLUSION: The data suggest that the presence of 75 SirT1 may prolong viability of articular chondrocytes in adult (9-month-old) mice. [less ▲]

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See detailEpigenetics, sirtuins and osteoarthritis.
Gabay, Odile; Sanchez, Christelle ULg

in Joint, bone, spine : revue du rhumatisme (2012), 79(6), 570-3

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in ... [more ▼]

Epigenetics, modifications of the DNA other than changes on the DNA sequences, is frequently studied in cancer research and aging. DNA methylation, mi-RNA, and histones deacetylation are investigated in different pathologies, including inflammatory diseases and age-related diseases such as osteoarthritis (OA). In this review, we focus on the chromatin-modifying enzymes in arthritic pathologies, and more particularly on Sirtuins. We also review the role of Sirt1 in OA, which has been highlighted in recent publications, and examine the possible protective role Sirt1 could play in this disease. Moreover, we discuss the possible therapeutic target of such a protein, reviewing the potential inhibitors/activators of this enzyme and their properties. [less ▲]

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See detailRegulation of subchondral bone osteoblast metabolism by cyclic compression.
Sanchez, Christelle ULg; Pesesse, Laurence ULg; Gabay, Odile et al

in Arthritis and Rheumatism (2012), 64(4), 1193-203

OBJECTIVE: Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure ... [more ▼]

OBJECTIVE: Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure applied to the articulation was responsible for these metabolic changes. This study was undertaken to evaluate the effects of cyclic compression on osteoblasts from OA subchondral bone. METHODS: Osteoblasts were isolated from sclerotic and nonsclerotic areas of human OA subchondral bone. After 28 days, the osteoblasts were surrounded by an abundant extracellular matrix and formed a resistant membrane, which was submitted to cyclic compression (1 MPa at 1 Hz) for 4 hours. Gene expression was evaluated by reverse transcription-polymerase chain reaction. Protein production in culture supernatants was quantified by enzyme-linked immunosorbent assay or visualized by immunohistochemistry. RESULTS: Compression increased the expression of genes coding for interleukin-6 (IL-6), cyclooxygenase 2, RANKL, fibroblast growth factor 2, IL-8, matrix metalloproteinase 3 (MMP-3), MMP-9, and MMP-13 but reduced the expression of osteoprotegerin in osteoblasts in both sclerotic and nonsclerotic areas. Colalpha1(I) and MMP-2 were not significantly affected by mechanical stimuli. Nonsclerotic osteoblasts were significantly more sensitive to compression than sclerotic ones, but after compression, differences in messenger RNA levels between nonsclerotic and sclerotic osteoblasts were largely reduced or even abolished. Under basal conditions, sclerotic osteoblasts expressed similar levels of alpha5, alphav, beta1, and beta3 integrins and CD44 as nonsclerotic osteoblasts but 30% less connexin 43, an important mechanoreceptor. CONCLUSION: Genes involved in subchondral bone sclerosis are mechanosensitive. After compression, nonsclerotic and sclerotic osteoblasts expressed a similar phenotype, suggesting that compression could be responsible for the phenotype changes in OA subchondral osteoblasts. [less ▲]

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See detailSIRT1-deficient mice exhibit an altered cartilage phenotype and undergo increased cartilage breakdown and apoptosis
Gabay, Odile; Sanchez, Christelle ULg; Dvir-Ginzberg, Mona et al

Conference (2011, September)

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See detailSIRT1-deficient mice exhibit an altered cartilage phenotype
Gabay, Odile; Sanchez, Christelle ULg; Dvir-Ginzberg, Mona et al

in Arthritis and Rheumatism (2011), 63(10), 702

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See detailSIRT1-deficient mice exhibit an altered cartilage phenotype and undergo increased cartilage breakdown and apoptosis
Gabay, Odile; Sanchez, Christelle ULg; Dvir-Ginzberg, Mona et al

in Osteoarthritis and Cartilage (2011), 19(Suppl 1), 33

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See detailBio-ingénierie du cartilage
Gabay, Odile; Sanchez, Christelle ULg; Taboas, Juan

in Revue du Rhumatisme (2010), 77(4), 319-322

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See detailStigmasterol: a phytosterol with potential anti-osteoarthritic properties.
Gabay, Odile; Sanchez, Christelle ULg; Salvat, Colette et al

in Osteoarthritis and Cartilage (2010), 18(1), 106-16

OBJECTIVE: Although most studies have focused on the cholesterol-lowering activity of stigmasterol, other bioactivities have been ascribed to this plant sterol compound, one of which is a potential anti ... [more ▼]

OBJECTIVE: Although most studies have focused on the cholesterol-lowering activity of stigmasterol, other bioactivities have been ascribed to this plant sterol compound, one of which is a potential anti-inflammatory effect. To investigate the effects of stigmasterol, a plant sterol, on the inflammatory mediators and metalloproteinases produced by chondrocytes. METHOD: We used a model of newborn mouse chondrocytes and human osteoarthritis (OA) chondrocytes in primary culture stimulated with or without IL-1beta (10 ng/ml), for 18 h. Cells were pre-incubated for 48 h with stigmasterol (20 microg/ml) compared to untreated cells. We initially investigated the presence of stigmasterol in chondrocyte, compared to other phytosterols. We then assessed the role of stigmasterol on the expression of various genes involved in inflammation (IL-6) and cartilage turn-over (MMP-3, -13, ADAMTS-4, -5, type II collagen, aggrecan) by quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Additional experiments were carried out to monitor the production of MMP-3 and prostaglandin E2 (PGE(2)) by specific immuno-enzymatic assays. We eventually looked at the role of stigmasterol on NF-kappaB activation by western blot, using an anti-IkappaBalpha antibody. RESULTS: After 18 h of IL-1beta treatment, MMP-3, MMP-13, ADAMTS-4, but not ADAMTS-5 RNA expression were elevated, as well as MMP-3 and PGE(2) protein levels in mouse and human chondrocytes. Type II collagen and aggrecan mRNA levels were significatively reduced. Pre-incubation of stigmasterol to IL-1beta-treated cells significantly decreased these effects described above (significant reduction of MMP-3 mRNA in human and mouse, MMP-3 protein in mouse, MMP-13 mRNA in mouse and human, ADAMTS-4 mRNA in human, PGE(2) protein in human and mouse) Finally, stigmasterol was capable of counteracting the IL-1beta-induced NF-kappaB pathway. CONCLUSION: This study shows that stigmasterol inhibits several pro-inflammatory and matrix degradation mediators typically involved in OA-induced cartilage degradation, at least in part through the inhibition of the NF-kappaB pathway. These promising results justify further ex vivo and in vivo investigations with stigmasterol. [less ▲]

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See detailUpdate in cartilage bio-engineering.
Gabay, Odile; Sanchez, Christelle ULg; Taboas, Juan M

in Joint Bone Spine (2010), 77(4), 283-6

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See detailEffects of compression on human subchondral osteoblast metabolism
Kesteloot, Frédéric ULg; Gabay, Odile; Msika, Philippe et al

Poster (2009, May 24)

Introduction. Recent data showed that subchondral bone plays an important role in osteoarthritis (OA). Metabolic and morphologic modifications in this tissue contribute to the degradation of the ... [more ▼]

Introduction. Recent data showed that subchondral bone plays an important role in osteoarthritis (OA). Metabolic and morphologic modifications in this tissue contribute to the degradation of the overlaying cartilage. It was suggested that abnormal mechanical pressure exerted onto the articulation was responsible to these changes. Here, we evaluated the effects of compression on osteoblasts from subchondral bone. Method. Osteoblasts were isolated from sclerotic (SC) or non-sclerotic (NSC) areas of human OA subchondral bone. After 28 days, osteoblasts were surrounded by their matrix. This osteoblasts-containing membrane was then placed onto a Biopress Flexercell plate and submitted to a 4h 1.67 MPa compression (1 Hz). Expression of IL-6, IL-8, COX-2, VEGF, IGF-1, OPG and RANKL was evaluated by RT-PCR. IL-6, IL-8 and PGE2 were quantified by ELISA. Results. Basal IL-6, VEGF, COX-2, IGF-1 and RANKL mRNA levels were significantly increased in SC osteoblasts as compared to NSC. By contrast, SC osteoblasts expressed less OPG than those from NSC areas. Compressions induced the expression of genes coding for IL-6, IL-8, COX-2, IGF-1, VEGF and RANKL but decreased the expression of OPG in NSC osteoblasts (p<0.01). Interestingly, compressed NSC osteoblasts expressed similar levels of these genes than SC osteoblasts. Conclusions. We show that our model of compression can induce in NSC osteoblasts a phenotype similar to this observed in sclerotic areas. Moreover, SC osteoblasts are less sensitive to mechanical stimuli than NSC osteoblasts. These results clarify the role of compression in the pathogenesis of subchondral bone sclerosis and allow new perspectives of research in this field. [less ▲]

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See detailCompression induces the expression of a sclerotic phenotype in human subchondral osteoblasts
Sanchez, Christelle ULg; Gabay, Odile; Pesesse, Laurence ULg et al

in Osteoarthritis and Cartilage (2009), 17(suppl 1), 95

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See detailMechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts.
Sanchez, Christelle ULg; Gabay, Odile; Salvat, Colette et al

in Osteoarthritis and Cartilage (2009), 17(4), 473-81

OBJECTIVES: In osteoarthritis (OA), mechanical factors play a key role, not only in cartilage degradation, but also in subchondral bone sclerosis. The aim of this study was to develop on original ... [more ▼]

OBJECTIVES: In osteoarthritis (OA), mechanical factors play a key role, not only in cartilage degradation, but also in subchondral bone sclerosis. The aim of this study was to develop on original compression model for studying the effect of mechanical stress on osteoblasts. MATERIALS AND METHODS: We investigate the effects of compression on primary calvaria osteoblasts isolated from newborn mice and cultured for 28 days in monolayer. At the end of this period, osteoblasts were embedded in a newly synthesized extracellular matrix which formed a three-dimensional membrane. This membrane was then submitted to compression in Biopress Flexercell plates (1-1.7 MPa compressions at 1 Hz frequency) during 1-8h. The expression of 20 genes was investigated by real time reverse transcriptase polymerase chain reaction. Interleukin (IL)-6, matrix metalloproteinase (MMP)-3 and prostaglandin (PG)E(2) were assayed in the culture medium by specific immunoassays. RESULTS: The compression highly increased IL-6 and cyclooxygenase (COX)-2 mRNA levels in osteoblasts. In parallel, increased amount of IL-6 and PGE(2) was found in the supernatant of loaded osteoblasts. This stimulation reached a maximum after 4h of 10% compression. MMP-2, MMP-3, and MMP-13 mRNA levels were also increased by compressive stress, while 15-hydroxyprostaglandin-dehydrogenase and osteoprotegerin (OPG) start to decrease at hour 4. COX-1, microsomial PG E synthase-1 (mPGES1), mPGES2 and cytosolic PGES and receptor activator of nuclear factor ligand (RANKL) were unmodified. Finally, we observed that alpha 5 beta 1 integrin, intracellular Ca(++), nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 pathways were involved in the compression-induced IL-6 and PGE(2) production. IL-6 neutralizing antibodies and piroxicam inhibited the decrease OPG expression, but did not modify RANKL mRNA level, indicating that IL-6 and PGE(2) induce a decrease of the OPG/RANKL ratio. CONCLUSION: This work demonstrates that IL-6 is mechano-sensitive cytokine and probably a key factor in the biomechanical control of bone remodeling in OA. [less ▲]

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See detailArthrose et obésité : Modèles expérimentaux
Gabay, Odile; Hall, David; Berenbaum, Francis et al

in Revue du Rhumatisme (2008), 75(12), 1215-1219

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See detailAnti-inflammatory properties of stigmasterol in cartilage: new insights
Gabay, Odile; Sanchez, Christelle ULg; Chevy, F. et al

Poster (2008)

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See detailEtude des effets de la compression sur le métabolisme des ostéoblastes sous-chondraux humains
Sanchez, Christelle ULg; Mathy, Marianne ULg; Gabay, Odile et al

in Revue du Rhumatisme (2008), 75(10-11), 1021

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