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Jean-pierre Pelletier - One of the best experts on this subject based on the ideXlab platform.
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strontium ranelate reduces the progression of Experimental Dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of il 1β in the synovium
Annals of the Rheumatic Diseases, 2013Co-Authors: Jean-pierre Pelletier, Daniel Lajeunesse, Mohit Kapoor, Hassan Fahmi, Alexia Blesius, Juliette Maillet, Johanne MartelpelletierAbstract:Objective To explore the disease-modifying effect, under therapeutic conditions, of strontium ranelate (SrRan) on the progression of joint structural changes and on the major pathophysiological pathways in an Experimental osteoarthritis Dog model. Methods Dogs underwent sectioning of the anterior cruciate ligament, and 4 weeks after surgery received oral treatment of SrRan 25, 50 or 75 mg/kg per day, or placebo for 12 weeks. Methods included macroscopy, picrosirius red staining, histology, subchondral bone histomorphometry, quantitative PCR, and ELISA for CTX-II level in serum. Strontium plasma and synovial fluid levels were also measured. Results At steady state, strontium blood exposures were within the clinical therapeutic range of osteoarthritis patients and correlated with strontium concentrations in synovial fluid. SrRan treatment significantly reduced the osteoarthritis cartilage lesions at all doses tested (p≤0.05). Significantly better preservation of the collagen network was also found in SrRan-treated Dogs at 50 and 75 mg/kg per day (p=0.03). The osteoarthritis subchondral bone thickening observed in osteoarthritis-placebo Dogs was significantly reduced by SrRan at 50 mg/kg per day (p=0.02). The increased gene expression levels of MMP-1, MMP-13 and cathepsin K in osteoarthritis cartilage were all significantly reduced by SrRan at 75 mg/kg per day (p≤0.03) as were, in osteoarthritis synovium, IL-1β at 50 and 75 mg/kg per day (p=0.05) and MMP-3 at all doses tested (p≤0.02). The serum level of CTX-II was reduced (p≤0.04) by SrRan at 16 weeks in Dogs treated with 50 and 75 mg/kg per day. Conclusions This study is the first to demonstrate in vivo in an animal model that SrRan reduced the progression of osteoarthritis structural changes. The inhibition of several key proteases as well as IL-1β may have contributed to the beneficial effect of SrRan.
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Oral treatment with a Brachystemma calycinum D don plant extract reduces disease symptoms and the development of cartilage lesions in Experimental Dog osteoarthritis: inhibition of protease-activated receptor 2
Annals of the rheumatic diseases, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Frédéric Paré, Eric Troncy, Maxim Moreau, Jean-pierre PelletierAbstract:Objective The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the Experimental Dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action. Methods Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred Dogs. There were two Experimental groups (n=6–7 Dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of Dogs was performed. Results Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p Conclusions Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
Arthritis research & therapy, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:Introduction The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action.
Christelle Boileau - One of the best experts on this subject based on the ideXlab platform.
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Oral treatment with a Brachystemma calycinum D don plant extract reduces disease symptoms and the development of cartilage lesions in Experimental Dog osteoarthritis: inhibition of protease-activated receptor 2
Annals of the rheumatic diseases, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Frédéric Paré, Eric Troncy, Maxim Moreau, Jean-pierre PelletierAbstract:Objective The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the Experimental Dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action. Methods Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred Dogs. There were two Experimental groups (n=6–7 Dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of Dogs was performed. Results Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p Conclusions Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
Arthritis research & therapy, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:Introduction The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action.
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Magnetic resonance imaging can accurately assess the long-term progression of knee structural changes in Experimental Dog osteoarthritis
Annals of the rheumatic diseases, 2007Co-Authors: Christelle Boileau, Johanne Martel-pelletier, Eric Troncy, Maxim Moreau, François Abram, Jean-pierre Raynauld, Marc-andré D'anjou, Jean-pierre PelletierAbstract:Objectives: Osteoarthritis (OA) structural changes take place over decades in humans. MRI can provide precise and reliable information on the joint structure and changes over time. In this study, we investigated the reliability of quantitative MRI in assessing knee OA structural changes in the Experimental anterior cruciate ligament (ACL) Dog model of OA. Methods: OA was surgically induced by transection of the ACL of the right knee in five Dogs. High resolution three dimensional MRI using a 1.5 T magnet was performed at baseline, 4, 8 and 26 weeks post surgery. Cartilage volume/thickness, cartilage defects, trochlear osteophyte formation and subchondral bone lesion (hypersignal) were assessed on MRI images. Animals were killed 26 weeks post surgery and macroscopic evaluation was performed. Results: There was a progressive and significant increase over time in the loss of knee cartilage volume, the cartilage defect and subchondral bone hypersignal. The trochlear osteophyte size also progressed over time. The greatest cartilage loss at 26 weeks was found on the tibial plateaus and in the medial compartment. There was a highly significant correlation between total knee cartilage volume loss or defect and subchondral bone hypersignal, and also a good correlation between the macroscopic and the MRI findings. Conclusion: This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of the joint structural changes during the development of OA in the ACL Dog model. The combination of this OA model with MRI evaluation provides a promising tool for the evaluation of new disease-modifying osteoarthritis drugs (DMOADs).
Johanne Martelpelletier - One of the best experts on this subject based on the ideXlab platform.
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strontium ranelate reduces the progression of Experimental Dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of il 1β in the synovium
Annals of the Rheumatic Diseases, 2013Co-Authors: Jean-pierre Pelletier, Daniel Lajeunesse, Mohit Kapoor, Hassan Fahmi, Alexia Blesius, Juliette Maillet, Johanne MartelpelletierAbstract:Objective To explore the disease-modifying effect, under therapeutic conditions, of strontium ranelate (SrRan) on the progression of joint structural changes and on the major pathophysiological pathways in an Experimental osteoarthritis Dog model. Methods Dogs underwent sectioning of the anterior cruciate ligament, and 4 weeks after surgery received oral treatment of SrRan 25, 50 or 75 mg/kg per day, or placebo for 12 weeks. Methods included macroscopy, picrosirius red staining, histology, subchondral bone histomorphometry, quantitative PCR, and ELISA for CTX-II level in serum. Strontium plasma and synovial fluid levels were also measured. Results At steady state, strontium blood exposures were within the clinical therapeutic range of osteoarthritis patients and correlated with strontium concentrations in synovial fluid. SrRan treatment significantly reduced the osteoarthritis cartilage lesions at all doses tested (p≤0.05). Significantly better preservation of the collagen network was also found in SrRan-treated Dogs at 50 and 75 mg/kg per day (p=0.03). The osteoarthritis subchondral bone thickening observed in osteoarthritis-placebo Dogs was significantly reduced by SrRan at 50 mg/kg per day (p=0.02). The increased gene expression levels of MMP-1, MMP-13 and cathepsin K in osteoarthritis cartilage were all significantly reduced by SrRan at 75 mg/kg per day (p≤0.03) as were, in osteoarthritis synovium, IL-1β at 50 and 75 mg/kg per day (p=0.05) and MMP-3 at all doses tested (p≤0.02). The serum level of CTX-II was reduced (p≤0.04) by SrRan at 16 weeks in Dogs treated with 50 and 75 mg/kg per day. Conclusions This study is the first to demonstrate in vivo in an animal model that SrRan reduced the progression of osteoarthritis structural changes. The inhibition of several key proteases as well as IL-1β may have contributed to the beneficial effect of SrRan.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:Introduction The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action.
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the inhibition of subchondral bone resorption in the early phase of Experimental Dog osteoarthritis by licofelone is associated with a reduction in the synthesis of mmp 13 and cathepsin k
Bone, 2004Co-Authors: Jean-pierre Pelletier, Daniel Lajeunesse, Stefan Laufer, Christelle Boileau, Julie. Brunet, Martin Boily, Pascal Reboul, Johanne MartelpelletierAbstract:Objective: To evaluate the morphological changes that take place in the subchondral bone and calcified cartilage zone in the Experimental anterior cruciate ligament (ACL) Dog model of osteoarthritis (OA) and analyze concomitant changes in the level of MMP-13 and cathepsin K, as well as examine the therapeutic effects of licofelone, a lipoxygenase (LO)/cyclooxygenase (COX) inhibitor, on these morphological and biochemical changes. Methods: Experimental group 1 underwent sectioning of the ACL of the right knee with no active treatment (placebo group). Experimental groups 2 and 3 underwent sectioning of the ACL of the right knee and were administered therapeutic concentrations of licofelone (2.5 or 5.0 mg/kg/day po, respectively) for 8 weeks, beginning the day following surgery. Group 4 consisted of untreated Dogs used as normal control. Specimens of subchondral bone including the calcified cartilage were selected from lesional and non-lesional areas of OA tibial plateaus. Specimens were processed for static morphometric analysis and immunohistochemical analysis for MMP-13 and cathepsin K. Results: As indicated by a reduction in bone surface and trabecular thickness, a significant loss of subchondral bone occurred in OA Dogs. These changes were associated with an increased level of MMP-13 synthesis by bone cells and an increase in the osteoclast population that stained strongly positive for cathepsin K and MMP-13. Changes were much more pronounced in the specimens taken from the lesional areas. Treatment with licofelone decreased, in a dose-dependent manner, the OA bone morphological changes at the same time it reduced the level of MMP-13 in bone cells and the number of cathepsin K and MMP-13 positive osteoclasts. Conclusions: Increased bone loss and bone resorption is associated with the development of OA cartilage lesions. Licofelone treatment was found to prevent the morphological and biochemical changes seen in early Experimental OA effectively. These findings may help explain the mechanisms by which this drug could exert its possible effect on the development of OA.
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carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in Experimental Dog osteoarthritis
The Journal of Rheumatology, 2000Co-Authors: J P Pelletier, Dragan V Jovanovic, F C Jolicoeur, George Hilal, Daniel Lajeunesse, Julio C. Fernandes, Johanne MartelpelletierAbstract:Objective. To examine the effect of a nonsteroidal antiinflammatory drug, carprofen, on the structure and metabolism of cartilage and subchondral bone in the Experimental osteoarthritic (OA) canine model. Methods. Experimental Groups 1 and 2 received a sectioning of the anterior cruciate ligament (ACL) of the right stifle joint, and were administered carprofen (2.2 and 4.4 mg/kg/twice daily/po, respectively) for 8 weeks beginning 4 weeks postsurgery. Group 3 received ACL sectioning and no treatment. Group 4 was composed of unoperated normal Dogs. Cartilage macroscopic lesions were assessed, and their histological severity was graded. Specimens of subchondral bones were fixed, decalcified, and stained with hematoxylin/eosin. The level of metalloprotease (MMP) activity in cartilage was measured. Osteoblast cells were prepared from the subchondral bone. The level of synthesis of osteoblast biomarkers (osteocalcin, alkaline phosphatase), as well as urokinase plasminogen activator (uPA) activity and insulin-like growth factor (IGF-1) in the culture medium, was estimated. Results. Carprofen treatment decreased the width of osteophytes (p < 0.01 ), the size of cartilage lesions, and the histologic severity of cartilage lesions (p < 0.008). There was no difference in the levels of MMP activity in cartilage between OA and carprofen treated groups. In OA Dogs, the subchondral bone plate was thinner and was the site of an extensive remodeling process with numerous lacunae. Dogs treated with carprofen showed a marked decrease in the remodeling activity with normal plate thickness, and subchondral bone morphology resembling that of normal Dogs. Osteoblasts from untreated OA Dogs showed slightly higher alkaline phosphatase activities and osteocalcin release that reverted back to normal upon carprofen treatment. Moreover, uPA activity and IGF- 1 levels were increased in OA Dogs and were significantly reduced in carprofen treated Dogs. Conclusion. Under therapeutic conditions, treatment with carprofen could reduce the progression of early structural changes in Experimental OA. Carprofen treatment also delays and/or prevents the abnormal metabolism of subchondral osteoblasts in this model. The hypothesis of a possible link between the protective effect of carprofen and its effect on subchondral bone is of interest in the context of therapeutic intervention.
Johanne Martel-pelletier - One of the best experts on this subject based on the ideXlab platform.
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Oral treatment with a Brachystemma calycinum D don plant extract reduces disease symptoms and the development of cartilage lesions in Experimental Dog osteoarthritis: inhibition of protease-activated receptor 2
Annals of the rheumatic diseases, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Frédéric Paré, Eric Troncy, Maxim Moreau, Jean-pierre PelletierAbstract:Objective The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the Experimental Dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action. Methods Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred Dogs. There were two Experimental groups (n=6–7 Dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of Dogs was performed. Results Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p Conclusions Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.
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Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
Arthritis research & therapy, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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Magnetic resonance imaging can accurately assess the long-term progression of knee structural changes in Experimental Dog osteoarthritis
Annals of the rheumatic diseases, 2007Co-Authors: Christelle Boileau, Johanne Martel-pelletier, Eric Troncy, Maxim Moreau, François Abram, Jean-pierre Raynauld, Marc-andré D'anjou, Jean-pierre PelletierAbstract:Objectives: Osteoarthritis (OA) structural changes take place over decades in humans. MRI can provide precise and reliable information on the joint structure and changes over time. In this study, we investigated the reliability of quantitative MRI in assessing knee OA structural changes in the Experimental anterior cruciate ligament (ACL) Dog model of OA. Methods: OA was surgically induced by transection of the ACL of the right knee in five Dogs. High resolution three dimensional MRI using a 1.5 T magnet was performed at baseline, 4, 8 and 26 weeks post surgery. Cartilage volume/thickness, cartilage defects, trochlear osteophyte formation and subchondral bone lesion (hypersignal) were assessed on MRI images. Animals were killed 26 weeks post surgery and macroscopic evaluation was performed. Results: There was a progressive and significant increase over time in the loss of knee cartilage volume, the cartilage defect and subchondral bone hypersignal. The trochlear osteophyte size also progressed over time. The greatest cartilage loss at 26 weeks was found on the tibial plateaus and in the medial compartment. There was a highly significant correlation between total knee cartilage volume loss or defect and subchondral bone hypersignal, and also a good correlation between the macroscopic and the MRI findings. Conclusion: This study demonstrated that MRI is a useful technology to provide a non-invasive and reliable assessment of the joint structural changes during the development of OA in the ACL Dog model. The combination of this OA model with MRI evaluation provides a promising tool for the evaluation of new disease-modifying osteoarthritis drugs (DMOADs).
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Licofelone reduces progression of structural changes in a canine model of osteoarthritis under curative conditions: effect on protease expression and activity.
The Journal of rheumatology, 2006Co-Authors: Maxim Moreau, Johanne Martel-pelletier, Stefan Laufer, Christelle Boileau, Julie. Brunet, Jean-pierre PelletierAbstract:OBJECTIVE: We investigated the effectiveness of licofelone, a combined 5-lipoxygenase and cyclooxygenase inhibitor, on structural changes in the anterior cruciate ligament (ACL) Experimental Dog model of osteoarthritis (OA) under therapeutic conditions. The effect of drug treatment on the expression and activity of metalloproteases in the OA cartilage was also studied. METHODS: The cranial cruciate ligament of the right stifle joint was surgically sectioned in 14 Dogs to create OA lesions. Of these Dogs, 7 received placebo treatment and served as OA controls, while 7 were treated with licofelone 2.5 mg/kg twice daily for an 8-week period, starting 4 weeks after surgery. At necropsy, macroscopic evaluations were made of the size of osteophytes and the severity of cartilage lesions on femoral condyles and tibial plateaus. Collagenase and other metalloprotease activity levels in cartilage were measured. Levels of gene expression of matrix metalloprotease (MMP-1), MMP-13, cathepsin K, and ADAMTS-5 were quantified by RT-PCR. RESUTLS: Licofelone treatment reduced the development of osteophytes and size of cartilage lesions on the femoral condyles and on the tibial plateaus (p < 0.04). Drug treatment also significantly decreased collagenase (p < 0.02) and metalloprotease (p < 0.04) activities, as well as the levels of gene expression of MMP-1 (p < 0.01), MMP-13 (p < 0.05), cathepsin K, and ADAMTS-5 (p = 0.01). CONCLUSION: Under therapeutic conditions licofelone showed the ability to reduce the progression of structural changes in Experimental Dog OA. This beneficial effect is likely mediated through decrease in the synthesis of a number of catabolic factors, including proteolytic enzymes, involved in cartilage breakdown.
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Treatment with licofelone prevents abnormal subchondral bone cell metabolism in Experimental Dog osteoarthritis.
Annals of the rheumatic diseases, 2004Co-Authors: Daniel Lajeunesse, Julio C. Fernandes, Johanne Martel-pelletier, Stefan Laufer, J P PelletierAbstract:Objectives: To determine if treatment with licofelone, a combined 5-lipoxygenase and cyclo-oxygenase inhibitor, in vivo in Experimental Dog osteoarthritis can modify bone cell metabolism in long term in vitro subchondral osteoblast cell cultures (Ob). Methods: Group 1 received sectioning of the anterior cruciate ligament (ACL) of the right knee with no active treatment (placebo group). Groups 2 and 3 received sectioning of the ACL of the right knee, and were given licofelone (2.5 or 5.0 mg/kg daily by mouth, respectively) for eight weeks beginning the day after surgery. Primary Ob were prepared from the subchondral bone plate. Levels of phenotypic markers (alkaline phosphatase activity, osteocalcin release), and urokinase plasminogen activator (uPA) and insulin-like growth factor-1 (IGF-I) levels, were evaluated in each group. Lastly, prostaglandin E 2 (PGE 2 ) and leucotriene B 4 levels were evaluated. Results: No significant differences in alkaline phosphatase activity or osteocalcin release from Ob between the three groups, under either basal or 1,25(OH) 2 D 3 induction were seen. In contrast, treatment with licofelone reduced uPA and IGF-I levels in Ob. PGE 2 levels, which were still raised in the placebo group, were decreased sharply by licofelone. A relationship was found between licofelone treatment and either the reduction in the size of lesions on tibial plateaus or the levels of uPA, IGF-I, or PGE 2 . Conclusions: Licofelone treatment prevents and/or delays the abnormal metabolism of subchondral osteoblasts in this model. Licofelone reduced PGE 2 levels after long term Ob, suggesting that the reduction in uPA and IGF-I levels is linked, at least in part, to this reduction.
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Oral treatment with a Brachystemma calycinum D don plant extract reduces disease symptoms and the development of cartilage lesions in Experimental Dog osteoarthritis: inhibition of protease-activated receptor 2
Annals of the rheumatic diseases, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Frédéric Paré, Eric Troncy, Maxim Moreau, Jean-pierre PelletierAbstract:Objective The aims of this study were to evaluate the effect of oral treatment with a whole plant extract of Brachystemma calycinum D don (BCD) on the development of osteoarthritic lesions and symptoms in the Experimental Dog anterior cruciate ligament (ACL) transection model and to document its mechanism of action. Methods Osteoarthritis was induced by sectioning the ACL of the right knee in crossbred Dogs. There were two Experimental groups (n=6–7 Dogs/group): placebo and BCD extract (200 mg/kg per day) given orally for 8 weeks. Macroscopic and histopathological evaluation of cartilage lesions and immunohistochemical analysis of cartilage to assess levels of inducible nitric oxide synthase (iNOS), matrix metalloprotease 13 (MMP-13) and protease activated receptor 2 (PAR-2) were done. A gait analysis of Dogs was performed. Results Treatment with BCD reduced the severity (depth) (p=0.04) and histopathological score (p Conclusions Treatment with BCD extract exerts a positive effect on the prevention of cartilage lesions induced by joint instability, and improves joint function. This effect was associated with the inhibition of major catabolic and inflammatory mediators. This study is the first to demonstrate that a therapeutic intervention that can inhibit PAR-2 is associated with a disease-modifying osteoarthritis effect.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
Arthritis research & therapy, 2009Co-Authors: Christelle Boileau, Johanne Martel-pelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action. Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred Dogs. There were two treatment groups (n = 8 Dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5. The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in Dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage. This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament Dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
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protective effects of total fraction of avocado soybean unsaponifiables on the structural changes in Experimental Dog osteoarthritis inhibition of nitric oxide synthase and matrix metalloproteinase 13
Arthritis Research & Therapy, 2009Co-Authors: Christelle Boileau, Johanne Martelpelletier, J. Caron, Philippe Msika, Georges Bernard Guillou, Caroline Baudouin, Jean-pierre PelletierAbstract:Introduction The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament Dog model and, second, to explore their mode of action.
