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David A. Hart - One of the best experts on this subject based on the ideXlab platform.
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KETOTIFEN INHIBITS FIBROBLAST CONTRACTILE RESPONSES IN THE PRESENCE OF Mast CellS
2018Co-Authors: Kevin A. Hildebrand, Paul T. Salo, David A. Hart, Mei Zhang, D. BefusAbstract:SummaryPrevious work in a rabbit model of post-traumatic joint contractures shows that the Mast Cell Stabilizer ketotifen decreases contracture severity. We show here that ketotifen decreases collagen gel contraction mediated by rabbit joint capsule fibroblasts when Mast Cells are present.IntroductionKetotifen was shown to decrease contracture severity and associated joint capsule fibrosis in an animal model of post-traumatic joint contractures. Ketotifen prevents the release of profibrotic growth factors from Mast Cells (MC). An in vitro collagen gel contraction assay is used to examine the effect of ketotifen on joint capsule fibroblasts obtained from this animal model.MethodsSix New Zealand White rabbits had a standardised procedure to induce post-traumatic joint contractures and the joint capsule was harvested 4 weeks later. The capsules were minced, placed into T75 culture flasks and incubated at 370C in a humidified atmosphere containing 5% CO2. The Joint Capsule fibroblasts (JC, 2.5 × 105 Cells/mL)...
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A myofibroblast–Mast Cell–neuropeptide axis of fibrosis in post‐traumatic joint contractures: An in vitro analysis of mechanistic components
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2014Co-Authors: Kevin A. Hildebrand, A. Dean Befus, Paul T. Salo, Mei Zhang, David A. HartAbstract:Previous studies have implicated a myofibroblast-Mast Cell-neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule Cells (JC) from human elbows with post-traumatic contractures and their interactions with Mast Cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the Mast Cell Stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the Mast Cell Stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast-Mast Cell-neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions.
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A myofibroblast–Mast Cell–neuropeptide axis of fibrosis in post‐traumatic joint contractures: An in vitro analysis of mechanistic components
Journal of Orthopaedic Research, 2014Co-Authors: Kevin A. Hildebrand, A. Dean Befus, Paul T. Salo, Mei Zhang, David A. HartAbstract:Previous studies have implicated a myofibroblast–Mast Cell–neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule Cells (JC) from human elbows with post-traumatic contractures and their interactions with Mast Cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the Mast Cell Stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the Mast Cell Stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast–Mast Cell–neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1290–1296, 2014.
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The Mast Cell Stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
Inflammation Research, 2012Co-Authors: Michael J. Monument, A. Dean Befus, Paul T. Salo, David A. Hart, Mei Zhang, Kevin A. HildebrandAbstract:Objectives Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a Mast Cell Stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis. Methods Surgical joint injury was used to create stable post-traumatic contractures of the knee in skeletally mature New Zealand white rabbits. Four groups of animals were studied: a non-operated control group ( n = 8), an operated contracture group ( n = 13) and two operated groups treated with the Mast Cell Stabilizer, ketotifen, at doses of 0.5 mg/kg ( n = 9) and 1.0 mg/kg ( n = 9) twice daily. Joint capsule fibrosis was assessed by quantifying the mRNA and protein levels of α-SMA, tryptase, TGF-β1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance. Results The protein and mRNA levels of α-SMA, TGF-β1, tryptase and collagen I and III were significantly elevated in the operated contracture group compared to control ( p
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The Mast Cell Stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
Inflammation Research, 2011Co-Authors: Michael J. Monument, A. Dean Befus, Paul T. Salo, David A. Hart, Mei Zhang, Kevin A. HildebrandAbstract:Objectives Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a Mast Cell Stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis.
Kevin A. Hildebrand - One of the best experts on this subject based on the ideXlab platform.
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KETOTIFEN INHIBITS FIBROBLAST CONTRACTILE RESPONSES IN THE PRESENCE OF Mast CellS
2018Co-Authors: Kevin A. Hildebrand, Paul T. Salo, David A. Hart, Mei Zhang, D. BefusAbstract:SummaryPrevious work in a rabbit model of post-traumatic joint contractures shows that the Mast Cell Stabilizer ketotifen decreases contracture severity. We show here that ketotifen decreases collagen gel contraction mediated by rabbit joint capsule fibroblasts when Mast Cells are present.IntroductionKetotifen was shown to decrease contracture severity and associated joint capsule fibrosis in an animal model of post-traumatic joint contractures. Ketotifen prevents the release of profibrotic growth factors from Mast Cells (MC). An in vitro collagen gel contraction assay is used to examine the effect of ketotifen on joint capsule fibroblasts obtained from this animal model.MethodsSix New Zealand White rabbits had a standardised procedure to induce post-traumatic joint contractures and the joint capsule was harvested 4 weeks later. The capsules were minced, placed into T75 culture flasks and incubated at 370C in a humidified atmosphere containing 5% CO2. The Joint Capsule fibroblasts (JC, 2.5 × 105 Cells/mL)...
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A myofibroblast–Mast Cell–neuropeptide axis of fibrosis in post‐traumatic joint contractures: An in vitro analysis of mechanistic components
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2014Co-Authors: Kevin A. Hildebrand, A. Dean Befus, Paul T. Salo, Mei Zhang, David A. HartAbstract:Previous studies have implicated a myofibroblast-Mast Cell-neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule Cells (JC) from human elbows with post-traumatic contractures and their interactions with Mast Cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the Mast Cell Stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the Mast Cell Stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast-Mast Cell-neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions.
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A myofibroblast–Mast Cell–neuropeptide axis of fibrosis in post‐traumatic joint contractures: An in vitro analysis of mechanistic components
Journal of Orthopaedic Research, 2014Co-Authors: Kevin A. Hildebrand, A. Dean Befus, Paul T. Salo, Mei Zhang, David A. HartAbstract:Previous studies have implicated a myofibroblast–Mast Cell–neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule Cells (JC) from human elbows with post-traumatic contractures and their interactions with Mast Cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the Mast Cell Stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the Mast Cell Stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast–Mast Cell–neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1290–1296, 2014.
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The Mast Cell Stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
Inflammation Research, 2012Co-Authors: Michael J. Monument, A. Dean Befus, Paul T. Salo, David A. Hart, Mei Zhang, Kevin A. HildebrandAbstract:Objectives Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a Mast Cell Stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis. Methods Surgical joint injury was used to create stable post-traumatic contractures of the knee in skeletally mature New Zealand white rabbits. Four groups of animals were studied: a non-operated control group ( n = 8), an operated contracture group ( n = 13) and two operated groups treated with the Mast Cell Stabilizer, ketotifen, at doses of 0.5 mg/kg ( n = 9) and 1.0 mg/kg ( n = 9) twice daily. Joint capsule fibrosis was assessed by quantifying the mRNA and protein levels of α-SMA, tryptase, TGF-β1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance. Results The protein and mRNA levels of α-SMA, TGF-β1, tryptase and collagen I and III were significantly elevated in the operated contracture group compared to control ( p
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The Mast Cell Stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
Inflammation Research, 2011Co-Authors: Michael J. Monument, A. Dean Befus, Paul T. Salo, David A. Hart, Mei Zhang, Kevin A. HildebrandAbstract:Objectives Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a Mast Cell Stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis.
Juan-ramon Malagelada - One of the best experts on this subject based on the ideXlab platform.
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Modulatory Effect of Nitric Oxide on Mast Cells During Induction of Dextran Sulfate Sodium Colitis
Digestive Diseases and Sciences, 2007Co-Authors: Sebastian Videla, Jaime Vilaseca, Carlos Medina, Marisabel Mourelle, Francisco Guarner, Aantonio Salas, Juan-ramon MalageladaAbstract:Nitric oxide (NO) is implicated in the pathophysiology of intestinal inflammation. Intestinal Mast Cells may amplify inflammatory response and mucosal injury in inflammatory bowel disease. Our aim was to examine the role of NO and intestinal Mast Cells by investigating the effects of NO synthase (NOS) inhibitors and a Mast Cell Stabilizer during induction of dextran sulfate sodium (DSS) colitis. Colitis was induced by 4% DSS in drinking water, in rats pretreated with L-NAME or aminoguanidine. In another set of experiments, we investigated the effect of ketotifen in this setting. Inhibition of NO by L-NAME worsened DSS-induced inflammation, however, aminoguanidine had no effect. On the other hand, ketotifen abolished the deleterious effects of L-NAME on colonic inflammation, suggesting that hyperactivation of Mast Cells by NOS inhibition amplifies mucosal injury induced by DSS. Our results suggest that constitutive isoforms of NOS prevent Mast Cell activation.
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Modulatory Effect of Nitric Oxide on Mast Cells During Induction of Dextran Sulfate Sodium Colitis
Digestive Diseases and Sciences, 2007Co-Authors: Sebastian Videla, Jaime Vilaseca, Carlos Medina, Marisabel Mourelle, Francisco Guarner, Aantonio Salas, Juan-ramon MalageladaAbstract:Nitric oxide (NO) is implicated in the pathophysiology of intestinal inflammation. Intestinal Mast Cells may amplify inflammatory response and mucosal injury in inflammatory bowel disease. Our aim was to examine the role of NO and intestinal Mast Cells by investigating the effects of NO synthase (NOS) inhibitors and a Mast Cell Stabilizer during induction of dextran sulfate sodium (DSS) colitis. Colitis was induced by 4% DSS in drinking water, in rats pretreated with L-NAME or aminoguanidine. In another set of experiments, we investigated the effect of ketotifen in this setting. Inhibition of NO by L-NAME worsened DSS-induced inflammation, however, aminoguanidine had no effect. On the other hand, ketotifen abolished the deleterious effects of L-NAME on colonic inflammation, suggesting that hyperactivation of Mast Cells by NOS inhibition amplifies mucosal injury induced by DSS. Our results suggest that constitutive isoforms of NOS prevent Mast Cell activation.
Daniel Rachmilewitz - One of the best experts on this subject based on the ideXlab platform.
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Effect of Colchicine and Bisacodyl on Rat Intestinal Transit and Nitric Oxide Synthase Activity
Scandinavian journal of gastroenterology, 1997Co-Authors: Fanny Karmeli, R. Stalnikowicz, Daniel RachmilewitzAbstract:Background: Bisacodyl and colchicine affect smooth-muscle contractility, intestinal water, and electrolyte transport. Nitric oxide (NO) stimulates intestinal electrolyte secretion and has an important role as a mediator of intestinal motility. We therefore studied, in rats, the effects of these agents on nitric oxide synthase (NOS) activity and gastrointestinal transit. Methods: Rats were treated with bisacodyl (10 mg/kg intragastrically) or colchicine (5 mg/kg intraperitoneally) with or without pretreatment with ketotifen (1 mg/kg intragastrically). Rats were killed after 1, 2, and 4h. The intestine was isolated and rinsed, the mucosa scraped, and NOS activity determined. In all rats small-intestinal transit was measured 15 min after intragastric administration of charcoal. Results: Bisacodyl (10 mg/kg) and colchicine (5 mg/kg) induced a significant decrease in jejunal NOS activity. Pretreatment with the Mast Cell Stabilizer ketotifen, which has been shown to attenuate the increased permeability induced ...
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Effect of Drugs on Colonic Eicosanoid Accumulation in Active Ulcerative Colitis
Scandinavian Journal of Gastroenterology, 1992Co-Authors: Rami Eliakim, Elimelech Okon, Michael Chorev, Fanny Karmeli, Daniel RachmilewitzAbstract:The effect of immunosuppressive drugs, 4-aminosalicylic acid (4-ASA), acetyl 5-aminosalicylic acid (S-ASA), and ketotifen on human colonic eicosanoid accumulation was evaluated in view of enhanced accumulation in patients with active ulcerative colitis. Azathioprine (100 ug/ml), cyclosporin (100 ug/ml), and methotrexate (100 ug/ml) significantly inhibited, by 25–35%, prostaglandin E, (PGE,) accumulation by organ-cultured colonic mucosa of ulcerative colitis patients. Methotrexate was the only immunosuppressive drug that inhibited leukotriene B4 (LTB4) accumulation (50%), whereas azathioprine inhibited the accumulation of leukotriene C4 (LTC,) (25%). 5-ASA and its metabolite, acetyl 5-ASA, inhibited by 20–70% PGE2, LTB, and LTC4 accumulation in the culture, supporting the contention that acetyl 5-ASA is as active as 5-ASA in these respects. 4-ASA had no effect on any of the eicosanoids. Ketotifen, a Mast Cell Stabilizer, significantly inhibited the accumulation of PGE2, LTB4, and LTC4 by 33–60%. These resu...
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Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a Mast Cell Stabilizer.
Gastroenterology, 1991Co-Authors: Fanny Karmeli, Elimelech Okon, Rami Eliakim, Daniel RachmilewitzAbstract:To elucidate the possible role of substance P in the pathogenesis of acute gastric mucosal damage, rats were treated intragastrically with 1.0 mL 96% ethanol, 0.6N HCl, or 25% NaCI, with or without IP coadministration of substance P, senktide, or septide (1 μmol/L per 100 g). All three peptides were found to double the mean lesion area when compared with that induced by ethanol, whereas substance P antagonist (1 μmol/L per 100 g) prevented the expansion of damage extent. The increased damage was associated with increased gastric mucosal levels of platelet activating factor, leukotriene B4, and leukotriene C4. Substance P antagonists also reduced by half the extent of the gastric damage induced by ethanol when administered by itself. WEB 2086 (platelet-activating factor antagonist; Boehringer Ingelheim KG, Germany), hydroxyzine (H1 blocker), and Cimetidine (H2 blocker) reduced lesion area by 50%, but only in rats treated with both substance P and ethanol. Ketotifen (Mast-Cell Stabilizer) (100 μg/lOO g), administered orally 30 minutes before damage induction, totally abolished the extent of the damage induced by either ethanol or the coadministration of ethanol and peptides in the surface epithelium of the entire mucosa. The protective effect of ketotifen was accompanied by significant reduction in mucosal generation of platelet-activating factor, leukotriene C4, and leukotriene B4. Similar mucosal protection was afforded by ketotifen against damage induced by 0.6N HCl, 25% NaCl, or indomethacin. Therefore, it is suggested that substance P is involved in the pathogenesis of acute ethanol-induced gastric mucosal damage. The effective mucosal protection provided by ketotifen indicates the important role of Mast Cells and their mediators in the pathogenesis of acute gastric mucosal damage and may have therapeutic implications.
Paul T. Salo - One of the best experts on this subject based on the ideXlab platform.
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KETOTIFEN INHIBITS FIBROBLAST CONTRACTILE RESPONSES IN THE PRESENCE OF Mast CellS
2018Co-Authors: Kevin A. Hildebrand, Paul T. Salo, David A. Hart, Mei Zhang, D. BefusAbstract:SummaryPrevious work in a rabbit model of post-traumatic joint contractures shows that the Mast Cell Stabilizer ketotifen decreases contracture severity. We show here that ketotifen decreases collagen gel contraction mediated by rabbit joint capsule fibroblasts when Mast Cells are present.IntroductionKetotifen was shown to decrease contracture severity and associated joint capsule fibrosis in an animal model of post-traumatic joint contractures. Ketotifen prevents the release of profibrotic growth factors from Mast Cells (MC). An in vitro collagen gel contraction assay is used to examine the effect of ketotifen on joint capsule fibroblasts obtained from this animal model.MethodsSix New Zealand White rabbits had a standardised procedure to induce post-traumatic joint contractures and the joint capsule was harvested 4 weeks later. The capsules were minced, placed into T75 culture flasks and incubated at 370C in a humidified atmosphere containing 5% CO2. The Joint Capsule fibroblasts (JC, 2.5 × 105 Cells/mL)...
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A myofibroblast–Mast Cell–neuropeptide axis of fibrosis in post‐traumatic joint contractures: An in vitro analysis of mechanistic components
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2014Co-Authors: Kevin A. Hildebrand, A. Dean Befus, Paul T. Salo, Mei Zhang, David A. HartAbstract:Previous studies have implicated a myofibroblast-Mast Cell-neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule Cells (JC) from human elbows with post-traumatic contractures and their interactions with Mast Cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the Mast Cell Stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the Mast Cell Stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast-Mast Cell-neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions.
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A myofibroblast–Mast Cell–neuropeptide axis of fibrosis in post‐traumatic joint contractures: An in vitro analysis of mechanistic components
Journal of Orthopaedic Research, 2014Co-Authors: Kevin A. Hildebrand, A. Dean Befus, Paul T. Salo, Mei Zhang, David A. HartAbstract:Previous studies have implicated a myofibroblast–Mast Cell–neuropeptide axis of fibrosis in pathologic joint capsules from post-traumatic contractures. The hypothesis to be tested is that joint capsule Cells (JC) from human elbows with post-traumatic contractures and their interactions with Mast Cells (MC) and neuropeptides in the microenvironment underlie the pathogenesis of contractures. The hypothesis was tested using an in vitro collagen gel contraction model. The JC were isolated from human elbow capsules and mixed with neutralized PureCol collagen I. The gels were treated in various ways, including addition of MC (HMC-1), the neuropeptide substance P (SP), an NK1 receptor (SP receptor) antagonist RP67580 and the Mast Cell Stabilizer ketotifen fumarate (KF). The collagen gels were released from the wells and gel size (contraction) was measured optically at multiple time points. The JC contracted collagen gels in a dose-dependent manner. This was enhanced in the presence of MC and increased further with SP. Increasing concentrations of the SP receptor antagonist, RP67580 or the Mast Cell Stabilizer, KF decreased the magnitude of contraction. These observations identify putative mechanistic components of a myofibroblast–Mast Cell–neuropeptide axis of fibrosis in the joint capsules in post-traumatic contractures and potential prophylactic or therapeutic interventions. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1290–1296, 2014.
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The Mast Cell Stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
Inflammation Research, 2012Co-Authors: Michael J. Monument, A. Dean Befus, Paul T. Salo, David A. Hart, Mei Zhang, Kevin A. HildebrandAbstract:Objectives Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a Mast Cell Stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis. Methods Surgical joint injury was used to create stable post-traumatic contractures of the knee in skeletally mature New Zealand white rabbits. Four groups of animals were studied: a non-operated control group ( n = 8), an operated contracture group ( n = 13) and two operated groups treated with the Mast Cell Stabilizer, ketotifen, at doses of 0.5 mg/kg ( n = 9) and 1.0 mg/kg ( n = 9) twice daily. Joint capsule fibrosis was assessed by quantifying the mRNA and protein levels of α-SMA, tryptase, TGF-β1, collagen I and collagen III. Significance was tested using an ANOVA analysis of variance. Results The protein and mRNA levels of α-SMA, TGF-β1, tryptase and collagen I and III were significantly elevated in the operated contracture group compared to control ( p
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The Mast Cell Stabilizer ketotifen reduces joint capsule fibrosis in a rabbit model of post-traumatic joint contractures
Inflammation Research, 2011Co-Authors: Michael J. Monument, A. Dean Befus, Paul T. Salo, David A. Hart, Mei Zhang, Kevin A. HildebrandAbstract:Objectives Using a rabbit model of post-traumatic joint contractures, we investigated whether treatment with a Mast Cell Stabilizer after joint injury would lessen the molecular manifestations of joint capsule fibrosis.