Joint capsule mast cells and neuropeptides are increased within four weeks of injury and remain elevated in chronic stages of posttraumatic contractures

McCaig Centre, Bone and Joint Institute, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada.
Journal of Orthopaedic Research (Impact Factor: 2.99). 10/2009; 26(10):1313-9. DOI: 10.1002/jor.20652
Source: PubMed


The purpose of this article was to determine mast cell and neuropeptide nerve fiber numbers in joint capsules in posttraumatic contractures, as elevated numbers have been implicated in other fibrotic and contracture conditions. Twelve skeletally mature rabbits had intraarticular cortical windows removed from the medial and lateral femoral condyles and the knee joint immobilized. The contralateral unoperated limb served as a control. Equal numbers of rabbits were sacrificed 4 weeks after surgery or 40 weeks after the first surgery that included 32 weeks of remobilization. Six patients with chronic posttraumatic elbow joint contractures and six age-matched organ donor controls free of elbow contractures were also studied. Joint capsule myofibroblast, mast cell, and neuropeptide containing nerve fiber numbers were assessed with immunohistochemistry. The numbers of myofibroblasts, mast cells, and neuropeptide containing nerve fibers expressed as a percentage of total cells were significantly greater in the contracture capsules when compared to the control capsules at all time points (p < 0.0001). The range of percentages for the three components in the contracture capsules versus the controls were 41–48% versus 9–10%, 44–50% versus 11–13%, and 45–50% versus 10–12% for the acute and chronic stages of the rabbit model and the chronic stages in the human elbows, respectively. These data support the hypothesis that a myofibroblast–mast cell–neuropeptide fibrosis axis may underlie some of the pathologic changes in the joint capsule in posttraumatic contractures. Approaches designed to manipulate this axis, such as preventing degranulation of mast cells, warrant further investigation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1313–1319, 2008

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Available from: Kevin A Hildebrand, Oct 09, 2015
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    • "They then produce collagen and release extracellular matrix, which ultimately results in the formation of abundant scar tissue and adhesion. Intraarticular adhesion may cause joint stiffness, pain, cartilage degeneration and other severe functional impairments345. "
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    ABSTRACT: The aim of this study was to investigate the efficacy of topical application of colchicine in reducing intraarticular adhesion in rabbits. Thirty-six rabbits were randomly and equally divided into three groups. An approximately 10 × 10 mm(2) area of cortical bone was removed from both sides of the left femoral condyle, and the cancellous bone underneath was exposed. Cotton pads soaked with different concentrations of colchicine or saline were applied to the decorticated areas for 10 minutes. The surgical limb was fixed in a flexed position for 4 weeks postoperatively. To evaluate knee intraarticular adhesion, we performed macroscopic evaluation, histological and collagen density analyses, hydroxyproline content determination, fibroblast counting and densitometric analyses. The results showed that loose collagen tissues with little or no adhesion were present around the decorticated areas in the group treated with 0.5 mg/ml colchicine. The intraarticular adhesion score, hydroxyproline content, number of fibroblasts and densitometric value in this group were also significantly lower than those in the other groups. There was moderate intraarticular adhesion in the group treated with 0.1 mg/ml colchicine. However, dense scar tissue with dense adhesions was found in the control group. In conclusion, topical application of 0.5 mg/ml colchicine may reduce knee intraarticular adhesion.
    Scientific Reports 09/2014; 4:6405. DOI:10.1038/srep06405 · 5.58 Impact Factor
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    • "The surgical procedure is a stress factor and causes damage to the tissues, which mobilises inflammatory cells. Substance P and calcitonin-G-related peptide activate mast cells, which release mediators, increasing differentiation and proliferation of the myofibroblasts [15–17]. Transforming growth factor-β positively influences myofibroblast differentiation, while female-sex hormones and TNF-α have negative effects on them [17, 18]. "
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    ABSTRACT: Mast cells, originating from bone marrow pluripotential cells are generally populated near to strategic locations of mammalian body. They store a wide variety of biologically active molecules in their granules and also can de novo synthesize an additional spectrum of mediators, depending on their microenvironment, phenotype and status. Mast cells have numerous receptors that can trigger a wide spectrum of cellular responses, some of them which can be preprogrammed against specific pathogens. Mast cells secrete mediators, go under total degranulation, or degranulate only some of the specific granules with required content according to the environmental conditions, pathogens or signaling molecules binding to their receptors. Mast cells are functionally multi faceted cells. A single cell can behave such as an immune cell, an endocrine cell and even as a sensorial neuron. In this context, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis. Specifically the mast cells proximal to nerve fibers, contain, secrete and respond to, several neuropeptides, suggesting many potential functions for mast cells in health and disease. Mast cells are target cells for neuropeptides and, they have distinct profiles of responsiveness to these molecules. This extends the flexibility of neurogenic signaling pathways via reciprocity. Those neuropeptides have direct and indirect effects on mast cells such as inducing or suppression of degranulation, triggering, modulation or amplification of mediator content and release. The exploration of interactions of mast cells and neurons is a promising field of study which may bring treatments to several diseases. Since mast cells seem to form the major link between neurons and inflammation via neuropeptides, mast cell and mast cell mediator connection may lead to a better understanding of the autocrine, paracrine, and neuro-immuneendocrine systems in physiology and physiopathology. Therefore, mast cell manipulator drug designs, capable of granular content modulation, with effects on, selective mediator release, activity and, ablation of mast cells, would be very beneficial for the treatment of various diseases that mast cells may be involved in.
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