PDF(Pubmed)
Abstract：
Mast cells are immune cells minimally present in normal tendon tissue. The increased abundance of mast cells in tendinopathy biopsies and at the sites of tendon injury suggests an unexplored role of this cell population in overuse tendon injuries. Mast cells are particularly present in tendon biopsies from patients with more chronic symptom duration and a history of intensive mechanical loading. This study, therefore, examined the cross talk between mast cells and human tendon cells in either static or mechanically active conditions in order to explore the potential mechanistic roles of mast cells in overuse tendon injuries. A coculture of isolated human tenocytes and mast cells (HMC-1) combined with Flexcell Tension System for cyclic stretching of tenocytes was used. Additionally, human tenocytes were exposed to agonists and antagonists of substance P (SP) receptors. Mast cell degranulation was assessed by measuring β-hexosaminidase activity. Transwell and cell adhesion assays were used to evaluate mast cell migration and binding to tendon extracellular matrix components (collagen and fibronectin), respectively. Gene expressions were analyzed using real time qRT-PCR. Our results indicate that mechanical stimulation of human tenocytes leads to release of SP which, in turn, activates mast cells through the Mas-related G-protein-coupled receptor X2 (MRGPRX2). The degranulation and migration of mast cells in response to MRGPRX2 activation subsequently cause human tenocytes to increase their expression of inflammatory factors, matrix proteins and matrix metalloproteinase enzymes. These observations may be important in understanding the mechanisms by which tendons become tendinopathic in response to repetitive mechanical stimulation.
摘要：
肥大细胞是在正常肌腱组织中最低限度存在的免疫细胞。肌腱病活检和肌腱损伤部位肥大细胞的丰度增加表明，该细胞群在过度使用肌腱损伤中的作用尚未被探索。肥大细胞特别存在于具有更慢性症状持续时间和强烈机械负荷史的患者的肌腱活检中。这项研究,因此,研究了肥大细胞和人肌腱细胞在静态或机械活动条件下的串扰，以探索肥大细胞在过度使用肌腱损伤中的潜在机制作用。使用分离的人肌腱细胞和肥大细胞（HMC-1）的共培养物，与FlexcellTensionSystem结合进行肌腱细胞的循环拉伸。此外,将人肌腱细胞暴露于P物质（SP）受体的激动剂和拮抗剂。通过测量β-己糖胺酶活性来评估肥大细胞脱粒。Transwell和细胞粘附试验用于评估肥大细胞迁移和与肌腱细胞外基质成分（胶原蛋白和纤连蛋白）的结合，分别。使用实时qRT-PCR分析基因表达。我们的结果表明，人肌腱细胞的机械刺激导致SP的释放，反过来,通过Mas相关的G蛋白偶联受体X2(MRGPRX2)激活肥大细胞。响应于MRGPRX2激活的肥大细胞的脱颗粒和迁移随后导致人腱细胞增加其炎症因子的表达,基质蛋白和基质金属蛋白酶。这些观察结果对于理解肌腱响应重复机械刺激而变得肌腱病态的机制可能很重要。
