Acid-sensing ion channel 3 expressed in type B synoviocytes and chondrocytes modulates hyaluronan expression and release.
Acid-sensing ion channel 3 expressed in type B synoviocytes and chondrocytes modulates hyaluronan expression and release.
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DOI：
10.1136/ard.2009.117168
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发表时间：
2010-05
影响因子：
27.4
通讯作者：
Sluka KA
中科院分区：
文献类型：
--
作者：
Kolker SJ;Walder RY;Usachev Y;Hillman J;Boyle DL;Firestein GS;Sluka KA
类风湿性关节炎是一种炎症性疾病，以关节内pH降低、透明质酸调节异常以及骨和软骨破坏为特征。酸敏感离子通道(ASICs)是神经系统，尤其是感觉神经元中的主要酸感受器，在伤害性感受中起重要作用。ASIC3是最近在滑膜细胞中发现的，滑膜细胞是炎症过程中至关重要的非神经性关节细胞。研究ASIC3在关节组织中的作用，特别是ASIC3与透明质酸的关系以及对pH降低的反应。用组织化学方法比较ASIC3+/+和ASIC3−/−小鼠膝关节的形态、透明质酸和ASIC3的表达。用分离的成纤维细胞样滑膜细胞(FLS)检测透明质酸释放和细胞内钙离子对pH降低的反应。在ASIC3+/+小鼠的组织切片中，ASIC3定位于关节软骨、生长板、半月板和B型滑膜细胞。在培养的FLS中，ASIC3mRNA和蛋白也有表达。在FLS培养中，pH 5.5可增加ASIC3+/+FLS的透明质酸释放，但不能促进ASIC3−/−FLS的释放。在ASIC3+/+小鼠的FLS中，大约50%(25/53)的细胞内钙离子升高，而只有24%(14/59)的细胞显示ASIC3−/−FLS增加。在对pH 5.5有反应的细胞中，ASIC3−/−FLS较ASIC3+/+FLS的细胞内钙升高明显减少。ASIC3可能是滑膜细胞的pH感受器，对调节关节组织中透明质酸的表达具有重要意义。
Rheumatoid arthritis is an inflammatory disease marked by intra-articular decreases in pH, aberrant hyaluronan regulation and destruction of bone and cartilage. Acid-sensing ion channels (ASICs) are the primary acid sensors in the nervous system, particularly in sensory neurons and are important in nociception. ASIC3 was recently discovered in synoviocytes, non-neuronal joint cells critical to the inflammatory process. To investigate the role of ASIC3 in joint tissue, specifically the relationship between ASIC3 and hyaluronan and the response to decreased pH. Histochemical methods were used to compare morphology, hyaluronan expression and ASIC3 expression in ASIC3+/+ and ASIC3−/− mouse knee joints. Isolated fibroblast-like synoviocytes (FLS) were used to examine hyaluronan release and intracellular calcium in response to decreases in pH. In tissue sections from ASIC3+/+ mice, ASIC3 localised to articular cartilage, growth plate, meniscus and type B synoviocytes. In cultured FLS, ASIC3 mRNA and protein was also expressed. In FLS cultures, pH 5.5 increased hyaluronan release in ASIC3+/+ FLS, but not ASIC3−/− FLS. In FLS from ASIC3+/+ mice, approximately 50% of cells (25/53) increased intracellular calcium while only 24% (14/59) showed an increase in ASIC3−/− FLS. Of the cells that responded to pH 5.5, there was significantly less intracellular calcium increases ASIC3−/− FLS compared to ASIC3+/+ FLS. ASIC3 may serve as a pH sensor in synoviocytes and be important for modulation of expression of hyaluronan within joint tissue.