Graduate Program in Physical Therapy and Rehabilitation Science, 1-242 MEB, University of Iowa, Iowa City, Iowa 52242, USA.
Ann Rheum Dis. 2010 May;69(5):903-9. doi: 10.1136/ard.2009.117168. Epub 2009 Nov 23.
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 in 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.
类风湿关节炎是一种炎症性疾病，其特征是关节内 pH 值降低、透明质酸代谢异常以及骨和软骨破坏。酸感应离子通道（ASICs）是神经系统中的主要酸感受器，尤其在感觉神经元中，对伤害感受至关重要。ASIC3 最近在滑膜细胞中被发现，滑膜细胞是非神经元关节细胞，对炎症过程至关重要。
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 值降低的反应。
采用组织化学方法比较 ASIC3+/+和 ASIC3-/-小鼠膝关节的形态、透明质酸表达和 ASIC3 表达。分离纤维母细胞样滑膜细胞（FLS），检测其对 pH 值降低的透明质酸释放和细胞内钙离子的反应。
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，也表达了 ASIC3 mRNA 和蛋白。在 FLS 培养物中，pH 值为 5.5 时增加了 ASIC3+/+ FLS 中的透明质酸释放，但在 ASIC3-/- FLS 中则没有。在 ASIC3+/+小鼠的 FLS 中，约 50%（25/53）的细胞增加了细胞内钙离子，而只有 24%（14/59）的 ASIC3-/- FLS 出现了增加。在对 pH 值 5.5 有反应的细胞中，ASIC3-/- FLS 的细胞内钙离子增加明显少于 ASIC3+/+ FLS。
ASIC3 可能作为滑膜细胞中的 pH 感受器，对关节组织中透明质酸的表达调节很重要。
