Involvement of acid-sensing ion channel 1a in matrix metabolism of endplate chondrocytes under extracellular acidic conditions through NF-魏B transcriptional activity

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• 作者：Feng-Lai Yuan ; Ming-Dong Zhao ; Dong-Lin Jiang ; Cheng Jin…
• 关键词：Acid ; sensing ion channel 1a ; Extracellular pH ; Metalloproteinases ; Endplate chondrocytes
• 刊名：Cell Stress and Chaperones
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：21
• 期：1
• 页码：97-104
• 全文大小：1,330 KB
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• 作者单位：Feng-Lai Yuan (1)
  Ming-Dong Zhao (2)
  Dong-Lin Jiang (1)
  Cheng Jin (1)
  Hai-Fei Liu (3)
  Ming-Hui Xu (1)
  Wei Hu (4)
  Xia Li (1)
  
  1. Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China
  2. Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai, 201508, China
  3. Department of Internal Medicine, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, 266100, China
  4. The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China
  
• 刊物主题：Biomedicine general; Cell Biology; Biochemistry, general; Immunology; Cancer Research; Neurosciences;
• 出版者：Springer Netherlands
• ISSN：1466-1268

文摘

Acidic conditions are present in degenerated intervertebral discs and are believed to be responsible for matrix breakdown. Acid-sensing ion channel 1a (ASIC1a) is expressed in endplate chondrocytes, and its activation is associated with endplate chondrocyte apoptosis. However, the precise role of ASIC1a in regulating the matrix metabolic activity of endplate chondrocytes in response to extracellular acid remains poorly understood. Aggrecan (ACAN), type II collagen (Col2a1), and matrix metalloproteinase (MMP) expressions were determined using reverse transcription (RT)-PCR and Western blot. ASIC1a was knocked down by transfecting endplate chondrocytes with ASIC1a siRNA. MMP activity and NF-魏B transcriptional activity were measured. NF-魏B transcriptional activity was assessed by examining cytosolic phosphorylated I魏B伪 and nuclear phosphorylated p65 levels. Extracellular acidic solution (pH 6.0) resulted in a decrease in ACAN and Co12a1 expressions and an increase in MMP-1, MMP-9, and MMP-13 expressions, as well as in MMP activity; while ASIC1a siRNA blocked these effects. In addition, acid-induced increase in cytosolic levels of phosphorylated I魏B伪 and nuclear levels of phosphorylated p65 in endplate chondrocytes were inhibited by ASIC1a siRNA. ASIC1a is involved in matrix metabolism of endplate chondrocytes under extracellular acidic conditions via NF-魏B transcriptional activity. Keywords Acid-sensing ion channel 1a Extracellular pH Metalloproteinases Endplate chondrocytes