Abstract
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-κB transcriptional activity were measured. NF-κB transcriptional activity was assessed by examining cytosolic phosphorylated IκBα 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 IκBα 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-κB transcriptional activity.
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Acknowledgments
This work was supported by the Natural Science Foundation of China (81270011; 81472125) and the Natural Science Foundation of Jiangsu Province (Grants BK20151114) and Foundation of Traditional Chinese Medicine of Jiangsu Province (YB201578).
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Xia Li and Ming-Dong Zhao contributed equally to this work.
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Yuan, FL., Zhao, MD., Jiang, DL. et al. Involvement of acid-sensing ion channel 1a in matrix metabolism of endplate chondrocytes under extracellular acidic conditions through NF-κB transcriptional activity. Cell Stress and Chaperones 21, 97–104 (2016). https://doi.org/10.1007/s12192-015-0643-7
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DOI: https://doi.org/10.1007/s12192-015-0643-7