title: Involvement of acid-sensing ion channel 1a in matrix metabolism of endplate chondrocytes under extracellular acidic conditions through NF-κB transcriptional activity.
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.
authors.affiliation: Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China.
authors.forename: Feng-Lai
authors.initials: FL
authors.lastname: Yuan
authors.affiliation: Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai, 201508, China. zhaomingdong@medmail.com.cn.
authors.forename: Ming-Dong
authors.initials: MD
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China.
authors.forename: Dong-Lin
authors.initials: DL
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Internal Medicine, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, 266100, China.
authors.forename: Hai-Fei
authors.initials: HF
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Xu
authors.affiliation: The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Orthopaedics and Central Laboratory, The Third Hospital Affiliated to Nantong University, Wuxi, Jiangsu, 214041, China. lixia.ahmu.cn@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D024043:Collagen Type II / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C508321:Acan protein, rat; D062565:Acid Sensing Ion Channels; D053674:Aggrecans; C568268:Asic1 protein, rat; C511513:COL2A1 protein, rat; D024043:Collagen Type II; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D034741:RNA, Small Interfering; D000072000:NF-KappaB Inhibitor alpha; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; C576840:MMP1 protein, rat; D020781:Matrix Metalloproteinase 1
keywords: Acid-sensing ion channel 1a; Endplate chondrocytes; Extracellular pH; Metalloproteinases