Acid-sensing ion channel 1a regulates the survival of nucleus pulposus cells in the acidic environment of degenerated intervertebral discs
Objective(s): Activation of acid-sensing ion channel 1a (ASIC1a) is responsible for tissue injury caused by acidosis in nervous systems. But its physiological and pathological roles in nucleus pulposus cells (NPCs) are unclear. The aim of this study is to investigate whether ASIC1a regulates the survival of NPCs in the acidic environment of degenerated discs. Materials and Methods: NPCs were isolated and cultured followed by immunofluorescent staining and Western-blot analysis for ASIC1a. Intracellular calcium ([Ca2+]i) was determined by Ca2+-imaging using Fura-2-AM. Cell necrosis, apoptosis, and senescence following acid exposure were determined using lactate dehydrogenase (LDH) release assay, annexin V-fluorescein isothiocyanate/propidium iodide dual-staining and cell cycle analysis, respectively, followed by Western-blot analysis for apoptosis-related proteins (Bax, Bcl-2, and caspase-3) and senescence-related proteins (p53, p21, and p16). Effects of treatment with psalmotoxin-1 (PcTX1, blocker of ASIC1a) on [Ca2+]i and cell survival were investigated. Results:ASIC1a was detected in healthy NPCs, and its expression was significantly higher in degenerated cells. When NPCs were treated with PcTX1, acid-induced increases in [Ca2+]i were significantly inhibited. PcTX1 treatment also resulted in decreased LDH release, cell apoptosis and cell cycle arrest in acid condition. Acid exposure decreased the expression of Bcl-2 and increased the expression of Bax, cleaved caspase-3 and senescence-related proteins (p53, p21, and p16), which was inhibited by PcTX1. Conclusion: The present findings suggest that further understanding of ASIC1a functionality may provide not only a novel insight into intervertebral disc biology but also a novel therapeutic target for intervertebral disc degeneration.
acid-sensing ion channel 1a regulates the survival of nucleus pulposus cells in the acidic environment of degenerated intervertebral discs
objective(s): activation of acid-sensing ion channel 1a (asic1a) is responsible for tissue injury caused by acidosis in nervous systems. but its physiological and pathological roles in nucleus pulposus cells (npcs) are unclear. the aim of this study is to investigate whether asic1a regulates the survival of npcs in the acidic environment of degenerated discs. materials and methods: npcs were is...متن کامل
Adipose-derived stem cells improve the viability of nucleus pulposus cells in degenerated intervertebral discs.
Patients with degenerative disc disease (DDD) experience serious clinical symptoms, including chronic low back pain. A series of therapies have been developed to treat DDD, including physical therapy and surgical treatment. However, the therapeutic effect of such treatments has remained insufficient. Recently, stem cell‑based therapy, in which stem cells are injected into the nucleus pulposus i...متن کامل
Acid-Sensing Ion Channel 1a Regulates Fate of Rat Nucleus Pulposus Cells in Acid Stimulus Through Endoplasmic Reticulum Stress
Acid-sensing ion channel 1a (ASIC1a) participates in human intervertebral disc degeneration (IVDD) and regulates the destiny of nucleus pulposus cells (NPCs) in acid stimulus. However, the mechanism of ASIC1a activation and its downstream pathway remain unclear. Endoplasmic reticulum (ER) stress also participates in the acid-induced apoptosis of NPCs. The main purpose of this study was to inves...متن کامل
Identification of critical genes in nucleus pulposus cells isolated from degenerated intervertebral discs using bioinformatics analysis
Intervertebral disc (IVD) degeneration is a pathological process, which may lead to lower back pain. The present study aimed to investigate the pathogenesis of IVD degeneration. GSE42611 was downloaded from Gene Expression Omnibus, including 4 nucleus pulposus samples isolated from degenerated IVDs and 4 nucleus pulposus samples separated from normal IVDs. The differentially expressed genes (DE...متن کامل
Ex Vivo Observation of Human Nucleus Pulposus Chondrocytes Isolated From Degenerated Intervertebral Discs
STUDY DESIGN We performed an ex vivo study to observe cell morphology and viability of human nucleus pulposus (NP) chondrocytes isolated from degenerated intervertebral discs (IVD). PURPOSE To better understand the biological behavior of NP chondrocytes in monolayer cultures. OVERVIEW OF LITERATURE Biological repair of IVDs by cell-based therapy has been shown to be feasible in clinical tri...متن کامل
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دوره 19 شماره 8
صفحات 812- 820
تاریخ انتشار 2016-08-01
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