Acid-sensing ion channel 1a-mediated calcium influx regulates apoptosis of endplate chondrocytes in intervertebral discs

Li, Xia; Wu, Fan; Xu, Rui Sheng; Hu, Wei; Jiang, Donglin; Ji, Chenfeng; Chen, Fei Hu; Yuan, Feng

doi:10.1517/14728222.2014.859248

Cited by 66 publications

(58 citation statements)

References 48 publications

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“…18,19 To Exo, respectively, Figure 2E) in the purified EVs, consistent with the character of Abs. 18,19 To Exo, respectively, Figure 2E) in the purified EVs, consistent with the character of Abs.…”

Section: Oxidative Stress Increases the Generation Of Apoptotic Bodsupporting

confidence: 79%

“…Increased oxidative stress can induce chondrocyte apoptosis. 18,19 To determine the impact of oxidative stress on the production of Abs, endplate chondrocytes were treated with, or without, H 2 O 2 for varying time periods and the secreted EVs in the cultured cells were purified. As shown in Figure 2A Exo, respectively, Figure 2E) in the purified EVs, consistent with the character of Abs.…”

Section: Oxidative Stress Increases the Generation Of Apoptotic Bodmentioning

confidence: 99%

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Apoptotic bodies from endplate chondrocytes enhance the oxidative stress‐induced mineralization by regulating PPi metabolism

Yuan

et al. 2019

J Cellular Molecular Medi

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This study aimed to investigate the role of apoptotic bodies (Abs) from the oxidative stressed endplate chondrocytes in regulating mineralization and potential mechanisms. Endplate chondrocytes were isolated from rats and treated with H2O2 to induce oxidative stress. The calcium deposition for matrix mineralization in the cells was examined by histological staining. The expression levels of calcification‐related genes in individual groups of cells were determined by quantitative real time‐PCR (qRT‐PCR). Subsequently, extracellular vesicles (EVs) were purified and characterized. The effect of treatment with H2O2 and/or Abs on the mineralization, extracellular PPi metabolism and related gene expression were determined. Oxidative stress significantly increased the mineralization and promoted the generation of main Abs from endplate chondrocytes. Abs were effectively endocytosed by endplate chondrocytes and co‐localized with collagen (COL)‐II in the cytoplasm, which enhanced the mineralization, alkaline phosphatase (ALP), osteocalcin (OCN), Runt‐related transcription factor 2 (RUNX2) and COL‐I expression in endplate chondrocytes. Furthermore, treatment either H2O2 or Abs significantly decreased PPi, but increased Pi production and treatment with both further enhancing the changes in endplate chondrocytes. Similarly, treatment either H2O2 or Abs significantly decreased the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ankylosis protein (ANK) expression and ENPP1 promoter activity, but increased the tissue‐nonspecific alkaline phosphatase (TNAP) expression and TNAP promoter activity in endplate chondrocytes. Oxidative stress promoted the generation of Abs, which might enhance the oxidative stress‐mediated mineralization in endplate chondrocytes by regulating the PPi metabolism.

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Section: Oxidative Stress Increases the Generation Of Apoptotic Bodsupporting

confidence: 79%

Section: Oxidative Stress Increases the Generation Of Apoptotic Bodmentioning

confidence: 99%

Apoptotic bodies from endplate chondrocytes enhance the oxidative stress‐induced mineralization by regulating PPi metabolism

Yuan

et al. 2019

J Cellular Molecular Medi

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“…32 It was reported that ASIC1a played an important role in the pathogenesis of diseases associated with ischaemic injury, including strokes, retinal ischaemia, etc. 32 It was reported that ASIC1a played an important role in the pathogenesis of diseases associated with ischaemic injury, including strokes, retinal ischaemia, etc.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of ASIC1a induces Ca 2+ entry and leads to intracellular Ca 2+ overload, which is a primary factor that causes cell apoptosis. 32 It was reported that ASIC1a played an important role in the pathogenesis of diseases associated with ischaemic injury, including strokes, retinal ischaemia, etc. 4,18,[33][34][35] In the present study, we found that blocking ASIC1a is protectable to renal ischaemic injury.…”

Section: Discussionmentioning

confidence: 99%

Acid‐sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis

Song

Zhang

et al. 2019

J Cellular Molecular Medi

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Acidic microenvironment is commonly observed in ischaemic tissue. In the kidney, extracellular pH dropped from 7.4 to 6.5 within 10 minutes initiation of ischaemia. Acid‐sensing ion channels (ASICs) can be activated by pH drops from 7.4 to 7.0 or lower and permeates to Ca 2+ entrance. Thus, activation of ASIC1a can mediate the intracellular Ca 2+ accumulation and play crucial roles in apoptosis of cells. However, the role of ASICs in renal ischaemic injury is unclear. The aim of the present study was to test the hypothesis that ischaemia increases renal epithelia cell apoptosis through ASIC1a‐mediated calcium entry. The results show that ASIC1a distributed in the proximal tubule with higher level in the renal tubule ischaemic injury both in vivo and in vitro. In vivo, Injection of ASIC1a inhibitor PcTx‐1 previous to ischaemia/reperfusion (I/R) operation attenuated renal ischaemic injury. In vitro, HK‐2 cells were pre‐treated with PcTx‐1 before hypoxia, the intracellular concentration of Ca 2+ , mitochondrial transmembrane potential (∆ψm) and apoptosis was measured. Blocking ASIC1a attenuated I/R induced Ca 2+ overflow, loss of ∆ψm and apoptosis in HK‐2 cells. The results revealed that ASIC1a localized in the proximal tubular and contributed to I/R induced kidney injury. Consequently, targeting the ASIC1a may prove to be a novel strategy for AKI patients.

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“…Recent studies focusing on the effect of acid on chondrocytes have revealed an important role of acid-sensing ion channels (ASICs) (57,58). ASICs are a superfamily of amiloride-sensitive cationic channels and have six subunits: ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4.…”

Section: Acidic Stressmentioning

confidence: 99%

Responses and adaptations of intervertebral disc cells to microenvironmental stress: a possible central role of autophagy in the adaptive mechanism

Jiang

Yuan

Yin

et al. 2014

Connective Tissue Research

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Intervertebral discs comprise the largest avascular cartilaginous organ in the body, and its nutrient condition can be impaired by degeneration, aging and even metabolic disease. The unique microenvironment brings special stresses to various disc cell types, including nucleus pulposus cells, notochordal cells, annulus fibrosus cells and endplate chondrocytes. These cells experience nutrient starvation, acidic stress, hypoxic stress, hyperglycemic stress, osmotic stress and mechanical stress. Understanding the detailed responses and complex adaptive mechanisms of disc cells to various stresses might provide some clues to guide therapy for disc degeneration. By reviewing the published literatures describing disc cells under different hostile microenvironments, we conclude that these cells exhibit different responses to microenvironmental stresses with different mechanisms. Moreover, the interaction and combination of these stresses create a complex environment that synergistically increase or decrease influences on disc cells, compared with the effects of a single stress. Interestingly, most of these stresses activate autophagy, a self-protective mechanism by which dysfunctional protein and organelles are degraded. It is becoming clear that autophagy facilitates the cellular adaptation to stresses and might play a central role in regulating the adaptation of disc cells under stress. Therefore, autophagy modulation might be a potential therapeutic method to treat disc degeneration.

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Acid-sensing ion channel 1a-mediated calcium influx regulates apoptosis of endplate chondrocytes in intervertebral discs

Abstract: ASIC1a activation in endplate chondrocytes may trigger Ca(2+)-dependent proteases activity and signaling, which leads to apoptosis of endplate chondrocytes in IVDs.

Cited by 66 publications

References 48 publications

Apoptotic bodies from endplate chondrocytes enhance the oxidative stress‐induced mineralization by regulating PPi metabolism

Apoptotic bodies from endplate chondrocytes enhance the oxidative stress‐induced mineralization by regulating PPi metabolism

Acid‐sensing ion channel 1a is involved in ischaemia/reperfusion induced kidney injury by increasing renal epithelia cell apoptosis

Responses and adaptations of intervertebral disc cells to microenvironmental stress: a possible central role of autophagy in the adaptive mechanism

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