Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF

Lin, Hui; Zhao, Lei; Ma, Xuan; Wang, Bai-Chuan; Deng, Xueqing; Cui, Min; Chen, Songfeng; Shao, Zengwu

doi:10.1016/j.bbrc.2017.04.037

Cited by 20 publications

(19 citation statements)

References 28 publications

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“…Cells were seeded in 6-well plates (5:0 × 10 4 per well) or 96-well plates (0:5 × 10 4 per well) and cultured for 2 days before starting the experiments. As described previously [6], after pretreatment with 4-phenylbutyrate (4-PBA; Sigma, USA), dantrolene (DAN; Selleck, USA), xestospongin C (XeC; APExBIO, USA), ruthenium red (RR; Sigma, USA), or N-acetylcysteine (NAC; Sigma, USA) for 1 h, NP cells were placed in a pressure apparatus under the compression of 1 MPa. The apparatus was then sealed carefully.…”

Section: Excessive Compression Loading On Rat Np Cellsmentioning

confidence: 99%

“…. TEM was used to examine changes in the ultrastructure of the cells [6]. Briefly, cells were trypsinized, collected, and washed twice with phosphate-buffered saline (PBS).…”

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

“…Mounting evidences indicate that programmed necrosis plays a greater role in the development of IVDD than the other two programmed cell death, apoptosis and autophagic cell death [6]. The most intuitive evidence is that necrotic cells in degenerated intervertebral discs account for more than 80% of the total [7].…”

Section: Introductionmentioning

confidence: 99%

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Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca²⁺ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Lin

Peng

et al. 2021

Oxidative Medicine and Cellular Longevity

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Programmed necrosis of nucleus pulposus (NP) cells caused by excessive compression is a crucial factor in the etiopathogenesis of intervertebral disc degeneration (IVDD). The endoplasmic reticulum (ER) and mitochondria are crucial regulators of the cell death signaling pathway, and their involvement in IVDD has been reported. However, the specific role of ER stress (ERS) and ER-mitochondria interaction in compression-induced programmed necrosis of NP cells remains unknown. Our studies revealed that compression enhanced ERS and the association between ER and mitochondria in NP cells. Suppression of ERS via 4-phenylbutyrate (4-PBA) or ER-mitochondrial Ca2+ crosstalk by inhibiting the inositol 1,4,5-trisphosphate receptor, glucose-regulated protein 75, voltage-dependent anion-selective channel 1 complex (IP3R–GRP75–VDAC1 complex) protected NP cells against programmed necrosis related to the poly(ADP-ribose) polymerase (PARP) apoptosis-inducing factor (AIF) pathway. Moreover, excessive reactive oxygen species are critical activators of ERS, leading to mitochondrial Ca2+ accumulation and consequent programmed necrosis. These data indicate that ERS and ER-mitochondrial Ca2+ crosstalk may be potential therapeutic targets for the treatment of IVDD-associated disorders. These findings provide new insights into the molecular mechanisms underlying IVDD and may provide novel therapeutic targets.

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Section: Excessive Compression Loading On Rat Np Cellsmentioning

confidence: 99%

“…. TEM was used to examine changes in the ultrastructure of the cells [6]. Briefly, cells were trypsinized, collected, and washed twice with phosphate-buffered saline (PBS).…”

Section: Transmission Electron Microscopy (Tem)mentioning

confidence: 99%

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Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca²⁺ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Lin

Peng

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…N-acetylcysteine and ascorbate-2-monophosphate could protect mitochondria to improve the survival rate of transplanted MSCs by decreasing necroptosis 67 . We found that necroptosis was also involved in compression-induced NP cell death by examining compression-induced cell death (at the magnitude of 1 MPa) 54,68 . Whether necroptosis plays the analogous role in IVD stem/progenitor cells needs further investigation.…”

Section: Autophagy Apoptosis and Necroptosis Of Stem Cells Under Admentioning

confidence: 99%

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Ma¹,

Chen²,

et al. 2019

Osteoarthritis and Cartilage

106

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Intervertebral disc (IVD) degeneration is frequently associated with Low back pain (LBP), which can severely reduce the quality of human life and cause enormous economic loss. However, there is a lack of long-lasting and effective therapies for IVD degeneration at present. Recently, stem cell based tissue engineering techniques have provided novel and promising treatment for the repair of degenerative IVDs. Numerous studies showed that stem/progenitor cells exist naturally in IVDs and could migrate from their niche to the IVD to maintain the quantity of nucleus pulposus (NP) cells. Unfortunately, these endogenous repair processes cannot prevent IVD degeneration as effectively as expected. Therefore, theoretical basis for regeneration of the NP in situ can be obtained from studying the mechanisms of endogenous repair failure during IVD degeneration. Although there have been few researches to study the mechanism of cell death and migration of stem/progenitor cells in IVD so far, studies demonstrated that the major inducing factors (compression and hypoxia) of IVD degeneration could decrease the number of NP cells by regulating apoptosis, autophagy, and necroptosis, and the particular chemokines and their receptors played a vital role in the migration of mesenchymal stem cells (MSCs). These studies provide a clue for revealing the mechanisms of endogenous repair failure during IVD degeneration. This article reviewed the current research situation and progress of the mechanisms through which IVD stem/progenitor cells failed to repair IVD tissues during IVD degeneration. Such studies provide an innovative research direction for endogenous repair and a new potential treatment strategy for IVD degeneration.

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“…Protein from the culture medium as well as cell lysates in each group was collected after preparation with lysis buffer (RIPA Lysis Buffer, Beyotime, China) on ice. Lysate proteins were separated with SDS-PAGE and transferred to PVDF membranes following the routine mentioned before [ 20 ]. Primary antibodies against SOX9 (Abcam, USA), collagen type II (Novus Biologicals, USA), aggrecan (Novus Biologicals, USA), or β -actin (Tianjin Sungene Biotech Co., China) were applied to blots labeling at 4°C overnight.…”

Section: Methodsmentioning

confidence: 99%

Link Protein N-Terminal Peptide as a Potential Stimulating Factor for Stem Cell-Based Cartilage Regeneration

Wang

Cui

et al. 2018

Stem Cells International

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Background Link protein N-terminal peptide (LPP) in extracellular matrix (ECM) of cartilage could induce synthesis of proteoglycans and collagen type II in cartilaginous cells. Cartilage stem/progenitor cells (CSPCs), the endogenous stem cells in cartilage, are important in cartilage degeneration and regeneration. We hypothesized that LPP could be a stimulator for stem cell-based cartilage regeneration by affecting biological behaviors of CSPC. Methods CSPCs were isolated from rat knee cartilage. We evaluated the promoting effect of LPP on proliferation, migration, and chondrogenic differentiation of CSPCs. The chondrogenic differentiation-related genes and proteins were quantitated. Three-dimensional culture of CSPC was conducted in the presence of TGF-β3 or LPP, and the harvested pellets were analyzed to assess the function of LPP on cartilage regeneration. Results LPP stimulated the proliferation of CSPC and accelerated the site-directional migration. Higher expression of SOX9, collagen II, and aggrecan were demonstrated in CSPCs treated with LPP. The pellets treated with LPP showed more distinct characteristics of chondroid differentiation than those with TGF-β3. Conclusion LPP showed application prospect in cartilage regeneration medicine by stimulating proliferation, migration, and chondrogenic differentiation of cartilage stem/progenitor cells.

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Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF

Cited by 20 publications

References 28 publications

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca²⁺ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca²⁺ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Link Protein N-Terminal Peptide as a Potential Stimulating Factor for Stem Cell-Based Cartilage Regeneration

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Drp1 mediates compression-induced programmed necrosis of rat nucleus pulposus cells by promoting mitochondrial translocation of p53 and nuclear translocation of AIF

Cited by 20 publications

References 28 publications

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca2+ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca2+ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Link Protein N-Terminal Peptide as a Potential Stimulating Factor for Stem Cell-Based Cartilage Regeneration

Contact Info

Product

Resources

About

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca²⁺ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression

Reactive Oxygen Species Regulate Endoplasmic Reticulum Stress and ER‐Mitochondrial Ca²⁺ Crosstalk to Promote Programmed Necrosis of Rat Nucleus Pulposus Cells under Compression