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1.
J Hazard Mater ; 423(Pt B): 127239, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34844357

RESUMO

Herein, we reported a tandem multilevel reactive electrochemical membrane (REM) system was promising for the rapid and complete removal of trace antibiotics from natural waters. Results indicate that a four-stage REM module-in-series system achieved steady over 98% removal of model antibiotic norfloxacin (NOR, 100 µg·L-1) from wastewater treatment plant final effluent and surface water with a residence time of 5.4 s, and the electric energy consumption was only around 0.007-0.011 kWh·m-3. As for the oxidation mechanism, direct electron transfer (DET) oxidation process played an important role in NOR rapid oxidation, enabling the REM system to tolerate various •OH scavenges in natural waters, including natural organic matters, Cl- and HCO3-, even at very high concentration levels. Meanwhile, •OH-mediated indirect oxidation process promotes the oxidation and mineralization of NOR. Although the DET-dominated oxidation mechanism makes the REM system cannot achieve the complete mineralization of NOR with residence times of few seconds, the antibacterial activity from NOR was completely eliminated. This REM system featured effective removal performance of trace contaminants with low energy cost and was tolerant to complex waster matrix, suggesting that it could be a powerful supplementary step for wastewater/water treatment.

2.
Adv Sci (Weinh) ; : e2103631, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825784

RESUMO

Although degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, a comprehensive single-cell resolution transcript landscape of human NP is reported. Six novel human NP cells (NPCs) populations are identified by their distinct molecular signatures. The potential functional differences among NPC subpopulations are analyzed. Predictive transcripts, transcriptional factors, and signal pathways with respect to degeneration grades are explored. It is reported that fibroNPCs is the subpopulation for end-stage degeneration. CD90+NPCs are observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). Integrin αM (CD11b) and oxidized low density lipoprotein receptor 1 (OLR1) as surface markers of NP-derived G-MDSCs are uncovered. The G-MDSCs are found to be enriched in mildly degenerated (grade II and III) NP tissues compared to severely degenerated (grade IV and V) NP tissues. Their immunosuppressive function and alleviation effects on NPCs' matrix degradation are revealed in vitro. Collectively, this study reveals the NPC-type complexity and phenotypic characteristics in NP, thereby providing new insights and clues for IVDD treatment.

3.
Oxid Med Cell Longev ; 2021: 7397516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603601

RESUMO

The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H2O2-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H2O2-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.

4.
Front Bioeng Biotechnol ; 9: 718996, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34532313

RESUMO

Symptomatic adjacent segment disease (ASD) is a common challenge after anterior cervical discectomy and fusion (ACDF). The objective of this study was to compare the biomechanical effects of a second ACDF and laminoplasty for the treatment of ASD after primary ACDF. We developed a finite element (FE) model of the C2-T1 based on computed tomography images. The FE models of revision surgeries of ACDF and laminoplasty were simulated to treat one-level and two-level ASD after primary ACDF. The range of motion (ROM) and intradiscal pressure (IDP) of the adjacent segments, and stress in the cord were analyzed to investigate the biomechanical effects of the second ACDF and laminoplasty. The results indicated that revision surgery of one-level ACDF increased the ROM and IDP at the C2-C3 segment, whereas two-level ACDF significantly increased the ROM and IDP at the C2-C3 and C7-T1 segments. Furthermore, no significant changes in the ROM and IDP of the laminoplasty models were observed. The stress in the cord of the re-laminoplasty model decreased to some extent, which was higher than that of the re-ACDF model. In conclusion, both ACDF and laminoplasty can relieve the high level of stress in the spinal cord caused by ASD after primary ACDF, whereas ACDF can achieve better decompression effect. Revision surgery of the superior ACDF or the superior and inferior ACDF after the primary ACDF increased the ROM and IDP at the adjacent segments, which may be the reason for the high incidence of recurrent ASD after second ACDF.

6.
ACS Nano ; 15(9): 14709-14724, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34476937

RESUMO

Extracellular vesicles (EVs) are potential alternatives for mesenchymal stem cells (MSCs) in the treatment of musculoskeletal degenerative diseases, including intervertebral disc degeneration (IDD). Usually, EVs are internalized and then deliver bioactive molecules that impart phenotypic changes in recipient cells. For effective utilization of EVs in the IDD therapy, understanding the mechanism of EV uptake is of vital importance. In this study, we found that EVs delivered antioxidant proteins to protect against pyroptosis of nucleus pulposus cells (NPCs). In particular, the therapeutic effect of EVs decreased in TNF-α-treated NPCs due to the impaired caveolae-mediated endocytosis pathway. Transcriptome sequencing and functional verification revealed that caveolae associated protein 2 (Cavin-2) played an important role in the uptake process of EVs. We then constructed the Cavin-2-modified engineering EVs via the gene-editing of parental MSCs. These kinds of modified EVs presented an improved uptake rate in TNF-α-treated NPCs, which effectively ameliorated the cell death of NPCs in a three-dimensional hydrogel culture model and retarded the progression of IDD in the ex vivo organ culture model. Collectively, these findings illustrate the mechanism of EV uptake in NPCs and explore the application of engineering EVs in the treatment of IDD.


Assuntos
Vesículas Extracelulares , Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Transporte Biológico , Morte Celular , Humanos , Degeneração do Disco Intervertebral/terapia
7.
Environ Res ; 204(Pt A): 111995, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492278

RESUMO

Due to the potential hazard of perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (HFPO-DA, GenX) has become a typical alternative since 2009. However, GenX has recently been reported to have equal or even greater toxicity and bioaccumulation than PFOA. Considering the suitability of alternatives, it is quite essential to study and compare the degradation degree between PFOA and GenX in water. Therefore, in the present study, a comprehensive degradation comparison between them via electrooxidation with a titanium suboxide membrane anode was conducted. The degradation rate decreased throughout for PFOA, while it first increased and then decreased for GenX when the permeate flux increased from 17.3 L to 100.3 L m-2·h-1. The different responses of PFOA and GenX to flux might be attributed to their different solubilities. In addition, the higher kobs of PFOA demonstrated that it had a better degradability than GenX by 2.4-fold in a mixed solution. The fluorinated byproduct perfluoropropanoic acid (PFPrA) was detected as a GenX intermediate, suggesting that ether bridge splitting was needed for GenX electrooxidation. This study provides a reference for assessing the degradability of GenX and PFOA and indicates that it is worth reconsidering whether GenX is a suitable alternative for PFOA from the point of view of environmental protection.

8.
Psychol Res Behav Manag ; 14: 1111-1125, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335060

RESUMO

Introduction: This study proposed a model based on Izard's theory of differential emotions to examine the effects of heritage nostalgia on perceived authenticity towards tourist satisfaction and the moderation of self-congruity in Chinese niche tourism. Methods: We examined descriptive statistics to obtain an overview of the sample by using computer program SPSS 22. Then, for evaluation, partial least squares structural equation modelling (PLS-SEM) was employed as the appropriate statistical tool, and the statistical approach was implemented using the Smart PLS 3.0 computer program. Results: The results of partial least squares structural equation modelling showed that heritage nostalgia positively affects existential and object-based authenticity. Existential and object-based authenticity positively influences tourist satisfaction. Self-congruity positively moderates the relationship between existential or object-based authenticity and heritage nostalgia. Conclusion: The linkage mechanism of tourists' psychology and behavior in heritage tourism has been explored, the internal mechanisms such as heritage nostalgia, tourists' authenticity and tourists' satisfaction have been discovered, and the internal mechanism of tourists' consistency of psychology and behavior has also been explained.

9.
Oxid Med Cell Longev ; 2021: 3843145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394825

RESUMO

Previous studies have established the pathogenic role of advanced glycation end products (AGEs) accumulation in intervertebral disc degeneration (IDD). Emerging evidence indicates that ER-phagy serves as a crucial cellular adaptive mechanism during stress conditions. This study is aimed at investigating the role of FAM134B-mediated ER-phagy in human nucleus pulposus (NP) cells upon AGEs treatment and exploring its regulatory mechanisms. We observed that AGEs treatment resulted in significantly increased apoptosis, senescence, and ROS accumulation in human NP cells; meanwhile, the enhanced apoptosis and senescence by AGEs treatment could be partially alleviated with the classic ROS scavenger NAC administration. Furthermore, we confirmed that FAM134B-mediated ER-phagy was activated under AGEs stimulation via ROS pathway. Importantly, it was also found that FAM134B overexpression could efficiently relieve intracellular ROS accumulation, apoptosis, and senescence upon AGEs treatment; conversely, FAM134B knockdown markedly resulted in opposite effects. In conclusion, our data demonstrate that FAM134B-mediated ER-phagy plays a vital role in AGEs-induced apoptosis and senescence through modulating cellular ROS accumulation, and targeting FAM134B-mediated ER-phagy could be a promising therapeutic strategy for IDD treatment.

11.
Front Cell Dev Biol ; 9: 672847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239872

RESUMO

Intervertebral disc degeneration (IDD) is the primary cause of low back pain. Stress-induced DNA damage is closely relevant to the pathogenesis of IDD; however, the underlying mechanisms remain unclear. This study investigated the role of the absent in melanoma 2 (AIM2) inflammasome as a DNA damage sensor in nucleus pulposus (NP) cells. We found that the level of AIM2 increased in degenerated discs and was correlated to the degree of IDD. Knockdown of AIM2 ameliorated H2O2-induced DNA damage and apoptosis in NP cells in vitro, and retarded the progression of IDD in vivo. Furthermore, the induction of autophagy protected against cellular DNA damage via the unconventional secretion of AIM2. We further identified the Golgi re-assembly and stacking protein 55 (GRASP55) as mediator of the transport and secretion of AIM2 via an autophagic pathway. Taken together, our researches illustrate the role and regulatory mechanism of the AIM2 inflammasome during IDD. Targeting the AIM2 inflammasome may offer a promising therapeutic strategy for patients with IDD.

12.
Exp Mol Med ; 53(7): 1124-1133, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34272472

RESUMO

Intervertebral disc degeneration (IDD) is a common and early-onset pathogenesis in the human lifespan that can increase the risk of low back pain. More clarification of the molecular mechanisms associated with the onset and progression of IDD is likely to help establish novel preventive and therapeutic strategies. Recently, mitochondria have been increasingly recognized as participants in regulating glycolytic metabolism, which has historically been regarded as the main metabolic pathway in intervertebral discs due to their avascular properties. Indeed, mitochondrial structural and functional disruption has been observed in degenerated nucleus pulposus (NP) cells and intervertebral discs. Multilevel and well-orchestrated strategies, namely, mitochondrial quality control (MQC), are involved in the maintenance of mitochondrial integrity, mitochondrial proteostasis, the mitochondrial antioxidant system, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Here, we address the key evidence and current knowledge of the role of mitochondrial function in the IDD process and consider how MQC strategies contribute to the protective and detrimental properties of mitochondria in NP cell function. The relevant potential therapeutic treatments targeting MQC for IDD intervention are also summarized. Further clarification of the functional and synergistic mechanisms among MQC mechanisms may provide useful clues for use in developing novel IDD treatments.

13.
Bioengineered ; 12(1): 4320-4330, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34308759

RESUMO

Intervertebral disc degeneration (IDD) has been well-recognized as one of the causes of vast lower back pain. The objective of the current study intends to elucidate the influence and regulatory molecular mechanisms of c-Jun on IDD. This study established an IDD model of Sprague-Dawley (SD) rats by needle puncture. An LV5-c-Jun lentiviral vector was constructed and injected into rats' intervertebral disc (IVD) tissue to increase the c-Jun expression following the establishment of modeling. The pathological changes of IVD tissue structure and collagen fibers were visualized following the processes of hematoxylin-eosin (HE) staining method and transmission electron microscopy. Real-time PCR, western blot, immunohistochemistry, and ELISA assays were performed to detect the expression levels of TGF-ß, TIMP-3, COL2A1, and inflammatory cytokines. The collagen fibers were arranged in parallel and the surface was smooth after c-Jun overexpression, whereas the collagen fibers in the control group were disorderly arranged with a rough surface. The findings indicated that c-Jun was responsible for upregulating expression levels of TGF-ß, TIMP-3, and COL2A1 in the mRNA and proteins, but simultaneously downregulating expression levels of inflammatory factors IL-1ß, IL-17, IL-6, and TNF-α. c-Jun overexpression produced a positive effect on IDD, inhibited inflammatory response in vivo, and might delay the degeneration of IVD. Thus, c-Jun may act as a novel potential agent in treating IDD.

14.
Oxid Med Cell Longev ; 2021: 5584447, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239691

RESUMO

Intervertebral disc degeneration (IDD) is the primary culprit of low back pain and renders heavy social burden worldwide. Pyroptosis is a newly discovered form of programmed cell death, which is also involved in nucleus pulposus (NP) cells during IDD progression. Moderate autophagy activity is critical for NP cell survival, but its relationship with pyroptosis remains unknown. This study is aimed at investigating the relationship between autophagy and pyroptotic cell death. The pyroptosis executor N-terminal domain of gasdermin D (GSDMD-N) and inflammation-related proteins were measured in lipopolysaccharide- (LPS-) treated human NP cells. Inhibition of autophagy by siRNA transfection and chemical drugs aggravated human NP cell pyroptosis. Importantly, we found that the autophagy-lysosome pathway and not the proteasome pathway mediated the degradation of GSDMD-N as lysosome dysfunction promoted the accumulation of cytoplasmic GSDMD-N. Besides, P62/SQSTM1 colocalized with GSDMD-N and mediated its degradation. The administration of the caspase-1 inhibitor VX-765 could reduce cell pyroptosis as confirmed in a rat disc IDD model in vivo, whereas ATG5 knockdown significantly accelerated the progression of IDD. In conclusion, our study indicated that autophagy protects against LPS-induced human NP cell pyroptosis via a P62/SQSTM1-mediated degradation mechanism and the inhibition of pyroptosis retards IDD progression in vivo. These findings deepen the understanding of IDD pathogenesis and hold implications in unraveling therapeutic targets for IDD treatment.

15.
Adv Sci (Weinh) ; 8(18): e2100964, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34258884

RESUMO

Stem cell senescence contributes to stem cell exhaustion and drives various aging-associated disorders. However, strategies to rejuvenate senescent stem cells are limited. The present study proposes an approach based on triboelectric stimulation to rejuvenate senescent bone marrow mesenchymal stromal cells (BMSCs) by fabricating a pulsed triboelectric nanogenerator (P-TENG) that can produce stable pulsed current output unaffected by the triggered frequency. The senescence phenotypes of aged BMSCs are reversed by triboelectric stimulation at 30 µA at 1.5 Hz. Triboelectric stimulation enhances the proliferation of aged BMSCs and increases their pluripotency and differentiation capacity. Additionally, mechanistic investigations reveal that pulsed triboelectric stimulation by P-TENG rejuvenates senescent BMSCs by enhancing MDM2-dependent p53 degradation, which is demonstrated by loss-of-function studies of MDM2 and p53. Overall, this study identifies a new approach for the rejuvenation of senescent BMSCs and describes a promising therapeutic intervention for many diseases associated with aged BMSCs.

16.
Biomaterials ; 274: 120850, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33984637

RESUMO

Extracellular vesicles (EVs) are extracellular nanovesicles that deliver diverse cargoes to the cell and participate in cell communication. Mesenchymal stem cell (MSCs)-derived EVs are considered a therapeutic approach in musculoskeletal degenerative diseases, including intervertebral disc degeneration. However, limited production yield and unstable quality have impeded the clinical application of EVs. In the present study, it is indicated that metformin promotes EVs release and alters the protein profile of EVs. Metformin enhances EVs production via an autophagy-related pathway, concomitantly with the phosphorylation of synaptosome-associated protein 29. More than quantity, quality of MSCs-derived EVs is influenced by metformin treatment. Proteomics analysis reveals that metformin increases the protein content of EVs involved in cell growth. It is shown that EVs derived from metformin-treated MSCs ameliorate intervertebral disc cells senescence in vitro and in vivo. Collectively, these findings demonstrate the great promise of metformin in EVs-based intervertebral disc regeneration.


Assuntos
Vesículas Extracelulares , Degeneração do Disco Intervertebral , Disco Intervertebral , Células-Tronco Mesenquimais , Metformina , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Metformina/farmacologia
17.
Sci Adv ; 7(14)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33811079

RESUMO

Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO2 structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO2 structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, interleukin-4, and interleukin-10 and released the highest amount of bone morphogenetic protein-2 among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO2 honeycomb-like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (RhoA, Rac1, and CDC42), which reinforced the polarization of macrophages through the activation of the RhoA/Rho-associated protein kinase signaling pathway.

18.
Oxid Med Cell Longev ; 2021: 6670497, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628376

RESUMO

Ferroptosis is a specialized form of regulated cell death that is charactered by iron-dependent lethal lipid peroxidation, a process associated with multiple diseases. However, its role in the pathogenesis of intervertebral disc degeneration (IVDD) is rarely investigated. This study is aimed at investigating the role of ferroptosis in oxidative stress- (OS-) induced nucleus pulposus cell (NPC) decline and the pathogenesis of IVDD and determine the underlying regulatory mechanisms. We used tert-butyl hydroperoxide (TBHP) to simulate OS conditions around human NPCs. Flow cytometry and transmission electron microscopy were used to identify ferroptosis, while iron assay kit, Perl's staining, and western blotting were performed to assay the intracellular iron levels. A ferroportin- (FPN-) lentivirus and FPN-siRNA were constructed and used to explore the relationship between FPN, intracellular iron homeostasis, and ferroptosis. Furthermore, hinokitiol, a bioactive compound known to specifically resist OS and restore FPN function, was evaluated for its therapeutic role in IVDD both in vitro and in vivo. The results indicated that intercellular iron overload plays an essential role in TBHP-induced ferroptosis of human NPCs. Mechanistically, FPN dysregulation is responsible for intercellular iron overload under OS. The increase in nuclear translocation of metal-regulatory transcription factor 1 (MTF1) restored the function of FPN, abolished the intercellular iron overload, and protected cells against ferroptosis. Additionally, hinokitiol enhanced the nuclear translocation of MTF1 by suppressing the JNK pathway and ameliorated the progression of IVDD in vivo. Taken together, our results demonstrate that ferroptosis and FPN dysfunction are involved in the NPC depletion and the pathogenesis of IVDD under OS. To the best of our knowledge, this is the first study to demonstrate the protective role of FPN in ferroptosis of NPCs, suggesting its potential used as a novel therapeutic target against IVDD.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Ferroptose , Homeostase , Degeneração do Disco Intervertebral/patologia , Ferro/metabolismo , Núcleo Pulposo/patologia , Estresse Oxidativo , Adolescente , Adulto , Idoso , Sobrevivência Celular/efeitos dos fármacos , Criança , Citoproteção/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Ferroptose/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Humanos , Espaço Intracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Monoterpenos/administração & dosagem , Monoterpenos/farmacologia , Núcleo Pulposo/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo , Tropolona/administração & dosagem , Tropolona/análogos & derivados , Tropolona/farmacologia , Adulto Jovem , terc-Butil Hidroperóxido
19.
Oxid Med Cell Longev ; 2021: 8884922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628392

RESUMO

Mechanical stimulation plays a crucial part in the development of intervertebral disc degeneration (IDD). Extracellular matrix (ECM) stiffness, which is a crucial mechanical microenvironment of the nucleus pulposus (NP) tissue, contributes to the pathogenesis of IDD. The mechanosensitive ion channel Piezo1 mediates mechanical transduction. This study purposed to investigate the function of Piezo1 in human NP cells under ECM stiffness. The expression of Piezo1 and the ECM elasticity modulus increased in degenerative NP tissues. Stiff ECM activated the Piezo1 channel and increased intracellular Ca2+ levels. Moreover, the activation of Piezo1 increased intracellular reactive oxygen species (ROS) levels and the expression of GRP78 and CHOP, which contribute to oxidative stress and endoplasmic reticulum (ER) stress. Furthermore, stiff ECM aggravated oxidative stress-induced senescence and apoptosis in human NP cells. Piezo1 inhibition alleviated oxidative stress-induced senescence and apoptosis, caused by the increase in ECM stiffness. Finally, Piezo1 silencing ameliorated IDD in an in vivo rat model and decreased the elasticity modulus of rat NP tissues. In conclusion, we identified the mechanosensitive ion channel Piezo1 in human NP cells as a mechanical transduction mediator for stiff ECM stimulation. Our results provide novel insights into the mechanism of mechanical transduction in NP cells, with potential for treating IDD.


Assuntos
Apoptose , Senescência Celular , Matriz Extracelular/metabolismo , Degeneração do Disco Intervertebral/patologia , Canais Iônicos/metabolismo , Mecanotransdução Celular , Estresse Oxidativo , Adolescente , Adulto , Idoso , Animais , Fenômenos Biomecânicos , Progressão da Doença , Estresse do Retículo Endoplasmático , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Núcleo Pulposo/patologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima , Adulto Jovem
20.
Cell Prolif ; 54(2): e12987, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33415745

RESUMO

OBJECTIVES: Inappropriate or excessive compression applied to intervertebral disc (IVD) contributes substantially to IVD degeneration. The actomyosin system plays a leading role in responding to mechanical stimuli. In the present study, we investigated the roles of myosin II isoforms in the compression stress-induced senescence of nucleus pulposus (NP) cells. MATERIAL AND METHODS: Nucleus pulposus cells were exposed to 1.0 MPa compression for 0, 12, 24 or 36 hours. Immunofluorescence and co-immunoprecipitation analysis were used to measure the interaction of myosin IIA and IIB with actin. Western blot analysis and immunofluorescence staining were used to detect nuclear expression and nuclear localization of MRTF-A. In addition, the expression levels of p-RhoA/RhoA, ROCK1/2 and p-MLC/MLC were measured in human NP cells under compression stress and in degenerative IVD tissues. RESULTS: Compression stress increased the interaction of myosin IIA and actin, while the interaction of myosin IIB and actin was reduced. The actomyosin cytoskeleton remodelling was involved in the compression stress-induced fibrotic phenotype mediated by MRTF-A nuclear translocation and inhibition of proliferation in NP cells. Furthermore, RhoA/ROCK1 pathway activation mediated compression stress-induced human NP cells senescence by regulating the interaction of myosin IIA and IIB with actin. CONCLUSIONS: We for the first time investigated the regulation of actomyosin cytoskeleton in human NP cells under compression stress. It provided new insights into the development of therapy for effectively inhibiting IVD degeneration.


Assuntos
Miosina não Muscular Tipo IIA/metabolismo , Miosina não Muscular Tipo IIB/metabolismo , Estresse Mecânico , Actinas/metabolismo , Actomiosina/metabolismo , Células Cultivadas , Senescência Celular , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Metaloproteinase 3 da Matriz/metabolismo , Miosina não Muscular Tipo IIA/antagonistas & inibidores , Miosina não Muscular Tipo IIA/genética , Miosina não Muscular Tipo IIB/antagonistas & inibidores , Miosina não Muscular Tipo IIB/genética , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transativadores/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/metabolismo
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