Effects of Dynamic Loading on Cell Viability in Intervertebral Disc

2012 ◽  
Author(s):  
Qiaoqiao Zhu ◽  
Weiyong Gu
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Cell Viability ◽  
Cell Density ◽  
Cell Metabolism ◽  
Experimental Studies ◽  
Nutrient Supply ◽  
Nutrient Deprivation ◽  
Physical And Chemical

Sufficient nutrient supply has long been regarded as a crucial factor for maintaining intervertebral disc (IVD) cell viability and preventing IVD degeneration1,2. Due to avascular nature of the tissue, nutrients for IVD cells are transported, mainly by diffusion, through the dense extracellular matrix of the tissue from the peripheral and endplate vasculatures. Experimental studies on the effects of nutrient deprivation on IVD cell viability showed that glucose is the most critical nutrient affecting the cell density in IVD3–5. Because of the difficulties in studying mechano-biology of human IVD in vivo, numerical simulations are necessary to investigate how the disturbances of biological, physical, and chemical signals can affect the cellular metabolism and viability in IVD. However, to date, there is no adequate theoretical model that is able to describe the change of cell density in IVD under dynamic conditions. Therefore, the objective of this study was to develop a new constitutive model for cell growth/death in human IVD and to analyze the cell metabolism and cell viability in IVD under dynamic, mechanical loading conditions using numerical methods based on the mechano-electrochemical mixture theory6,7.

scholarly journals AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoling Liu ◽  
Chenyu Wang ◽  
Qing Yang ◽  
Yue Yuan ◽  
Yunjian Sheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Biological Function ◽  
Cell Metabolism ◽  
Hub Genes ◽  
Invasion And Migration ◽  
And Migration

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

scholarly journals MiR-144-3p Aggravated Cartilage Injury in Rheumatoid Arthritis by Regulating BMP2/PI3K/Akt Axis

2021 ◽  
Author(s):  
Mei-Li Mo ◽  
Jin-Mei Jiang ◽  
Xiao-Ping Long ◽  
Li-Hu Xie
Keyword(s):  
Extracellular Matrix ◽  
Cell Viability ◽  
Cell Injury ◽  
Tissue Injury ◽  
Cartilage Injury ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Western Blots

Abstract Objectives Present study aimed to illustrate the role of miR-144-3p in RA. Methods N1511 chondrocytes were stimulated by IL-1β to mimic RA injury model in vitro. Rats were subjected to injection of type II collagen to establish an in vivo RA model and the arthritis index score was calculated. Cell viability was determined by CCK-8. The expression of cartilage extracellular matrix proteins (Collagen II and Aggrecan) and matrix metalloproteinases protein (MMP-13) were determined by qRT-PCR and western blots. Cell apoptosis was measured by Flow cytometry. ELISA was applied to test the secretion of pro-inflammatory cytokines (IL-1β and TNF-α). Tissue injury and apoptosis were detected by HE staining and TUNEL staining. Interaction of miR-144-3p and BMP2 was verified by dual luciferase assay. Results MiR-144-3p was dramatically increased in IL-1β induced N1511 cells. MiR-144-3p depletion elevated cell viability, suppressed apoptosis, pro-inflammatory cytokine releasing, and extracellular matrix loss in IL-1β induced N1511 cells. Moreover, miR-144-3p targeted BMP2 to modulate its expression negatively. Activation of PI3K/Akt signaling compromised inhibition of BMP2 induced aggravated N1511 cell injury with IL-1β stimulation. Inhibition of miR-144-3p alleviated cartilage injury and inflammatory in RA rats. Conclusion Collectively, miR-144-3p could aggravate chondrocytes injury inflammatory response in RA via BMP2/PI3K/Akt axis.

scholarly journals Current Status of the Instructional Cues Provided by Notochordal Cells in Novel Disc Repair Strategies

2021 ◽  
Vol 23 (1) ◽  
pp. 427
Author(s):  
Ajay Matta ◽  
William Mark Erwin
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Current Status ◽  
Scientific Publications ◽  
Seminal Paper ◽  
Notochordal Cell ◽  
Notochordal Cells ◽  
Disc Repair

Numerous publications over the past 22 years, beginning with a seminal paper by Aguiar et al., have demonstrated the ability of notochordal cell-secreted factors to confer anabolic effects upon intervertebral disc (IVD) cells. Since this seminal paper, other scientific publications have demonstrated that notochordal cells secrete soluble factors that can induce anti-inflammatory, pro-anabolic and anti-cell death effects upon IVD nucleus pulposus (NP) cells in vitro and in vivo, direct human bone marrow-derived mesenchymal stem cells toward an IVD NP-like phenotype and repel neurite ingrowth. More recently these factors have been characterized, identified, and used therapeutically to induce repair upon injured IVDs in small and large pre-clinical animal models. Further, notochordal cell-rich IVD NPs maintain a stable, healthy extracellular matrix whereas notochordal cell-deficient IVDs result in a biomechanically and extracellular matrix defective phenotype. Collectively this accumulating body of evidence indicates that the notochordal cell, the cellular originator of the intervertebral disc holds vital instructional cues to establish, maintain and possibly regenerate the intervertebral disc.

scholarly journals ENERGY SUPPLY AND DEMAND IN THE INTERVERTEBRAL DISC

2018 ◽  
Vol 17 (3) ◽  
pp. 237-239
Author(s):  
Liudmila Andreevna Bardonova ◽  
Omar Sheikh ◽  
Irina Olegovna Malova ◽  
Vladimir Alexeevich Sorokovikov ◽  
Vadim Anatolyevich Byvaltsev
Keyword(s):  
Intervertebral Disc ◽  
Energy Supply ◽  
Cell Metabolism ◽  
Supply And Demand ◽  
Cell Activity ◽  
Nucleus Pulposus Cell ◽  
Nutrient Supply ◽  
The Body ◽  
Ivd Degeneration ◽  
Cell Phenotypes

ABSTRACT The intervertebral disc (IVD) is one of the parts of the body most commonly affected by disease, and it is only recently that we have come closer to understanding the reasons for its degeneration, in which nutrient supply plays a crucial role. In this literature review, we discuss the basic principles and characteristics of energy supply and demand to the IVD. Specifically, we review how different metabolites influence IVD cell activity, the effects of mechanical loading on IVD cell metabolism, and differences in energy metabolism of the annulus fibrous and nucleus pulposus cell phenotypes. Determining the factors that influence nutrient supply and demand in the IVD will enhance our understanding of the IVD pathology, and help to elucidate new therapeutic targets for IVD degeneration treatment.

The Role of Cardiac Fibroblasts in Extracellular Matrix-Mediated Signaling During Normal and Pathological Cardiac Development

2013 ◽  
Vol 135 (7) ◽  
Author(s):  
Kelly Elizabeth Sullivan ◽  
Lauren Deems Black
Keyword(s):  
Extracellular Matrix ◽  
Cardiac Development ◽  
Cardiac Fibroblasts ◽  
Heart Defects ◽  
Critical Role ◽  
Heart Tissue ◽  
Physical And Chemical

The extracellular matrix is no longer considered a static support structure for cells but a dynamic signaling network with the power to influence cell, tissue, and whole organ physiology. In the myocardium, cardiac fibroblasts are the primary cell type responsible for the synthesis, deposition, and degradation of matrix proteins, and they therefore play a critical role in the development and maintenance of functional heart tissue. This review will summarize the extensive research conducted in vivo and in vitro, demonstrating the influence of both physical and chemical stimuli on cardiac fibroblasts and how these interactions impact both the extracellular matrix and, by extension, cardiomyocytes. This work is of considerable significance, given that cardiovascular diseases are marked by extensive remodeling of the extracellular matrix, which ultimately impairs the functional capacity of the heart. We seek to summarize the unique role of cardiac fibroblasts in normal cardiac development and the most prevalent cardiac pathologies, including congenital heart defects, hypertension, hypertrophy, and the remodeled heart following myocardial infarction. We will conclude by identifying existing holes in the research that, if answered, have the potential to dramatically improve current therapeutic strategies for the repair and regeneration of damaged myocardium via mechanotransductive signaling.

scholarly journals The PrpC Serine-Threonine Phosphatase and PrkC Kinase Have Opposing Physiological Roles in Stationary-Phase Bacillus subtilis Cells

2002 ◽  
Vol 184 (22) ◽  
pp. 6109-6114 ◽  
Author(s):  
Tatiana A. Gaidenko ◽  
Tae-Jong Kim ◽  
Chester W. Price
Keyword(s):  
Bacillus Subtilis ◽  
Stationary Phase ◽  
Cell Viability ◽  
Cell Density ◽  
Elongation Factor ◽  
Pleiotropic Effects ◽  
General Stress ◽  
Factor G

ABSTRACT Loss of the PrpC serine-threonine phosphatase and the associated PrkC kinase of Bacillus subtilis were shown to have opposite effects on stationary-phase physiology by differentially affecting cell density, cell viability, and accumulation of β-galactosidase from a general stress reporter fusion. These pleiotropic effects suggest that PrpC and PrkC have important regulatory roles in stationary-phase cells. Elongation factor G (EF-G) was identified as one possible target of the PrpC and PrkC pair in vivo, and purified PrpC and PrkC manifested the predicted phosphatase and kinase activities against EF-G in vitro.

scholarly journals Modulation of Synthetic Tracheal Grafts with Extracellular Matrix Coatings

2021 ◽  
Vol 8 (8) ◽  
pp. 116
Author(s):  
Lumei Liu ◽  
Sayali Dharmadhikari ◽  
Robert A. Pouliot ◽  
Michael M. Li ◽  
Peter M. Minneci ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Extracellular Matrix ◽  
Cell Viability ◽  
Dependent Manner ◽  
Orthotopic Implantation ◽  
Synthetic Scaffolds ◽  
Cell Biocompatibility ◽  
Dose Dependent

Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates (pECM and hECM) were created through the decellularization and lyophilization of lung tissue. Four concentrations of pECM and hECM coatings on syn-TG were characterized for their effects on scaffold morphologies and on in vitro cell viability and growth. Uncoated and ECM-coated syn-TG were subsequently evaluated in vivo through the orthotopic implantation of segmental grafts or patches. These studies demonstrated that ECM coatings were not cytotoxic and, enhanced the in vitro cell viability and growth on syn-TG in a dose-dependent manner. Mass spectrometry demonstrated that fibrillin, collagen, laminin, and nephronectin were the predominant ECM components transferred onto scaffolds. The in vivo results exhibited similar robust epithelialization of uncoated and coated syn-TG patches; however, the epithelialization remained poor with either uncoated or coated scaffolds in the segmental replacement models. Overall, these findings demonstrated that ECM coatings improve the seeded cell biocompatibility of synthetic scaffolds in vitro; however, they do not improve graft epithelialization in vivo.

scholarly journals Repetitive in vivo manual loading of the spine elicits cellular responses in porcine annuli fibrosi

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248104
Author(s):  
John Robert Matyas ◽  
Claudia Klein ◽  
Dragana Ponjevic ◽  
Neil A. Duncan ◽  
Gregory N. Kawchuk
Keyword(s):  
Intervertebral Disc ◽  
Manual Therapy ◽  
Cellular Response ◽  
Cell Metabolism ◽  
Low Frequency ◽  
Intervertebral Discs ◽  
Disc Cell ◽  
Therapy Interventions ◽  
Pathway Analyses

Back pain and intervertebral disc degeneration are prevalent, costly, and widely treated by manual therapies, yet the underlying causes of these diseases are indeterminate as are the scientific bases for such treatments. The present studies characterize the effects of repetitive in vivo manual loads on porcine intervertebral disc cell metabolism using RNA deep sequencing. A single session of repetitive manual loading applied to the lumbar spine induced both up- and down-regulation of a variety of genes transcribed by cells in the ventral annuli fibrosi. The effect of manual therapy at the level of loading was greater than at a level distant to the applied load. Gene ontology and molecular pathway analyses categorized biological, molecular, and cellular functions influenced by repetitive manual loading, with over-representation of membrane, transmembrane, and pericellular activities. Weighted Gene Co-expression Network Analysis discerned enrichment in genes in pathways of inflammation and skeletogenesis. The present studies support previous findings of intervertebral disc cell mechanotransduction, and are the first to report comprehensively on the repertoire of gene targets influenced by mechanical loads associated with manual therapy interventions. The present study defines the cellular response of repeated, low-amplitude loads on normal healthy annuli fibrosi and lays the foundation for future work defining how healthy and diseased intervertebral discs respond to single or low-frequency manual loads typical of those applied clinically.

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