Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exploring the Crosstalk between Hydrostatic Pressure and Adipokines: An In Vitro Study on Human Osteoarthritic Chondrocytes.

ABSTRACT: Obesity is a risk factor for osteoarthritis (OA) development and progression due to an altered biomechanical stress on cartilage and an increased release of inflammatory adipokines from adipose tissue. Evidence suggests an interplay between loading and adipokines in chondrocytes metabolism modulation. We investigated the role of loading, as hydrostatic pressure (HP), in regulating visfatin-induced effects in human OA chondrocytes. Chondrocytes were stimulated with visfatin (24 h) and exposed to high continuous HP (24 MPa, 3 h) in the presence of visfatin inhibitor (FK866, 4 h pre-incubation). Apoptosis and oxidative stress were detected by cytometry, B-cell lymphoma (BCL)2, metalloproteinases (MMPs), type II collagen (Col2a1), antioxidant enzymes, miRNA, cyclin D1 expressions by real-time PCR, and β-catenin protein by western blot. HP exposure or visfatin stimulus significantly induced apoptosis, superoxide anion production, and MMP-3, -13, antioxidant enzymes, and miRNA gene expression, while reducing Col2a1 and BCL2 mRNA. Both stimuli significantly reduced β-catenin protein and increased cyclin D1 gene expression. HP exposure exacerbated visfatin-induced effects, which were counteracted by FK866 pre-treatment. Our data underline the complex interplay between loading and visfatin in controlling chondrocytes' metabolism, contributing to explaining the role of obesity in OA etiopathogenesis, and confirming the importance of controlling body weight for disease treatment.

SUBMITTER: Cheleschi S

PROVIDER: S-EPMC7963177 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes.

Project description:Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1-5 MPa) and continuous static HP (10 MPa) for 3 hrs. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and ?-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. ?-catenin protein expression was reduced in cells exposed to HP 1-5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/?-catenin pathway.

| S-EPMC7279254 | biostudies-literature

Comparing effects of perfusion and hydrostatic pressure on human chondrocytes using gene profiles

Project description:Hydrostatic pressure and perfusion have been shown to alter the chondrogenic potential of articular chondrocytes. In order to compare the effects of hydrostatic pressure plus perfusion (HPP) and perfusion (P) we investigated the complete gene expression profiles of human chondrocytes under HPP and P. A simplified bioreactor was constructed applying loading (0.1 MPa for 2 h) and perfusion (2ml) through the same piping by pressurizing the medium directly. High-density monolayer cultures of human chondrocytes were exposed to HPP or P for 4 days. Controls were maintained in static culture. Gene expression was evaluated by sequencing (RNAseq) and quantitative real-time PCR analysis. RNAseq identified similarities between the two treatments. Specifically, HPP and P increased COL2A1 expression and decreased COL1A1 and MMP-13 expression. Despite of the similarities, RNAseq revealed a list of cartilage genes including ACAN, ITGA10 and TNC, which were differentially expressed by HPP and P. Of these candidates adhesion related molecules were found to be upregulated in HPP. Both HPP and P treatment had beneficial effects on chondrocyte differentiation and decreased catabolic enzyme expression. The study provides new insight into how hydrostatic pressure and perfusion enhance cartilage differentiation and inhibit catabolic effects

2016-03-21 | GSE69206 | GEO

Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures.

Project description:Osteoarthritis (OA) is one of the most common causes of disability and represents a major socio-economic burden. Despite intensive research, the molecular mechanisms responsible for the initiation and progression of OA remain inconclusive. In recent years experimental findings revealed elevated levels of reactive oxygen species (ROS) as a major factor contributing to the onset and progression of OA. Hence, we designed a hydrostatic pressure bioreactor system that is capable of stimulating cartilage cell cultures with elevated ROS levels. Increased ROS levels in the media did not only lead to an inhibition of glycosaminoglycans and collagen II formation but also to a reduction of already formed glycosaminoglycans and collagen II in chondrogenic mesenchymal stem cell pellet cultures. These effects were associated with the elevated activity of matrix metalloproteinases as well as the increased expression of several inflammatory cytokines. ROS activated different signaling pathways including PI3K/Akt and MAPK/ERK which are known to be involved in OA initiation and progression. Utilizing the presented bioreactor system, an OA in vitro model based on the generation of ROS was developed that enables the further investigation of ROS effects on cartilage degradation but can also be used as a versatile tool for anti-oxidative drug testing.

| S-EPMC6242959 | biostudies-literature

Effect of electromagnetic fields on human osteoarthritic and non-osteoarthritic chondrocytes.

Project description:Studies of the effects of electromagnetic fields (EMFs) on cartilaginous cells show a broad range of outcomes. However EMFs are not yet clinically applied as standard treatment of osteoarthritis, as EMF effects are showing varying outcomes in the literature. The aim of this study was to examine effects of EMFs (5 mT or 8 mT) on osteoarthritic (OA) and non-OA chondrocytes in order to investigate whether EMF effects are related to chondrocyte and EMF quality.Pellets of human OA and non-OA chondrocytes were exposed to a sinusoidal 15 Hz EMF produced by a solenoid. Control groups were cultivated without EMF under standard conditions for 7 days. Cultures were examined by staining, immunohistochemistry and quantitative real-time PCR for RNA corresponding to cartilage specific proteins (COL2A1, ACAN, SOX9).OA chondrocytes increased the expression of COL2A1 and ACAN under 5 mT EMF compared to control. In contrast no changes in gene expression were observed in non-OA chondrocytes. OA and non-OA chondrocytes showed no significant changes in gene expression under 8 mT EMF.A 5 mT EMF increased the expression of cartilage specific genes in OA chondrocytes whereas in non-OA chondrocytes no changes in gene expression were observed. An 8 mT EMF however showed no effect altogether. This suggests that EMF effects are related to EMF but also to chondrocyte quality. Further studies about the clinical relevance of this effect are necessary.

| S-EPMC5556359 | biostudies-other

High hydrostatic pressure induces pro-osteoarthritic changes in cartilage precursor cells: A transcriptome analysis.

Project description:Due to the high water content of cartilage, hydrostatic pressure is likely one of the main physical stimuli sensed by chondrocytes. Whereas, in the physiological range (0 to around 10 MPa), hydrostatic pressure exerts mostly pro-chondrogenic effects in chondrocyte models, excessive pressures have been reported to induce detrimental effects on cartilage, such as increased apoptosis and inflammation, and decreased cartilage marker expression. Though some genes modulated by high pressure have been identified, the effects of high pressure on the global gene expression pattern have still not been investigated. In this study, using microarray technology and real-time PCR validation, we analyzed the transcriptome of ATDC5 chondrocyte progenitors submitted to a continuous pressure of 25 MPa for up to 24 h. Several hundreds of genes were found to be modulated by pressure, including some not previously known to be mechano-sensitive. High pressure markedly increased the expression of stress-related genes, apoptosis-related genes and decreased that of cartilage matrix genes. Furthermore, a large set of genes involved in the progression of osteoarthritis were also induced by high pressure, suggesting that hydrostatic pressure could partly mimic in vitro some of the genetic alterations occurring in osteoarthritis.

| S-EPMC5558982 | biostudies-literature

Toll-like receptors in human chondrocytes and osteoarthritic cartilage.

Project description:Background and purposeDegenerating cartilage releases potential danger signals that react with Toll-like receptor (TLR) type danger receptors. We investigated the presence and regulation of TLR1, TLR2, and TLR9 in human chondrocytes.MethodsWe studied TLR1, TLR2, TLR4, and TLR9 mRNA (qRT-PCR) and receptor proteins (by immunostaining) in primary mature healthy chondrocytes, developing chondrocytes, and degenerated chondrocytes in osteoarthritis (OA) tissue sections of different OARSI grades. Effects of a danger signal and of a pro-inflammatory cytokine on TLRs were also studied.ResultsIn primary 2D-chondrocytes, TLR1 and TLR2 were strongly expressed. Stimulation of 2D and 3D chondrocytes with a TLR1/2-specific danger signal increased expression of TLR1 mRNA 1.3- to 1.8-fold, TLR2 mRNA 2.6- to 2.8-fold, and TNF-? mRNA 4.5- to 9-fold. On the other hand, TNF-? increased TLR1 mRNA] expression 16-fold, TLR2 mRNA expression 143- to 201-fold, and TNF-? mRNA expression 131- to 265-fold. TLR4 and TLR9 mRNA expression was not upregulated. There was a correlation between worsening of OA and increased TLR immunostaining in the superficial and middle cartilage zones, while chondrocytes assumed a CD166(×) progenitor phenotype. Correspondingly, TLR expression was high soon after differentiation of mesenchymal stem cells to chondrocytes. With maturation, it declined (TLR2, TLR9).InterpretationMature chondrocytes express TLR1 and TLR2 and may react to cartilage matrix/chondrocyte-derived danger signals or degradation products. This leads to synthesis of pro-inflammatory cytokines, which stimulate further TLR and cytokine expression, establishing a vicious circle. This suggests that OA can act as an autoinflammatory disease and links the old mechanical wear-and-tear concept with modern biochemical views of OA. These findings suggest that the chondrocyte itself is the earliest and most important inflammatory cell in OA.

| S-EPMC3851674 | biostudies-literature

CCN4/WISP1 Promotes Migration of Human Primary Osteoarthritic Chondrocytes.

Project description:ObjectivesPreviously, we have shown the involvement of cellular communication network factor 4/Wnt-activated protein Wnt-1-induced signaling protein 1 (CCN4/WISP1) in osteoarthritic (OA) cartilage and its detrimental effects on cartilage. Here, we investigated characteristics of CCN4 in chondrocyte biology by exploring correlations of CCN4 with genes expressed in human OA cartilage with functional follow-up.DesignSpearman correlation analysis was performed for genes correlating with CCN4 using our previously established RNA sequencing dataset of human preserved OA cartilage of the RAAK study, followed by a pathway enrichment analysis for genes with ρ ≥|0.6.| Chondrocyte migration in the absence or presence of CCN4 was determined in a scratch assay, measuring scratch size using a live cell imager for up to 36 h. Changes in expression levels of 12 genes, correlating with CCN4 and involved in migratory processes, were determined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsCorrelation of CCN4 with ρ ≥|0.6| was found for 58 genes in preserved human OA cartilage. Pathway analysis revealed "neural crest cell migration" as most significant enriched pathway, containing among others CORO1C, SEMA3C, and SMO. Addition of CCN4 to primary chondrocytes significantly enhance chondrocyte migration as demonstrated by reduced scratch size over the course of 36 h, but at the timepoints measured no effect was observed on mRNA expression of the 12 genes.ConclusionCCN4 increases cell migration of human primary OA chondrocytes. Since WISP1 expression is known to be increased in OA cartilage, this may serve to direct chondrocytes toward cartilage defects and orchestrate repair.

| S-EPMC10076902 | biostudies-literature

Exploring Hydrothermal Synthesis of SAPO-18 under High Hydrostatic Pressure.

Project description:The effect of external hydrostatic pressure on the hydrothermal synthesis of the microporous silicoaluminophosphate SAPO-18 has been explored. The crystallization of the SAPO-18 phase is inhibited at 150 °C under high pressures (200 MPa) when using relatively diluted synthesis mixtures. On the contrary, the use of concentrated synthesis mixtures allowed SAPO-18 to be obtained in all the studied conditions. The obtained solids were characterized with XRD, SEM, ICP-AES, TG and 27Al and 31P MAS NMR spectroscopy. The results highlight the importance of the external pressure effect on the hydrothermal synthesis of molecular sieves and its influence on the interaction between the organic molecule and the silicoaluminophosphate network.

| S-EPMC8838306 | biostudies-literature

Optimization of Extracellular Matrix Synthesis and Accumulation by Human Articular Chondrocytes in 3-Dimensional Construct with Repetitive Hydrostatic Pressure.

Project description:Objective The effects of hydrostatic pressure (HP) on the matrix synthesis by human articular chondrocytes have been reported elsewhere. In order to optimize the production of extracellular matrix, we aimed to clarify the effects of repetitive HP on metabolic function by human articular chondrocytes. Design The human articular chondrocytes were expanded and embedded within a collagen gel/sponge scaffold. We incubated these constructs with and without HP followed by atmospheric pressure (AP) and repeated the second HP followed by AP over 14 days. Genomic, biochemical, and histological evaluation were performed to compare the effects of each regimen on the constructs. Results The gene expressions of collagen type II and aggrecan core protein were significantly upregulated with repetitive HP regimens compared with a single HP or AP by 14 days ( P < 0.01 or 0.05). Matrix metalloptoteinase-13 (MMP-13) in AP was upregulated significantly compared to other HP regimens at day 14 ( P < 0.01). No significant difference was observed in tissue inhibitor of metalloproteinases-II. Immunohistology demonstrated that application of HP (both repetitive and single) promoted the accumulation of specific extracellular matrix and reduced a MMP-13. A single regimen of HP followed by AP significantly increased the amount of sulfated glycosaminoglycan than that of the AP, whereas repetitive HP remained similar level of that of the AP. Conclusions Repetitive HP had a greater effect on anabolic activity by chondrocytes than a single HP regimen, which will be advantageous for producing a matrix-rich cell construct.

| S-EPMC5871128 | biostudies-literature

Targeting Human Osteoarthritic Chondrocytes with Ligand Directed Bacteriophage-Based Particles.

Project description:Osteoarthritis (OA) is a degenerative joint disease characterized by progressive deterioration and loss of articular cartilage. There is currently no treatment to reverse the onset of OA. Thus, we developed a targeted delivery strategy to transfer genes into primary human chondrocytes as a proof-of-concept study. We displayed a chondrocyte-affinity peptide (CAP) on the pIII minor coat protein of the M13 filamentous bacteriophage (phage)-based particle carrying a mammalian transgene cassette under cytomegalovirus CMV promoter and inverted terminal repeats (ITRs) cis elements of adeno-associated virus serotype 2 (AAV-2). Primary human articular chondrocytes (HACs) were used as an in vitro model, and the selectivity and binding properties of the CAP ligand in relation to the pathogenic conditions of HACs were characterized. We found that the CAP ligand is highly selective toward pathogenic HACs. Furthermore, the stability, cytotoxicity, and gene delivery efficacy of the CAP-displaying phage (CAP.Phage) were evaluated. We found that the phage particle is stable under a wide range of temperatures and pH values, while showing no cytotoxicity to HACs. Importantly, the CAP.Phage particle, carrying a secreted luciferase (Lucia) reporter gene, efficiently and selectively delivered transgene expression to HACs. In summary, it was found that the CAP ligand preferably binds to pathogenic chondrocytes, and the CAP.Phage particle successfully targets and delivers transgene to HACs.

| S-EPMC8706358 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data