Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular pathology of human knee arthrofibrosis defined by RNA sequencing.

ABSTRACT: Arthrofibrosis is an abnormal histopathologic response, is debilitating for patients, and poses a substantial unsolved clinical challenge. This study characterizes molecular biomarkers and regulatory pathways associated with arthrofibrosis by comparing fibrotic and non-fibrotic human knee tissue. The fibrotic group encompasses 4 patients undergoing a revision total knee arthroplasty (TKA) for arthrofibrosis (RTKA-A) while the non-fibrotic group includes 4 patients undergoing primary TKA for osteoarthritis (PTKA) and 4 patients undergoing revision TKA for non-arthrofibrotic and non-infectious etiologies (RTKA-NA). RNA-sequencing of posterior capsule specimens revealed differences in gene expression between each patient group by hierarchical clustering, principal component analysis, and correlation analyses. Multiple differentially expressed genes (DEGs) were defined in RTKA-A versus PTKA patients (i.e., 2059 up-regulated and 1795 down-regulated genes) and RTKA-A versus RTKA-NA patients (i.e., 3255 up-regulated and 3683 down-regulated genes). Our findings define molecular and pathological markers of arthrofibrosis, as well as novel potential targets for risk profiling, early diagnosis and pharmacological treatment of patients.

SUBMITTER: Bayram B

PROVIDER: S-EPMC7217749 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Molecular Pathology of Human Knee Arthrofibrosis Defined by RNA Sequencing

Project description:This study aims to compare the genetic profile of fibrotic and non-fibrotic human knee capsular tissue in an effort to identify possible molecular pathways responsible for the development of AF. RNA sequencing (RNA-seq) and bioinformatics were used to define differentially expressed genes (DEGs) and molecular pathways linked to joint stiffening. Gene expression profiling revealed a distinct clustering of each patient group by principal component analysis, hierarchical clustering and similarity matrix analysis. Three prospectively-collected, matched patient cohorts were used to formally describe gene expression signatures of AF patients. The findings define molecular and pathological markers of AF, as well as novel potential targets for pre-diagnosis and pharmacological treatment of AF patients.

2020-01-01 | GSE135854 | GEO

Molecular Pathology of Human Knee Arthrofibrosis Defined by RNA Sequencing

Project description:Molecular Pathology of Human Knee Arthrofibrosis Defined by RNA Sequencing

| PRJNA560339 | ENA

Molecular pathology of total knee arthroplasty instability defined by RNA-seq.

Project description:Total knee arthroplasty (TKA) is a durable and reliable procedure to alleviate pain and improve joint function. However, failures related to flexion instability sometimes occur. The goal of this study was to define biological differences between tissues from patients with and without flexion instability of the knee after TKA. Human knee joint capsule tissues were collected at the time of primary or revision TKAs and analyzed by RT-qPCR and RNA-seq, revealing novel patterns of differential gene expression between the two groups. Interestingly, genes related to collagen production and extracellular matrix (ECM) degradation were higher in samples from patients with flexion instability. Partitioned clustering analyses further emphasized differential gene expression patterns between sample types that may help guide clinical interpretations of this complication. Future efforts to disentangle the effects of physical and biological (e.g., transcriptomic modifications) risk factors will aid in further characterizing and avoiding flexion instability after TKA.

| S-EPMC5963991 | biostudies-literature

Molecular pathology of adverse local tissue reaction caused by metal-on-metal implants defined by RNA-seq.

Project description:Total hip arthroplasty (THA) alleviates hip pain and improves joint function. Current implant design permits long-term survivorship of THAs, but certain metal-on-metal (MoM) articulations can portend catastrophic failure due to adverse local tissue reactions (ALTR). Here, we identified biological and molecular differences between periacetabular synovial tissues of patients with MoM THA failure undergoing revision THA compared to patients undergoing primary THA for routine osteoarthritis (OA). Analysis of tissue biopsies by RNA-sequencing (RNA-seq) revealed that MoM patient samples exhibit significantly increased expression of immune response genes but decreased expression of genes related to extracellular matrix (ECM) remodeling. Thus, interplay between local tissue inflammation and ECM degradation may account for the pathology and compromised clinical outcomes in select patients with MoM implants. We conclude that adverse responses of host tissues to implant materials result in transcriptomic modifications in patients with MoM implants that permit consideration of strategies that could mitigate ECM damage.

| S-EPMC6428632 | biostudies-literature

Human xylosyltransferases--mediators of arthrofibrosis? New pathomechanistic insights into arthrofibrotic remodeling after knee replacement therapy.

Project description:Total knee replacement (TKR) is a common therapeutic option to restore joint functionality in chronic inflammatory joint diseases. Subsequent arthrofibrotic remodeling occurs in 10%, but the underlying pathomechanisms remain unclear. We evaluated the association of xylosyltransferases (XT), fibrotic mediators catalyzing glycosaminoglycan biosynthesis, leading to arthrofibrosis as well as the feasibility of using serum XT activity as a diagnostic marker. For this purpose, synovial fibroblasts (SF) were isolated from arthrofibrotic and control synovial biopsies. Basal α-smooth muscle actin expression revealed a high fibroblast-myofibroblast transition rate in arthrofibrotic fibroblasts. Fibrotic remodeling marked by enhanced XT activity, α-SMA protein expression as well as xylosyltransferase-I, collagen type III-alpha-1 and ACTA2 mRNA expression was stronger in arthrofibrotic than in control fibroblasts treated with transforming growth factor-β1 (TGF-β1). Otherwise, no differences between serum levels of XT-I activity or common fibrosis markers (galectin-3 and growth differentiation factor-15 levels (GDF-15)) were found between 95 patients with arthrofibrosis and 132 controls after TKR. In summary, XT-I was initially investigated as a key cellular mediator of arthrofibrosis and a target for therapeutic intervention. However, the blood-synovial-barrier makes arthrofibrotic molecular changes undetectable in serum. Future studies on monitoring or preventing arthrofibrotic remodeling should therefore rely on local instead of systemic parameters.

| S-EPMC4517395 | biostudies-other

The transcriptional landscape of the yeast genome defined by RNA sequencing.

Project description:The identification of untranslated regions, introns, and coding regions within an organism remains challenging. We developed a quantitative sequencing-based method called RNA-Seq for mapping transcribed regions, in which complementary DNA fragments are subjected to high-throughput sequencing and mapped to the genome. We applied RNA-Seq to generate a high-resolution transcriptome map of the yeast genome and demonstrated that most (74.5%) of the nonrepetitive sequence of the yeast genome is transcribed. We confirmed many known and predicted introns and demonstrated that others are not actively used. Alternative initiation codons and upstream open reading frames also were identified for many yeast genes. We also found unexpected 3'-end heterogeneity and the presence of many overlapping genes. These results indicate that the yeast transcriptome is more complex than previously appreciated.

| S-EPMC2951732 | biostudies-other

Arthroscopic Lysis of Adhesions for Treatment of Post-traumatic Arthrofibrosis of the Knee Joint.

Project description:Normal knee range of motion varies slightly between individuals and measures approximately 0° to -5° of extension to 140° of flexion. A full arc of motion is required for normal gait and knee function. Loss of normal joint range of motion may occur after a traumatic knee injury and may contribute to increased pain, lower functional outcome scores, and decreased patient satisfaction. Although multiple factors may contribute to the development of motion loss, the occurrence of intra-articular scar tissue adhesions, or post-traumatic arthrofibrosis, may limit the patient's knee motion in the early postoperative period. Once motion loss has been identified, it can be a challenging complication to manage. Arthroscopic lysis of adhesions with manipulation under anesthesia is a reliable surgical technique that can improve range of motion in patients with knee stiffness due to post-traumatic arthrofibrosis.

| S-EPMC5800957 | biostudies-literature

A potential mode of action for Anakinra in patients with arthrofibrosis following total knee arthroplasty.

Project description:Arthrofibrosis is a fibroproliferative disease characterised by excessive deposition of extracellular matrix components intra-articularly leading to pain and restricted range of movement. Although frequently observed following total knee arthroplasty (TKA) no therapeutic options exist. A pilot study demonstrated that intra-articular injection of Anakinra, an IL-1R antagonist, improved range of movement and pain in patients with arthrofibrosis however the mechanism of action is unknown. We hypothesise that IL-1α/β will drive an inflammatory phenotype in fibroblasts isolated from the knee, therefore identifying a potential mechanism of action for Anakinra in arthrofibrosis following TKA. Fibroblasts isolated from synovial membranes and infra-patellar fat pad of patients undergoing TKA express high levels of IL-1R1. Stimulation with IL-1α/β induced a pro-inflammatory phenotype characterised by increased secretion of GMCSF, IL-6 and IL-8. No significant difference in the inflammatory response was observed between fibroblasts isolated from synovial membrane or infra-patellar fat pad. IL-1α/β treatments induced a pro-inflammatory phenotype in fibroblasts from both synovial membrane and infra-patellar fat pad and therefore Anakinra can likely have an inhibitory effect on fibroblasts present in both tissues in vivo. It is also likely that fibroblast responses in the tissues are controlled by IL-1α/β availability and not their ability to respond to it.

| S-EPMC4639732 | biostudies-literature

Identification of novel biomarkers for arthrofibrosis after total knee arthroplasty in animal models and clinical patients.

Project description:BackgroundArthrofibrosis is a debilitating complication after total knee arthroplasty (TKA) which becomes a considerable burden for both patients and clinical practitioners. Our study aimed to identify novel biomarkers and therapeutic targets for drug discovery.MethodsPotential biomarker genes were identified based on bioinformatic analysis. Twelve male New Zealand white rabbits underwent surgical fixation of unilateral knees to mimics the joint immobilization of the clinical scenario after TKA surgery. Macroscopic assessment, hydroxyproline content determination, and histological analysis of tissue were performed separately after 3-days, 1-week, 2-weeks, and 4-weeks of fixation. We also enrolled 46 arthrofibrosis patients and 92 controls to test the biomarkers. Clinical information such as sex, age, range of motion (ROM), and visual analogue scale (VAS) was collected by experienced surgeons FINDINGS: Base on bioinformatic analysis, transforming growth factor-beta receptor 1 (TGFBR1) was identified as the potential biomarkers. The level of TGFBR1 was significantly raised in the rabbit synovial tissue after 4-weeks of fixation (p<0.05). TGFBR1 also displayed a highly positive correlation with ROM loss and hydroxyproline contents in the animal model. TGFBR1 showed a significantly higher expression level in arthrofibrosis patients with a receiver operating characteristic (ROC) area under curve (AUC) of 0.838. TGFBR1 also performed positive correlations with VAS baseline (0.83) and VAS after 1 year (0.76) while negatively correlated with ROM baseline (-0.76) in clinical patients.InterpretationOur findings provided novel biomarkers for arthrofibrosis diagnosis and uncovered the role of TGFBR1. This may contribute to arthrofibrosis prevention and therapeutic drug discovery.FundingNone.

| S-EPMC8325099 | biostudies-literature

The STAK tool: evaluation of a new device to treat arthrofibrosis and poor range of movement following total knee arthroplasty and major knee surgery.

Project description:Aims:This study aims to evaluate a new home medical stretching device called the Self Treatment Assisted Knee (STAK) tool to treat knee arthrofibrosis. Methods:35 patients post-major knee surgery with arthrofibrosis and mean range of movement (ROM) of 68° were recruited. Both the STAK intervention and control group received standard physiotherapy for eight weeks, with the intervention group additionally using the STAK at home. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Scores (OKS) were collected at all timepoints. An acceptability and home exercise questionnaire capturing adherence was recorded after each of the interventions. Results:Compared to the control group, the STAK intervention group made significant gains in mean ROM (30° versus 8°, p < 0.0005), WOMAC (19 points versus 3, p < 0.0005), and OKS (8 points versus 3, p < 0.0005). The improvements in the STAK group were maintained at long-term follow-up. No patients suffered any complications relating to the STAK, and 96% of patients found the STAK tool 'perfectly acceptable'. Conclusion:The STAK tool is effective in increasing ROM and reducing pain and stiffness. Patients find it acceptable and adherence to treatment was high. This study indicates that the STAK tool would be of benefit in clinical practice and may offer a new, cost-effective treatment for arthrofibrosis.Cite this article: Bone Joint Open 2020;1-8:465-473.

| S-EPMC7667223 | 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