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Delivery of a tissue derived extracellular matrix gel modulates early fibro-adipogenic cell behavior and improves recovery following both acute and chronic disuse muscle injury.

ABSTRACT: To evaluate decellularized skeletal muscle extracellular matrix hydrogel effectiveness in treating shoulder cuff tears using a rabbit (RI) model. Male New Zealand white rabbits had supraspinatus tendon severed and were housed for 12 weeks, after which they had tendon reattached and half of rabbits also received an extracellular matrix gel injection. We then performed gene expression profiling analysis using data obtained from RNA-seq from rabbit supraspinatus muscles (n=5 for repair+gel treatment, n=5 for repair only treatment , n=4 for injured control) at 2 weeks post and (n=5 for repair+gel treatment, n=5 for repair only treatment , n=5 for uninjured control) at 12 weeks post treatment

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE221331 | GEO | 2022/12/30

REPOSITORIES: GEO

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Transcriptional Changes Associated with rotator cuff repair

Project description:In this study, we collected rabbit supraspinatus muscle tissue with higher temporal resolution (1, 2, 4, 8 weeks)after 8 wk tear followed by repair (n=4/group), to determine time-depenet transcriptional changes after repair. RNA sequencing and analyses were performed using standard techniques to identify a transcriptional timeline of rotator cuff muscle changes and related morphological sequelae.

2023-04-26 | GSE186320 | GEO

A quantitative label-free analysis of the extracellular proteome of human supraspinatus reveals damage to the pericellular and elastic fibre niches in torn and aged tendons

Project description:Tears of the human supraspinatus tendon are common and often cause painful and debilitating loss of function. Progressive failure of the tendon leading to structural abnormality and tearing is accompanied by numerous cellular and extra-cellular matrix (ECM) changes in the tendon tissue. This proteomics study aimed to compare torn and aged rotator cuff tissue to young and healthy tissue, and provide the first ECM inventory of human supraspinatus tendon generated using label-free quantitative LC-MS/MS. Employing two digestion protocols (trypsin and elastase), we analysed grain-sized tendon supraspinatus biopsies from older patients with torn tendons and from young controls. Our findings confirm measurable degradation of collagen fibrils and associated proteins in old and torn tendons, suggesting a significant loss of tissue organisation. A particularly marked reduction of cartilage oligomeric matrix protein (COMP) raises the possibility of using changes in levels of this glycoprotein as a marker of abnormal tissue, as previously suggested in horse models. Surprisingly, and despite using an elastase digestion for validation, elastin was not detected, raising the possibility that it is not highly abundant in human supraspinatus tendon. Finally, we identified marked changes to the elastic fibre, fibrillin-rich niche and the pericellular matrix. Further investigation of these regions may yield other potential biomarkers and help to explain detrimental cellular processes associated with tendon ageing and tendinopathy.

2018-07-03 | PXD006466 | Pride

Tenascin C Deletion Impairs Tendon Healing and Functional Recovery After Rotator Cuff Repair

Project description:The biological factors that affect healing after rotator cuff repair (RCR) are not well 63 understood. Genetic variants in the extracellular matrix protein Tenascin C (TNC) are associated 64 with impaired tendon healing and it is expressed in rotator cuff tendon tissue after injury, 65 suggesting it may have a role in the repair process. The purpose of the current study was to 66 determine the role of TNC on tendon healing after RCR in a murine model. The supraspinatus 67 tendon was transected and repaired on the left shoulder of Wild-Type (WT-RCR) and Tenascin 68 C null (Tnc - -RCR) mice. Controls included the unoperated, contralateral shoulder of WT-RCR 69 and Tnc - -RCR mice and unoperated shoulders from WT and Tnc - mice. We performed 70 histologic, activity testing, RNA-seq, and biomechanical analyses. At 8-weeks post-RCR, Tnc71 mice had severe bone and tendon defects following rotator cuff repair. Tnc- -RCR mice had 72 reduced activity after rotator cuff repair including reduced wheel rotations, wheel duration, and 73 wheel episode average velocity compared with WT-RCR. Loss of Tnc following RCR altered 74 gene expression in the shoulder, including upregulation of sex hormone and WNT pathways and 75 a downregulation of inflammation and cell cycle pathways. Tnc - mice had similar biomechanical 76 properties after repair as WT. Further research is required to evaluate tissue specific alterations 77 of Tnc, the interactions of Tnc and sex hormone and inflammation pathways as well as possible 78 adjuvants to improve enthesis healing in the setting of reduced TNC function.

2024-09-16 | GSE271514 | GEO

Effect of Etanercept on Active Pulmonary Tuberculosis in Rabbits

Project description:Treatment of chronic inflammatory diseases with tumor necrosis factor alpha antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared to infected untreated animals. The microarray experiments involves comparison of changes in gene expression between Mtb-HN878 infected and Etanercept treated and untreated rabbit lungs at 4 and 8 weeks post-treatment, starting at 4 weeks post-infection. New Zealand White rabbits were infected with Mtb HN878 at about 3.2log10 (on day 0). One group of rabbits were treated with Etanercept, starting at 4 weeks post-infection, for 4 or 8 weeks. Total RNA from lung tissues of treated and untreated animals were isolated at 4 and 8 weeks post treatment and used for microarray gene expression analysis.

2014-01-28 | E-GEOD-54442 | biostudies-arrayexpress

Adjunctive therapy with a phosphodiesterase-4 inhibitor improves INH response to pulmonary tuberculosis

Project description:Current antibiotic regimen to treat tuberculosis (TB) is ineffective in fully eliminating the bacterial load and in alleviating disease pathology. We examined the usefulness of a phosphodiesterase-4 inhibitor (CC-11050) as an adjunctive to anti-TB drug Isoniazid (INH) to improve the outcome of treatment in a rabbit model of active pulmonary TB. Control of Mycobacterium tuberculosis (Mtb) growth, disease pathology and the global transcriptional response in Mtb-infected lungs of rabbits with or without CC-11050 treatment were studied. The microarray experiments involves comparison of changes in gene expression between uninfected and Mtb-HN878 infected (Untreated) or CC-11050 treated rabbit lungs at 8 weeks post-treatment, starting at 4 weeks of infection (i.e, 12 weeks post infection).

2015-12-21 | GSE74687 | GEO

Effect of Etanercept on Active Pulmonary Tuberculosis in Rabbits

2014-01-28 | GSE54442 | GEO

Human Amniotic Epithelial Cell Transplantation Improves Scar Remodeling in Preclinical Model of Acute Vocal Fold Injury: A Pilot Study

Project description:Objective: To gain insight into the molecular mechanisms underlying the early stages of vocal fold extracellular matrix (ECM) remodeling after a mid-membranous injury resulting from the use of human amniotic epithelial cells (hAEC), as a novel regenerative medicine cell-based therapy. Methods: Vocal folds of six female, New Zealand White rabbits were bilaterally injured. Three rabbits had immediate bilateral direct injection of 1 x 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized six weeks after injury. Proteomic analyses (in-gel trypsin protein digestion, LC-MS/MS, protein identification using Proteome Discoverer and the Uniprot Oryctolagus cuniculus (Rabbit) proteome) and histological analyses were performed. Results: hAEC treatment significantly increased the expression of ECM proteins, elastin microfibril interface-located protein 1 (EMILIN-1) and myocilin that are primarily involved in elastogenesis of blood vessels and granulation tissue. A reactome pathway analysis showed increased activity of the anchoring fibril formation by collagen I and laminin, providing mechanical stability and activation of cell signaling pathways regulating cell function. hAEC increased the abundance of keratin 1 indicating accelerated induction of the differentiation programming of the basal epithelial cells and, thereby, improved barrier function. Lastly, upregulation of Rab GDP dissociation inhibitor indicates that hAEC activate the vesicle endocytic and exocytic pathways, supporting the exosome-mediated activation of cell-matrix and cell-to-cell interactions. Conclusions: This pilot study suggests that injection of hAEC into an injured rabbit vocal fold favorably alters ECM composition creating a microenvironment that accelerates differentiation of regenerated epithelium and promotes neovascularization indicative of accelerated repair.

2021-03-30 | MSV000087132 | MassIVE

Transcriptional Changes Associated with Acute to Chronic Stage Muscle Adaptations in a Model of Rotator Cuff Tendon Tear

Project description:In this study, we collected rabbit supraspinatus muscle tissue with higher temporal resolution (1, 2, 4, 8, 16 weeks) post-tenotomy (n=6/group), where muscle degeneration occurs at later time points, to determine if transcriptional changes occur. RNA sequencing and analyses were performed using standard techniques to identify a transcriptional timeline of rotator cuff muscle changes and related morphological sequelae.

2021-07-14 | GSE173234 | GEO

Rattus norvegicus

Project description:Gene expression in degenerated rat supraspinatus tendon

| PRJNA94413 | ENA

Genomic and lipidomic actions of nandrolone on detached rotator cuff muscle in sheep

Project description:Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied immediately after tendon release. The effects of infraspinatus tendon release and subsequent tendon repair at 16 weeks were studied in six Swiss Alpine sheep. In the interventional groups, 150mg nandrolone was administered weekly after tendon release until sacrifice (N22W, n=6) or starting at the time of repair (N6W, n=6). Infraspinatus volume, composition, expressed transcripts, lipids, and selected proteins were analyzed at baseline, 16 and 22 weeks. Tendon release reduced infraspinatus volume by 22% and increased fat content from 11% to 38%. These changes were not affected by repair. Fatty infiltration was associated with up-regulation of 227 lipid species, and increased levels of the adipocyte differentiation marker PPARG2 (peroxisome proliferator-activated receptor gamma 2). Nandrolone abrogated lipid accumulation, halved the loss in fiber area percentage, and up-regulated androgen receptor levels and transcript expression in the N22W but not the N6W group. The results document that nandrolone mitigates muscle-to-fat transformation after tendon release via a general down-regulation of lipid accumulation concomitantly with up-regulated expression of its nuclear receptor and downstream transcripts in skeletal muscle. Reduced responsiveness of retracted muscle to nandrolone as observed in the N6W group is reflected by a down-regulated transcript response.

2017-07-14 | MTBLS322 | MetaboLights

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