Single Cell RNA Sequencing of Synovial Tissue in Adolescents Undergoing ACL Reconstruction
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ABSTRACT:
PROVIDER: PRJNA1179366 | ENA |
REPOSITORIES: ENA
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Project description:Background: Loss of motion and arthrofibrosis after anterior cruciate ligament reconstruction (ACLR) can be a devastating complication for athletes. The cellular and molecular pathogenesis of arthrofibrosis is poorly understood, limiting prevention and treatment options. Synovial inflammation may contribute to post-ACLR arthrofibrosis. Hypothesis/Purpose: We hypothesized that higher synovial immune cell infiltration and inflammatory/catabolic gene expression patterns at the time of ACLR would correlate with poorer motion-related outcomes. Study Design: Case Series Methods: Patients aged 10-18 undergoing primary ACLR were enrolled in a prospective pilot study, and synovial tissue biopsies were obtained during ACLR. Flow cytometry and single cell RNA-sequencing explored synovial cell types/frequencies and gene expression. Principle component analysis followed by clustering grouped patients into distinct immunophenotypes based on their synovial cell composition. Clinical follow-up with knee range of motion (ROM), need for lysis of adhesions, and patient reported outcome measures were collected and compared between immunophenotypes. Results: Enrolled patients (n = 17) underwent ACLR at a median of 37 days post-injury. Analysis revealed three distinct immunophenotypes. Type 1 comprised patients with the longest time between injury and surgery and the lowest hematopoietic and T cell infiltration. Types 2 and 3 had similar times between injury and surgery, and Type 2 had intermediate while Type 3 had the highest hematopoietic and T cell percentages. Type 3 was associated with worse ROM at 2- and 6-weeks post-op; T cell prevalence and ROM were inversely correlated at those time points. The only patient requiring lysis of adhesions for arthrofibrosis was in Type 3. Conclusion: Synovial immune infiltration after ACL injury shows variability between patients that clusters into three immunophenotypes correlating with early ROM and the risk of arthrofibrosis. T cell recruitment and infiltration was the strongest factor correlated with ROM outcomes and presents an exciting venue for future research on post-ACLR arthrofibrosis.
2024-11-10 | GSE280537 | GEO
Project description:In the current work, we used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. Our primary aim was to determine how the synovial fluid proteome differs between the two groups in an effort to identify candidate proteins that may be associated with the development of posttraumatic OA. We hypothesized that the development of macroscopic cartilage damage following surgical ACL transection would be accompanied by differential changes in synovial fluid proteome in untreated knees compared to repaired joints.
2019-02-16 | PXD012720 | Pride
Project description:Objective: To determine alterations in plasma miRNAs during early stages (2 weeks and 6 weeks) post ACL reconstruction surgery MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq550. MiRNA reads were then aligned with the mature miRNAs from miRBase v22.1 and human reference genome to create counts for each sample.
2024-07-26 | GSE253071 | GEO
Project description:Early MicroRNA and Metabolite Changes Post-ACL Reconstruction Surgery
| PRJNA1063752 | ENA
Project description:Analysis of gene expression profiles of ACL-MSCs derived from total knee arthroplasty (TKA) and ACL reconstruction patients. We hypothesized that the proportion of MSCs in ACL samples correlates negatively with donor age, i.e., the proportion of MSCs in ACL samples are higher in younger patients undergoing ACL reconstruction than in older patients undergoing TKA. Results provide additional information on the the effect of age on MSC properties, in particular, the differential regulation of genes encoding components of the extracellular matrix (ECM).
2014-12-01 | GSE59662 | GEO
Project description:The anterior cruciate ligament (ACL) is an essential stabilizer of the tibiofemoral articulation. ACL tears often lead to functional instability and are associated with an increased risk for osteoarthritis. The healing potential of the injured ACL is poorly understood and is considered to be limited. Transcriptome-wide expression profiles of 24 human ACL remnants recovered at the time of surgical reconstruction were analyzed utilizing the Agilent human 8x60K microarray platform. Gene ontology was performed on differentially expressed transcripts based on time-from-injury (acute, <3 months; intermediate, 3-12 months; chronic, >12 months). A subset of transcripts was validated via microfluidic digital polymerase-chain-reaction. Expression of periostin, a highly differentially expressed transcript, was tested by immunohistochemistry. Numerous transcripts covering important functional classifications were differentially expressed by time-from-injury. In acute tears, processes representing angiogenesis were repressed while those representing stem-cell differentiation were elevated. In intermediate tears, processes representing stem-cell proliferation concomitant with cellular component organization/cellular localization were elevated. In chronic tears, processes denoting myosin filament organization were elevated while those representing cellular component organization/cell localization and extracellular matrix organization were repressed. Expression levels of periostin were down-regulated in chronic tears compared to acute (42-fold) and intermediate (29-fold) tears. Immunohistochemistry confirmed a decline in periostin expression in tissues from chronic tears. These findings suggest an initial attempt of the injured ACL to repair, which declines with time-from-injury. These findings have implications for efforts to repair the ACL and may be relevant for reconstruction of the ACL. The functional role of periostin in ACL injuries, and the potential implication for surgical treatment, warrants further investigation. Total RNA obtained frominjured anterior cruciate ligament (ACL) tissues from pateints undergoing ACL surgery.
2014-09-13 | E-GEOD-61385 | biostudies-arrayexpress
Project description:Patients with anterior cruciate ligament (ACL) tears have a significantly increased risk for developing knee osteoarthritis. These injuries often result in a knee effusion in response to the injury. Early changes in these effusions could be informative regarding initial steps in the development of post traumatic osteoarthritis. The purpose of this study was to test the hypothesis that the proteomics of knee synovial fluid changes over time following ACL injury.
2022-06-23 | MSV000089716 | MassIVE
Project description:The genomic landscape of hepatic tissue affected by nonalcoholic steatohepatitis (NASH) in severely obese adolescents undergoing bariatric surgery is unknown. Our purpose here was to uncover genomic profiles of obese controls, and obese cases with nonalcoholic fatty liver disease (NAFLD), borderline nonalcoholic steatohepatitis, and definite nonalcoholic steatohepatitis, in order to clarify molecular functions, biological processes, and pathways that are dysregulated in nonalcoholic steatohepatitis in the severely obese adolescent. In a prospective observational cohort study, we have intra-operatively obtained 165 liver samples; of these 67 were submited for microarray analysis. Through ANOVA, we found 8648 genes with differential regulation between the four histologies; from these, we uncovered gene signatures shared between borderline and definite nonalcoholic steatohepatitis, and gene sets with differential effects between borderline and definite.
2017-07-21 | GSE66676 | GEO
Project description:In 21 patients undergoing revision arthroplasty due to septic or aseptic implant loosening, synovial fluid was collected intraoperatively after opening the joint capsule. In a proteomic MS approach, we wanted now to investigate these synovial fluids for novel proteogenic markers of periprosthetic infections.
2024-05-21 | PXD047507 | Pride
Project description:Human growth plate chondrocytes were isolated from the distal femoral growth plate from 3 different adolescents undergoing epiphysiodesis. Cell were isolated and grown in monolayers, long term, in 20% serum. Cells were replated and cultured 48 h in 0.5% serum.
2008-06-12 | E-GEOD-1278 | biostudies-arrayexpress