Transcriptome Analysis of Human Injured Meniscus Reveals a Distinct Phenotype of Meniscus Degeneration with Aging
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ABSTRACT: In this study, we have tested the variation in gene expression signatures in human injured meniscus with age and degree of chondrosis in the knee. We found several genes that were differentially regulated with each of these factors and they represent important biological pathways in osteoarthritis research. Total RNA obtained from isolated injured meniscus tissues from patients undergoing arthroscopic partial meniscectomy.
Project description:In this study, we have tested the variation in gene expression signatures in human injured meniscus with age and degree of chondrosis in the knee. We found several genes that were differentially regulated with each of these factors and they represent important biological pathways in osteoarthritis research.
Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.
Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage.
Project description:mRNA expression levels in synovial fibroblasts in 6 rheumatoid arthritis patients versus 6 osteoarthritis patients. Experiment Overall Design: Synovial tissue was obtained from open joint replacement surgery or Experiment Overall Design: arthroscopic synovectomy. Patients with RA or OA (n = 6 each for gene expression analysis and further patients for validation experiments) were classified according to the ACR criteria.
Project description:Muscle Stem Cells or satellite cells (SCs) are required for muscle regeneration. In resting muscles, SCs are kept in quiescence. After injury, SCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. The transcriptome alteration during SC activation is well characterized. While transcriptome is not exactly represent proteome because of post-transcriptional regulations such as miRNA induced gene silencing. However, little is known about SC proteome. We obtained in vivo activated SCs (ASCs) from 3 days post injured muscles for high resolution mass spectrometry Bruker timsTOF Pro. Compared with QSC proteome,, we identified the pathways that are differentially expressed between them.
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.
Project description:This study aims to establish an osteoarthritis (OA)-like phenotype in human meniscus models under SMG conditions and assess whether sex-dependent expression patterns indicative of knee OA (KOA) are present under short-term SMG. Cell cultures were maintained on human matrix coated surface to maintain original phenotype.
Project description:Osteoarthritis is characterized by degeneration of cartilage and bone in the synovial joints. Recent findings suggest that inflammation may play a role in osteoarthritis, with synovitis being associated with the clinical symptoms of osteoarthritis. Furthermore, we have found that levels of inflammatory complement components are abnormally high in the synovial fluid of individuals with osteoarthritis. To determine whether synovial membranes could be a source of complement and other inflammatory molecules in osteoarthritic joints, we characterized the expression of genes in synovial membranes from patients with early-stage or end-stage osteoarthritis. Samples of synovial membrane were obtained from the suprapatellar pouch of patients with osteoarthritis who were treated at the Hospital for Special Surgery. Specifically, samples were from 10 patients with early-stage knee osteoarthritis who were undergoing arthroscopic procedures for degenerative meniscal tears (with documented cartilage degeneration but no full-thickness cartilage loss, Kellgren Lawrence score </=2), and from 9 patients with end-stage knee osteoarthritis ( diffuse full thickness cartilage erosion) who were undergoing total knee joint replacement. Raw data from microarray analysis of healthy synovial membranes, which were run on the same platform and array as our osteoarthritic samples, were downloaded from the NCBI Gene Expression Omnibus (accession number GSE12021) and used for comparison. The 19 new Samples of this Series were analyzed (RMA) together with 7 previously submitted healthy individual Samples (GSM175810, GSM175812, GSM176290, GSM176291, GSM176292, GSM176268, GSM176269). The complete RMA data are provided as a supplementary file on the Series record. The GSE12021 reanalyzed data are also provided as a supplementary file on the Series record. GSE32317_12genes.txt includes data from figure 1 of the paper.
Project description:Meniscus degeneration is one of the manifestations of knee osteoarthritis, but its specific molecular mechanism is still not very clear. We used Wuzhishan pig's anterior cruciate ligament resection to prepare meniscus degeneration models, and applied gene chip technology to detect the expression of differential genes in the degenerated meniscus tissue. The study detected a total of 893 differentially expressed genes, mainly related to hormones, apoptosis, inflammation and other mechanisms, and analyzed that TRP channels may play a key role. All in all, we have established a reliable animal model of meniscus degeneration and found that meniscus degeneration involves several possible molecular mechanisms, which provide molecular targets for future treatment of the disease.
Project description:Gene expression of macrophages from injured muscles of bDCRE mutant mice was compared with that of Cebpb wt mice. Skeletal muscles were injured by cardiotoxin injection and infiltrating macrophages were isolated 6 days post-injury by FACS sorting of Mac-1+F4/80+ cells. 4 biological replicates were generated for each genotype and expression profiles were determined by hybridization to Affymetrix Moe430_2 arrays.