Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE192982 | GEO | 2022/01/26
REPOSITORIES: GEO
Similar Datasets
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.
2024-05-30 | GSE231848 | GEO
Project description:Objectives: To identify novel gene transcripts and biological processes in meniscus from patients with and without osteoarthritis (OA). Methods: We used microarrays to identify gene transcripts differentially expressed in meniscus tissues obtained from OA and non-OA patients (N=12 each). Real-time PCR was performed on selected gene transcripts. Biological processes and gene networking was examined computationally. Transcriptome signatures from OA and non-OA meniscus were mapped with 37 previously published gene transcripts differentially expressed between healthy and OA cartilage to evaluate how meniscus gene expression relates to cartilage with this disease. Results: We identified 168 gene transcripts that were significantly differentially expressed between OA (75 elevated, 93 repressed) and non-OA samples (≥1.5-fold). Among these, CSN1S1, COL10A1, WIF1, SPARCL1 and DEFA3 were the most prominent gene transcript elevated in OA meniscus and POSTN, VEGFA, CEMIP, COL6A3 and SOX11 were repressed in OA meniscus. Gene transcripts elevated in OA meniscus represented response to external stimuli, cell migration and localization while those repressed in OA meniscus represented histone deacetylase activity and skeletal development. Numerous long lncRNAs were differentially expressed between the two samples. When segregated by OA-associated gene transcripts, we observed three distinct clustering patterns of OA and non-OA meniscus. Conclusions: These data provide novel evidence for a role of epigenetically regulated histone deacetylation in meniscus tears as well as expression of lncRNAs. Patient clustering based on OA-associated gene transcripts confirmed that the meniscus in OA knees exhibited OA phenotype while injured meniscus demonstrated some signs towards OA.
2017-12-27 | GSE98918 | GEO
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.
2020-08-13 | GSE156132 | GEO
Project description:Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee, conditions that have promising applications in human meniscus tissue engineering. We hypothesized that “mechano-hypoxia conditioning,” using mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP), would enhance development of human meniscus fibrocartilage extracellular matrix in vitro. MFCs from inner human meniscus surgical discards were pre-cultured on porous type I collagen scaffolds with TGF-β3 supplementation to form baseline tissues with newly-formed matrix. They were then treated with DC or CHP under hypoxia (HYP, 3% O2) for 5 days. DC was the more effective load regime, and combined HYP/DC enhanced gene expression of fibrocartilage precursors. The individual treatments of DC and HYP regulated thousands of genes and combined in an overwhelmingly additive rather than synergistic manner. Baseline tissues were then treated with a short course of DC (5 vs 60 minutes, 10-20% vs 30-40% strain) with different pre-culture durations (3 vs 6 weeks). Longer courses of loading had diminishing returns in terms of gene regulation. There was a dose-effect for higher DC strains, whereas outcomes were mixed for different MFC donors in pre-culture durations. Finally, baseline tissues were conditioned for 3 weeks with mechano-hypoxia conditioning to assess mechanical and protein-level outcomes. There were 1.8 to 5.1-fold gains in the dynamic modulus relative to baseline in HYP/DC, but matrix outcomes were equal or inferior to static controls. Long-term mechano-hypoxia conditioning was effective in suppressing hypertrophic markers (e.g., COL10A1 10-fold suppression vs static/normoxia). Applied appropriately, mechano-hypoxia conditioning can support meniscus fibrocartilage development in vitro and may be useful as a strategy for developing non-hypertrophic articular cartilage using mesenchymal stem cells.
2021-08-23 | GSE180467 | GEO
Project description:Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro
| PRJNA794057 | ENA
Project description:The aim of this study is to demonstrate that mechanical unloading via SMG will induce a higher osteoarthritic-like gene profile in bioengineered meniscal cartilage from healthy female MFC versus healthy male MFC. This would serve as the molecular basis for early onset of knee osteoarthritis in females
2022-05-20 | GSE192983 | GEO
Project description:Osteoarthritis (OA) affects all tissues in the knee joint but therapeutic targets have often been selected for their role in cartilage damage and inflammation and largely omitted consideration of mechanisms that are mediating meniscus damage and more importantly there have been insufficient efforts to determine whether pathogenic processes are shared between tissues. Several scRNA-seq analyses have been performed in OA knees but have been largely restricted to the analysis of a single joint tissue of articular cartilage, or meniscus with the exception of one study that analyzed cartilage and synovium. Here, we performed scRNA-seq analyses of healthy and OA-affected human knee cartilage and menisci to interrogate separate and shared mechanisms in cellular homeostasis and OA pathogenesis.
2023-04-19 | GSE220243 | GEO
Project description:There is a need to clarify the role of the meniscus in knee OA which may be aided by the identification of biomarkers that reflect the molecular events involved in the tissue degradation. This is of particular importance in the early stages of the degenerative processes, a crucial phase when it might still be possible to interfere with disease progression before tearing and critical loss of meniscal function occurs. One way to achieve this goal is exploratory proteomics by mass spectrometry (MS), which has the potential to analyse the proteome of complex samples. Thus, our aim was to gain new knowledge about the molecular processes within the human meniscus by comparing the proteomic profiles of both the lateral and medial meniscus from healthy controls, subjects with mild signs of joint degeneration, and patients with end-stage knee OA, using a non-targeted MS approach operating in data-independent acquisition (DIA) mode. For the research purpose six groups were established: medial and lateral menisci from control donors (n=12), medial and lateral menisci from donors with mild signs of joint degeneration (n=13) and medial and lateral menisci from end-stage knee OA patients (n=12).
2024-04-03 | PXD042122 | Pride
Project description:Background: Osteoarthritis (OA) primarily affects mechanical load-bearing joints. The knee joint is the most impacted by OA. Knee OA (KOA) occurs in almost all demographic groups, but the prevalence and severity are disproportionately higher in females. The molecular mechanism underlying the pathogenesis and progression of KOA is unknown. The molecular basis of biological sex matters of KOA is not fully understood. Mechanical stimulation plays a vital role in modulating OA-related responses of load-bearing tissues. Mechanical unloading by simulated microgravity (SMG) induced OA-like gene expression in engineered cartilage, while mechanical loading by cyclic hydrostatic pressure (CHP), on the other hand, exerted a pro-chondrogenic effect. This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences. Methods: Tissue-engineered menisci were made from female and male meniscus fibrochondrocytes (MFCs) under static conditions of normal gravity in chondrogenic media and subjected to SMG and CHP culture. Constructs were assayed via histology, immunofluorescence, GAG/DNA assays, RNA sequencing, and testing of mechanical properties. Results: The mRNA expression of ACAN and COL2A1, was upregulated by CHP but downregulated by SMG. COL10A1, a marker for chondrocyte hypertrophy, was downregulated by CHP compared to SMG. Furthermore, CHP increased GAG/DNA levels and wet weight in both female and male donors, but only significantly in females. From the transcriptomics, CHP and SMG significantly modulated genes related to the ossification, regulation of ossification, extracellular matrix, and angiogenesis Gene Ontology (GO) terms. A clear difference in fold-change magnitude and direction was seen between the two treatments for many of the genes. Furthermore, differences in fold-change magnitudes were seen between male and female donors within each treatment. SMG and CHP also significantly modulated genes in OA-related KEGG pathways, such as mineral absorption, Wnt signalling pathway, and HIF-1 signalling pathway. Conclusion: Engineered menisci responded to CHP and SMG in a sex-dependent manner. SMG may induce an OA-like profile, while CHP promotes chondrogenesis. The combination of SMG and CHP could serve as a model to study the early molecular events of KOA and potential drug-targetable pathways.
| S-EPMC8904202 | biostudies-literature
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.
2015-03-06 | E-GEOD-66635 | biostudies-arrayexpress