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The transient chondrocyte phenotype in osteophytic cartilage - a role of PEDF?

ABSTRACT: Pigment Epithelium-Derived Factor (PEDF) has recently been identified as a factor that is significantly upregulated in late-stage osteoarthritic cartilage in which chondrocytes are confronted with terminal differentiation and cell death. Since PEDF is known to induce cell death of endothelial cells, it may also be responsible for terminal differentiation and cell death in cartilage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE43923 | GEO | 2013/01/31

SECONDARY ACCESSION(S): PRJNA188168

REPOSITORIES: GEO

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The transient chondrocyte phenotype in osteophytic cartilage - a role of PEDF?

Project description:Pigment Epithelium-Derived Factor (PEDF) has recently been identified as a factor that is significantly upregulated in late-stage osteoarthritic cartilage in which chondrocytes are confronted with terminal differentiation and cell death. Since PEDF is known to induce cell death of endothelial cells, it may also be responsible for terminal differentiation and cell death in cartilage. Using cDNA microarray analysis, we found PEDF among the factors with the strongest differential expression and significant higher levels (118.5-fold) in osteophytic cartilage compared with articular cartilage. This study explored if PEDF interferes with the stable chondrocyte phenotype by promoting terminal differentiation or cell death.

2013-01-31 | E-GEOD-43923 | biostudies-arrayexpress

Transcriptional profile of human macrophages stimulated by cartilage fragments

Project description:Accumulating evidence suggests that synovitis is associated with osteoarthritic process. Macrophages are predominant cell type in synovium and play principal role in development of synovitis. Our earlier study suggests that the interaction between cartilage fragments and macrophages exacerbates osteoarthritic process. However, molecular mechanisms by which cartilage fragments trigger cellular responses remain to be investigated. Therefore, the current study aims at analyzing molecular response of macrophages to cartilage fragments by RNA-seq

2020-05-13 | GSE141308 | GEO

Differential expression analysis of human small RNAs in young normal, old normal (protected)) and old osteoarthritis (unprotected ) knee cartilage

Project description:Human cartilage taken from young normal knees following anterior cruciate ligament repair and osteoarthritic cartilage; old normal (protected) and old osteoarthritic (unprotected) following total knee arthroplasty. Total RNA extracted using mirVana miRNA isolation kit (Life Technologies). The Affymetrix Flash Tag labelling kit was used to prepare samples for hybridisation onto Affymetrix miRNA 4.0 arrays.

2017-12-31 | E-MTAB-5716 | biostudies-arrayexpress

Genome-wide DNA methylation study of hip and knee osteoarthritic and healthy cartilage reveals embryonic organ and skeletal system morphogenesis as major pathways involved in osteoarthritis

Project description:Cartilage samples were collected from hip or knee joint replacement patients either due to primary OA or hip fractures as controls. DNA was extracted from the collected cartilage and assayed by Illumina Infinium HumanMethylation450 âBeadChip array, which allows for the analysis of >480,000 CpG sites. Bisulphite converted DNA from 5 hip osteoarthritic, 6 knee osteoarthritic and 7 hip healhty cartilage samples were hybridised to the Illumina Infinium HumanMethylation450 âBeadChip array

2016-07-01 | E-GEOD-73626 | biostudies-arrayexpress

Differential expression analysis of small RNAs in young normal and old osteoarthritis cartilage

Project description:Human cartilage taken from young normal knees following anterior cruciate ligament repair and osteoarthritic cartilage following total knee arthroplasty. Total RNA extracted using mirVana miRNA isolation kit (Life Technologies). The Affymetrix Flash Tag labelling kit was used to prepare samples for hybridisation onto Affymetrix miRNA 4.0 arrays.

2017-12-31 | E-MTAB-5715 | biostudies-arrayexpress

Whole transcriptomic analysis of mouse ATDC5 chondrocyte precursor cells under 25 MPa hydrostatic pressure for 0, 1 , 4 or 24h

Project description:Hydrostatic pressure is one of the main mechanical stimuli cartilage cells are submitted to during joint loading. If moderate hydrostatic pressure is known to be beneficial to cartilage differentiation, excessive pressure, on the other hand, induces changes in cartilage similar to those observed in osteoarthritic cartilage. Therefore, the purpose of the experiment is to identify new target genes of high hydrostatic pressure in chondrocyte precursor cells.

2017-12-02 | E-MTAB-5326 | biostudies-arrayexpress

Comparison of Transient + articular cartilage (TC+AC) over pure transient cartilage (TC) from both E12 and E14 chicken tibia

Project description:During the past two decades although many genes e.g.,Gdf5, Wnt9a, Noggin etc. have been identified and characterized in joint development, still a comprehensive understanding of molecular network operational in articular cartilage morphogenesis is far from being drawn. This might be due to incompleteness in the number of molecules identified. We used microarray profiling to identify chicken articular cartilage specific genes. We decided to conduct microarray-based transcriptome comparison of HH38 (E12) and HH40 (E14). As it is difficult to clearly dissect out articular cartilage even at these late stages we decided to identify the transcripts that are enriched in the transient + articular cartilage (TC+AC) over pure transient cartilage (TC) thus using TC as control or reference samples

2016-06-09 | GSE69684 | GEO

PEDF Is Associated with the Termination of Chondrocyte Phenotype and Catabolism of Cartilage Tissue.

Project description:Objective. To investigate the expression and target genes of pigment epithelium-derived factor (PEDF) in cartilage and chondrocytes, respectively. Methods. We analyzed the expression pattern of PEDF in different human cartilaginous tissues including articular cartilage, osteophytic cartilage, and fetal epiphyseal and growth plate cartilage, by immunohistochemistry and quantitative real-time (qRT) PCR. Transcriptome analysis after stimulation of human articular chondrocytes with rhPEDF was performed by RNA sequencing (RNA-Seq) and confirmed by qRT-PCR. Results. Immunohistochemically, PEDF could be detected in transient cartilaginous tissue that is prone to undergo endochondral ossification, including epiphyseal cartilage, growth plate cartilage, and osteophytic cartilage. In contrast, PEDF was hardly detected in healthy articular cartilage and in the superficial zone of epiphyses, regions that are characterized by a permanent stable chondrocyte phenotype. RNA-Seq analysis and qRT-PCR demonstrated that rhPEDF significantly induced the expression of a number of matrix-degrading factors including SAA1, MMP1, MMP3, and MMP13. Simultaneously, a number of cartilage-specific genes including COL2A1, COL9A2, COMP, and LECT were among the most significantly downregulated genes. Conclusions. PEDF represents a marker for transient cartilage during all neonatal and postnatal developmental stages and promotes the termination of cartilage tissue by upregulation of matrix-degrading factors and downregulation of cartilage-specific genes. These data provide the basis for novel strategies to stabilize the phenotype of articular cartilage and prevent its degradation.

| S-EPMC5278211 | biostudies-literature

Gut-liver axis calibrates intestinal stem cell fitness via PEDF

Project description:The gut and liver are recognized to mutually communicate through the biliary tract, portal vein and systemic circulation, but it remains unclear how this gut-liver axis regulates intestinal physiology. Through hepatectomy, transcriptomic and proteomic profiling, we identified pigment epithelium-derived factor (PEDF), a liver-derived soluble Wnt inhibitor, that restrains intestinal stem cell (ISC) hyperproliferation to maintain gut homeostasis by suppressing the Wnt/b-catenin signaling pathway. Further, we found that microbial danger signals occurring as a result of intestinal inflammation can be sensed by the liver to repress PEDF production via peroxisome proliferator-activated receptor-a (PPARa), liberating ISC proliferation to accelerate tissue repair in the gut. Finally, treatment of mice with fenofibrate, a clinical agent of PPARa agonist for hypolipidemia enhances the susceptibility of colitis via PEDF activity. Therefore, we have identified a distinct role for PEDF in calibrating ISC expansion for intestinal homeostasis via reciprocal interactions between the gut and liver.

2024-01-16 | GSE228829 | GEO

Compensatory growth and recovery of tissue cytoarchitecture after transient cartilage-specific cell death in foetal mouse limbs

Project description:A major question in developmental and regenerative biology is how organ size is controlled by progenitor cells. For example, while limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse foetal cartilage was repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states was delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death was over, chondroprogenitor differentiation was accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlated with, and was necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

2024-03-11 | GSE235779 | GEO

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