Transcription profiling by array of Kashin-beck disease and osteoarthritis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
DISEASE(S): primary osteoarthritis
SUBMITTER: Feng Zhang
PROVIDER: E-MEXP-3474 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Large scale RNA-Seq analysis was performed to investigate the transcriptomic response to osteoarthritis in cartilage and investigate potential subgroups of patients. Data were collected from intact knee cartilage (posterior lateral condyle) from at total of 60 patients with osteoarthritis (OA) following total knee replacement and 10 control non-OA patients following amputation.
2017-12-13 | E-MTAB-6266 | biostudies-arrayexpress
Project description:Objective. Identify novel genes and pathways specific to superficial (SZ), middle (MZ) and deep zones (DZ) of normal articular cartilage. Methods. Articular cartilage was obtained from knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. Data obtained with human tissue were compared to bovine cartilage zone specific DNA arrays. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. Results. The greatest differences were observed between SZ and DZ in both human and bovine cartilage. The MZ was transitional between the SZ and DZ and thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biological processes enriched in the SZ relative to the DZ, include most prominently ECM receptor interactions, cell adhesion molecules, regulation of actin cytoskeleton, ribosome-related functions and signaling aspects such as Interferon gamma, IL4, CDC42Rac and Jak-Stat. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR_SMRTE. Conclusion. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations. 12 samples, 4 donors, 3 conditions each donor (SZ, MZ and DZ), 0 donor replicates, comparisons made between SZ, MZ and DZ to identify differentially expressed genes.
2012-07-31 | E-GEOD-39795 | biostudies-arrayexpress
Project description:Articular cartilage is deprived of blood vessels and nerves, and the only cells residing in this tissue are chondrocytes. The molecular properties of the articular cartilage and the architecture of the extracellular matrix demonstrate a complex structure that differentiates on the depth of tissue. Osteoarthritis (OA) is a degenerative joint disease, the most common form of arthritis, affecting the whole joint. It is associated with ageing and affects the joints that have been continually stressed throughout life including the knees, hips, fingers, and lower spine region. OA is a multifactorial condition of joint characterised by articular cartilage loss, subchondral bone sclerosis, and inflammation leading to progressive joint degradation, structural alterations, loss of mobility and pain. Articular cartilage biology is well studied with a focus on musculoskeletal diseases and cartilage development. However, there are relatively few studies focusing on zonal changes in the cartilage during osteoarthritis.
2022-05-19 | PXD029116 | Pride
Project description:Successfully replacing damaged cartilage with tissue-engineered constructs requires integration with the host tissue and could benefit from leveraging the native tissue's intrinsic healing capacity; however, efforts are limited by a poor understanding of how cartilage repairs minor defects. Here, we investigated the conditions that foster natural cartilage tissue repair to identify strategies that might be exploited to enhance the integration of engineered/ grafted cartilage with host tissue. We damaged porcine articular cartilage explants and using a combination of pulsed SILAC-based proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies reveal that integration of damaged cartilage surfaces is not driven by neo-matrix synthesis, but rather local depletion of proteoglycans. ADAMTS4 expression and activity are upregulated in injured cartilage explants, but integration could be reduced by inhibiting metalloproteinase activity with TIMP3. These observations suggest that catabolic enzyme-mediated proteoglycan depletion likely allows existing collagen fibrils to undergo cross-linking, fibrillogenesis, or entanglement, driving integration. Catabolic enzymes are often considered pathophysiological markers of osteoarthritis. Our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions and in osteoarthritis, but could also be harnessed in tissue engineering strategies to mediate repair. Statement of significance: Cartilage tissue engineering strategies require graft integration with the surrounding tissue; however, how the native tissue repairs minor injuries is poorly understood. We applied pulsed SILACbased proteomics, ultrastructural imaging, and catabolic enzyme blocking strategies to a porcine cartilage explant model and found that integration of damaged cartilage surfaces is driven by catabolic enzyme-mediated local depletion of proteoglycans. Although catabolic enzymes have been implicated in cartilage destruction in osteoarthritis, our findings suggest that damage-induced upregulation of metalloproteinase activity may be a part of a healing response that tips towards tissue destruction under pathological conditions. They also suggest that this natural cartilage tissue repair process could be harnessed in tissue engineering strategies to enhance the integration of engineered cartilage with host tissue.
2022-07-18 | PXD035246 | Pride
Project description:This experiment captures the expression of genes between two sites of human cartilage within the same patients to allow investigation of genomic responses to damage during osteoarthritis. Eight patients with symptomatic OA undergoing total knee replacement (n=8, age range 65-79 years, mean age 70.3) were used in this study. Cartilage from paired osteochondral samples were isolated from the intact PLC (posterior lateral condyle) and the damaged DMC (distal medial condyle) for RNA-seq analysis.
2016-04-06 | E-MTAB-4304 | biostudies-arrayexpress
Project description:Osteoarthritis (OA) is a complex degenerative joint disease, which is not only a cartilage but also a bone disease. A better understanding of the early molecular mechanism changes of subchondral bone in vivo may contribute to elucidating the pathogenesis of OA. We used microarray technology to investigate the time-course molecular changes of subchondral bone just beneath damaged cartilage in early stage of experimental osteoarthritis, and found 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks postsurgery.Further analysis of dysregulated genes indicated that subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some known dysregulated genes suspected roles in influencing bone development or bone remodeling, such as Alp, Igf1, Tgf M-NM-21, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh, were confirmed by real-time PCR, and results indicated that our microarray data could accurately reflect gene expression patterns of early OA. Subsequently, to validate the results of our microarray analysis at protein level, immunohistochemistry staining was introduced to investigate the translational level of genes Mmp3 and Aspn in tissue sections, and results showed that the level of Mmp3 protein expression was totally matched the results of microarray and real-time PCR analysis. Nevertheless, the expression of Aspn protein was not observed differentially expressed at any time point. Ninety 10-week-old male Sprague-Dawley rats, weighing 300-325g, were used in the study. Animals were equally divided into two groups: experimental group (E-Group) and sham-operated group (S-Group). The E-Group rats underwent open surgery, involved in both medial meniscectomy and medial collateral ligament (MCL) transaction with micro-scissors. The S-Group rats were carried out with a sham operation, via a similar incision, without operations of the medial meniscus and the medial collateral ligament.Animals were killed at 1, 2, and 4 weeks postsurgery, and 15 animals were put into use per-timepoint in each treatment group. 5 animals were used for histological analysis and immunohistochemistry, and others were used for microarray study and Real-time polymerase chain reaction (PCR) analysis equally at each timepoint.
2012-12-11 | E-GEOD-30322 | biostudies-arrayexpress
Project description:Osteoarthritis (OA) is a chronic disease of the joint characterized by a progressive degradation of articular cartilage and subchondral bone. In healthy tissue, specialized cells called chondrocytes are regulating a balanced cartilage catabolism and anabolism. By contrast osteoarthritic joints are characterized by a dramatic increase of cartilage catabolism, due to changes of gene expression patterns within chondrocytes. To identify potential epigenetic differences regulating this process a genome-wide methylation screening of paired unaffected and osteoarthritic knee cartilage samples was performed. Therefore samples of macroscopic arthritic and non-arthritic cartilage areas of the femoral condyle of five female patients were collected and DNA isolation was performed. For being able to investigate methylation changes on a genome-wide scale using only limited amounts of DNA a specific amplification protocol for mainly methylated DNA has been established, based on combinations of different methylation-sensitive and M-bM-^@M-^Sindependent restriction digestions. The amplified DNA was then labeled and hybridized onto Agilent M-bM-^@M-^\Human Promoter Whole GenomeM-bM-^@M-^] microarrays. A random variance t-test for paired (per patient) samples was performed, identifying 1214 differentially methylated genetic targets between arthritic and non-arthritic samples. The biological relevance of these genes was then further investigated via Gene Ontology (GO) and KEGG pathway analysis. DNA isolated of paired arthritic and non-arthritic knee cartilage samples of five different female osteoarthritis patients (10 samples) was methylation-specifically amplified using combinations of methylation-sensitive and -insensitive restriction enzymes. Amplicons were dye labeled (Cy3) and hybridized onto 2x244k Agilent Human Promoter microarrays.
2014-07-01 | E-GEOD-48422 | biostudies-arrayexpress
Project description:The purpose of this study was to characterize the histologic development of OA in a mouse model where OA is induced by destabilization of the medial meniscus (DMM model) and to identify genes regulated during different stages of the disease, using RNA isolated from the joint M-bM-^@M-^\organM-bM-^@M-^] and analyzed using microarrays.427 genes from the microarrays passed consistency and significance filters. There was an initial up-regulation at 2 and 4 weeks of genes involved in morphogenesis, differentiation, and development, including growth factor and matrix genes, as well as transcription factors including Atf2, Creb3l1, and Erg. Most genes were off or down-regulated at 8 weeks with the most highly down-regulated genes involved in cell division and the cytoskeleton. Gene expression increased at 16 weeks, in particular extracellular matrix genes including Prelp, Col3a1 and fibromodulin.The results support a phasic development of OA with early matrix remodelling and transcriptional activity followed by a more quiescent period that is not maintained. A group of 9 mice was used for collection of RNA at time 0 (before surgery) when the animals were 12 weeks old. For the other time points, 9 DMM and 9 sham controls were sacrificed at 2, 4, 8, and 16 weeks after surgery for RNA isolation. The tissue included tibial plateau and femoral condyle articular cartilage, subchondral bone with any osteophytes, meniscus, and the joint capsule with synovium was used for RNA isolation. The tissue was treated with RNAlaterM-BM-. (Invitrogen) prior to freezing and storage at -800 C. RNA was extracted by homogenization using the Precellys 24 tissue homogenizer (Bertin Technologies purchased from MO BIO) and the amount and quality of the RNA was determined using an Agilent 2100 Bioanalyzer. RNA was pooled prior to microarray analysis such that 3 randomly selected samples from each surgical group and time point were pooled to create each biological replicate. Because 9 mice were used for each experimental group, a total of three biological replicates per group were analyzed using the Affymetrix Mouse Genome 430 2.0 oligonucleotide arrays as described. One replicate pool, which was from week two DMM mice, did not meet the RNA integrity level needed for microarray analysis; thus, this pool was not analyzed further, leaving two pools for the week two DMM mice.
2012-11-01 | E-GEOD-41342 | biostudies-arrayexpress
Project description:Objective. Identify novel genes and pathways specific to superficial (SZ), middle (MZ) and deep zones (DZ) of normal articular cartilage. Methods. Articular cartilage was obtained from knees of 4 normal human donors. The cartilage zones were dissected on a microtome. RNA was analyzed on human genome arrays. Data obtained with human tissue were compared to bovine cartilage zone specific DNA arrays. Genes differentially expressed between zones were evaluated using direct annotation for structural or functional features, and by enrichment analysis for integrated pathways or functions. Results. The greatest differences were observed between SZ and DZ in both human and bovine cartilage. The MZ was transitional between the SZ and DZ and thereby shared some of the same pathways as well as structural/functional features of the adjacent zones. Cellular functions and biological processes enriched in the SZ relative to the DZ, include most prominently ECM receptor interactions, cell adhesion molecules, regulation of actin cytoskeleton, ribosome-related functions and signaling aspects such as Interferon gamma, IL4, CDC42Rac and Jak-Stat. Two pathways were enriched in the DZ relative to the SZ, including PPARG and EGFR_SMRTE. Conclusion. These differences in cartilage zonal gene expression identify new markers and pathways that govern the unique differentiation status of chondrocyte subpopulations. 6 samples, 2 bovine donors, 3 conditions each donor (SZ, MZ and DZ), 0 donor replicates, comparisons made between SZ, MZ and DZ to identify differentially expressed genes.
2012-07-31 | E-GEOD-39796 | biostudies-arrayexpress
Project description:In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared to healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.
2020-01-27 | PXD012879 | Pride