FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2226061304> ?p ?o ?g. }

• W2226061304 endingPage "386" @default.
• W2226061304 startingPage "385" @default.
• W2226061304 abstract "Clonal chondrocytes of osteoarthritic (OA) cartilage express an aberrant set of genes. We hypothesize that this aberrant gene expression may be due to clonally inherited epigenetic changes, defined as altered gene expression without changes in genetic sequence. The major epigenetic changes are due to altered DNA methylations in crucial parts of the promoter region. If the cytosines of CpG dinucleotides are methylated, the gene will be silenced, even if the right transcription factors are present. Similarly, de-methylations may activate previously silenced genes. Our aims were to provide ‘proof-of-concept’ data by examining the methylation status of genes in OA vs non-OA chondrocytes. Articular cartilage was obtained a) from the cartilage of fracture-neck-of-femur (#NOF) patients and b) from or around the eroded regions of OA samples. The former was full thickness cartilage, the latter was partially degraded cartilage, which contained mostly clonal chondrocytes as confirmed by histology. The cartilage samples were ground in a freezer mill (Glen Creston, UK) and DNA was extracted with a Qiagen DNeasy maxi kit. To assess DNA methylation status, the genomic DNA was treated overnight with methylation-sensitive restriction enzymes. Cleavage of selected sites was detected by PCR amplifications with primer pairs designed to bracket selected promoter regions. Loss of the PCR band after digestion with the enzymes indicated absence of methylations, whereas presence of the band indicated methylated cytosine. We selected MMP-9 as one of genes that is activated in OA. Transcription of mmp-9 is regulated by a 670 bp sequence at the 5′-end flanking region, which contains 6 CpGs and a further 21 CpGs within the 1.5 kb region further upstream. A PCR primer pair was designed to bracket a 350bp sequence upstream from the transcription start site of mmp-9, which contained four of the six potential methylation sites, cleaved by the methylation-sensitive enzymes AciI and HhaI. DNA from 9 OA patients, 5 #NOF patients and 1 rheumatoid arthritic (RA) patient were digested with HhaI or AciI and examined for the presence or absence of PCR bands. In all patients, digestion with HhaI abolished the PCR band, indicating that the HhaI site was never methylated in either #NOF or OA patients. However, a remarkable difference was found after digestion with AciI: in 8/9 OA patients, the PCR band was no longer detectable, while in 4/5 #NOF patients the PCR band was still present. This suggested that all three AciI cleavage sites were methylated in the majority of chondrocytes from #NOF patients, while at least one of the three AciI cleavage sites was unmethylated in OA patients. Interestingly, the PCR band was present in the RA patient, suggesting methylation of the AciI cleavage sites. The present study provides the first ‘proof-of-concept’ data that suggest epigenetic changes may play a role in the etiology of osteoarthritis. Clearly further work is required to establish the generality of the present findings and whether de-methylations are also found in the promoter regions of other genes that are aberrantly expressed in OA." @default.
• W2226061304 created "2016-06-24" @default.
• W2226061304 creator A5022107112 @default.
• W2226061304 creator A5023108722 @default.
• W2226061304 creator A5030767940 @default.
• W2226061304 creator A5045206303 @default.
• W2226061304 creator A5064330571 @default.
• W2226061304 date "2006-10-01" @default.
• W2226061304 modified "2023-09-27" @default.
• W2226061304 title "CAN EPIGENETIC CHANGES IN DNA METHYLATIONS EXPLAIN THE ALTERED GENE EXPRESSION IN OSTEOARTHRITIS" @default.
• W2226061304 hasPublicationYear "2006" @default.
• W2226061304 type Work @default.
• W2226061304 sameAs 2226061304 @default.
• W2226061304 citedByCount "0" @default.
• W2226061304 crossrefType "journal-article" @default.
• W2226061304 hasAuthorship W2226061304A5022107112 @default.
• W2226061304 hasAuthorship W2226061304A5023108722 @default.
• W2226061304 hasAuthorship W2226061304A5030767940 @default.
• W2226061304 hasAuthorship W2226061304A5045206303 @default.
• W2226061304 hasAuthorship W2226061304A5064330571 @default.
• W2226061304 hasConcept C101762097 @default.
• W2226061304 hasConcept C104317684 @default.
• W2226061304 hasConcept C105702510 @default.
• W2226061304 hasConcept C116114238 @default.
• W2226061304 hasConcept C128319531 @default.
• W2226061304 hasConcept C140173407 @default.
• W2226061304 hasConcept C150194340 @default.
• W2226061304 hasConcept C153911025 @default.
• W2226061304 hasConcept C190727270 @default.
• W2226061304 hasConcept C2780550940 @default.
• W2226061304 hasConcept C33288867 @default.
• W2226061304 hasConcept C37080517 @default.
• W2226061304 hasConcept C41091548 @default.
• W2226061304 hasConcept C54355233 @default.
• W2226061304 hasConcept C552990157 @default.
• W2226061304 hasConcept C86803240 @default.
• W2226061304 hasConceptScore W2226061304C101762097 @default.
• W2226061304 hasConceptScore W2226061304C104317684 @default.
• W2226061304 hasConceptScore W2226061304C105702510 @default.
• W2226061304 hasConceptScore W2226061304C116114238 @default.
• W2226061304 hasConceptScore W2226061304C128319531 @default.
• W2226061304 hasConceptScore W2226061304C140173407 @default.
• W2226061304 hasConceptScore W2226061304C150194340 @default.
• W2226061304 hasConceptScore W2226061304C153911025 @default.
• W2226061304 hasConceptScore W2226061304C190727270 @default.
• W2226061304 hasConceptScore W2226061304C2780550940 @default.
• W2226061304 hasConceptScore W2226061304C33288867 @default.
• W2226061304 hasConceptScore W2226061304C37080517 @default.
• W2226061304 hasConceptScore W2226061304C41091548 @default.
• W2226061304 hasConceptScore W2226061304C54355233 @default.
• W2226061304 hasConceptScore W2226061304C552990157 @default.
• W2226061304 hasConceptScore W2226061304C86803240 @default.
• W2226061304 hasLocation W22260613041 @default.
• W2226061304 hasOpenAccess W2226061304 @default.
• W2226061304 hasPrimaryLocation W22260613041 @default.
• W2226061304 hasRelatedWork W1795358129 @default.
• W2226061304 hasRelatedWork W1870847067 @default.
• W2226061304 hasRelatedWork W1917637636 @default.
• W2226061304 hasRelatedWork W193699753 @default.
• W2226061304 hasRelatedWork W1968542395 @default.
• W2226061304 hasRelatedWork W1993442685 @default.
• W2226061304 hasRelatedWork W2071225459 @default.
• W2226061304 hasRelatedWork W2088911740 @default.
• W2226061304 hasRelatedWork W2093922073 @default.
• W2226061304 hasRelatedWork W2314978987 @default.
• W2226061304 hasRelatedWork W2375876315 @default.
• W2226061304 hasRelatedWork W2398241271 @default.
• W2226061304 hasRelatedWork W2547169284 @default.
• W2226061304 hasRelatedWork W2560779806 @default.
• W2226061304 hasRelatedWork W2590516380 @default.
• W2226061304 hasRelatedWork W2613855915 @default.
• W2226061304 hasRelatedWork W2807462236 @default.
• W2226061304 hasRelatedWork W282829863 @default.
• W2226061304 hasRelatedWork W3012235517 @default.
• W2226061304 hasRelatedWork W3138527795 @default.
• W2226061304 isParatext "false" @default.
• W2226061304 isRetracted "false" @default.
• W2226061304 magId "2226061304" @default.
• W2226061304 workType "article" @default.