Objective. To perform a genome-wide DNA methylation study to identify DNA methylation changes in osteoarthritic (OA) cartilage tissue.Methods. The contribution of differentially methylated genes to OA pathogenesis was assessed by bioinformatic analysis, gene expression analysis, and histopathologic severity correlation. Genome-wide DNA methylation profiling of >485,000 methylation sites was performed on eroded and intact cartilage from within the same joint of 24 patients undergoing hip arthroplasty for OA. Genes with differentially methylated CpG sites were analyzed to identify overrepresented gene ontologies, pathways, and upstream regulators. The messenger RNA expression of a subset of differentially methylated genes was analyzed by reverse transcription-polymerase chain reaction. Histopathology was graded by modified Mankin score and correlated with DNA methylation.Results. We identified 550 differentially methylated sites in OA. Most (69%) were hypomethylated and enriched among gene enhancers. We found differential methylation in genes with prior links to OA, including RUNX1, RUNX2, DLX5, FURIN, HTRA1, FGFR2, NFATC1, SNCAIP, and COL11A2. Among these, RUNX1, HTRA1, FGFR2, and COL11A2 were also differentially expressed. Furthermore, we found differential methylation in approximately one-third of known OA susceptibility genes. Among differentially methylated genes, upstream regulator analysis showed enrichment of TGFB1 (P ‫؍‬ 4.40 ؋ 10 ؊5 ) and several microRNAs including miR-128 (P ‫؍‬ 4.48 ؋ 10 ؊13 ), miR-27a (P ‫؍‬ 4.15 ؋ 10 ؊12 ), and miR-9 (P ‫؍‬ 9.20 ؋ 10 ؊10 ). Finally, we identified strong correlations between 20 CpG sites and the histologic Mankin score in OA.Conclusion. Our data implicate epigenetic dysregulation of a host of genes and pathways in OA, including a number of OA susceptibility genes. Furthermore, we identified correlations between CpG methylation and histologic severity in OA.

A regenerated optical fibre Bragg grating that survives temperature cycling up to 1,295°C is demonstrated. A model based on seeded crystallisation or amorphisation is proposed.

Regenerated gratings seeded by type I gratings in boron-codoped germanosilicate optical fiber written with 193 nm are shown to withstand temperatures beyond 1000 degrees C.

Objective To perform a genome-wide DNA methylation study to identify differential DNA methylation patterns in subchondral bone underlying eroded and intact cartilage from patients with hip osteoarthritis (OA) and to compare these with DNA methylation patterns in overlying cartilage. Methods Genome-wide DNA methylation profiling using Illumina HumanMethylation 450 arrays was performed on eroded and intact cartilage and subchondral bone from within the same joint of 12 patients undergoing hip arthroplasty. Genes with differentially methylated CpG sites were analyzed to identify shared pathways, upstream regulators, and overrepresented gene ontologies, and these patterns were compared with those of the overlying cartilage. Histopathology was graded by modified Mankin score and assessed for correlation with DNA methylation. Results We identified 7,316 differentially methylated CpG sites in subchondral bone underlying eroded cartilage, most of which (~75%) were hypomethylated, and 1,397 sites in overlying eroded cartilage, 126 of which were shared. Samples clustered into 3 groups with distinct histopathologic scores. We observed differential DNA methylation of genes including the RNA interference–processing gene AGO2, the growth factor TGFB3, the OA suppressor NFATC1, and the epigenetic effector HDAC4. Among known susceptibility genes in OA, 32 were differentially methylated in subchondral bone, 8 were differentially methylated in cartilage, and 5 were shared. Upstream regulator analysis using differentially methylated genes in OA subchondral bone showed a strong transforming growth factor β1 signature (P = 1 × 10−40) and a tumor necrosis factor family signature (P = 3.2 × 10−28), among others. Conclusion Our data suggest the presence of an epigenetic phenotype associated with eroded OA subchondral bone that is similar to that of overlying eroded OA cartilage.

In light of recent proposals linking structural change and stresses within regenerated gratings, the details of regeneration of a seed Type-I Bragg grating written in H2 loaded germanosilicate fiber annealed at high temperatures (~900°C) are systematically explored. In particular, the influence of the strength of the grating, the effect of GeO2 doping concentration and the annealing conditions on regeneration are studied. We show that the role of dopants such as Ge and F contribute nothing to the regeneration, consistent with previous results. Rather, they may potentially be detrimental. Strongest regenerated gratings with R ~35% from a 5mm seed grating could be obtained in fibres with the lowest GeO2 concentrations such as standard telecommunications-compatible grade fibre.

No abstract

Strong regenerated gratings with a maximum grating strength exceeding (40-50) dB are fabricated inside an optical fibre by bulk macro thermal processing ∼ 900˚C using a UV-laser seeded Bragg grating. Further annealing between 1000˚C and 1100˚C leads to a stabilised grating ∼ 18 dB in strength. This suffers no further degradation at 1100˚C for the period monitored, over 4 hours. The potential resolution of this process is demonstrated by regenerating two complex profiles. Phase information is retained between seed and regenerated structures. This opens the way for nano-engineering of materials using thermal processing and seed templates.

No abstract