Total Elbow Arthroplasty

Total elbow arthroplasty has continued to evolve over time. Elbow implants may be linked or unlinked. Unlinked implants are attractive for patients with relatively well preserved bone stock and ligaments, but many favor linked implants, since they prevent instability and allow replacement for a wider spectrum of indications. Inflammatory arthropathies such as rheumatoid arthritis represent the classic indication for elbow arthroplasty. Indications have been expanded to include posttraumatic osteoarthritis, acute distal humerus fractures, distal humerus nonunions and reconstruction after tumor resection. Elbow arthroplasty is very successful in terms of pain relief, motion and function. However, its complication rate remains higher than arthroplasty of other joints. The overall success rate is best for patients with inflammatory arthritis and elderly patients with acute distal humerus fractures, worse for patients with posttraumatic osteoarthritis. The most common complications of elbow arthroplasty include infection, loosening, wear, triceps weakness and ulnar neuropathy. When revision surgery becomes necessary, bone augmentation techniques provide a reasonable outcome

Widespread recovery of methylation at gametic imprints in hypomethylated mouse stem cells following rescue with DNMT3A2

BACKGROUND: Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated region (gDMR). Previous studies have indicated that DNA methylation lost from gDMRs could not be restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating that imprinted regions must instead undergo passage through the germline for reprogramming. However, previous studies were non-quantitative, were unclear on the requirement for DNMT3A/B and showed some inconsistencies. In addition, new putative gDMR has recently been described, along with an improved delineation of the existing gDMR locations. We therefore aimed to re-examine the dependence of methylation at gDMRs on the activities of the methyltransferases in mouse embryonic stem cells (ESCs). RESULTS: We examined the most complete current set of imprinted gDMRs that could be assessed using quantitative pyrosequencing assays in two types of ESCs: those lacking DNMT1 (1KO) and cells lacking a combination of DNMT3A and DNMT3B (3abKO). We further verified results using clonal analysis and combined bisulfite and restriction analysis. Our results showed that loss of methylation was approximately equivalent in both cell types. 1KO cells rescued with a cDNA-expressing DNMT1 could not restore methylation at the imprinted gDMRs, confirming some previous observations. However, nearly all gDMRs were remethylated in 3abKO cells rescued with a DNMT3A2 expression construct (3abKO + 3a2). Transcriptional activity at the H19/Igf2 locus also tracked with the methylation pattern, confirming functional reprogramming in the latter. CONCLUSIONS: These results suggested (1) a vital role for DNMT3A/B in methylation maintenance at imprints, (2) that loss of DNMT1 and DNMT3A/B had equivalent effects, (3) that rescue with DNMT3A2 can restore imprints in these cells. This may provide a useful system in which to explore factors influencing imprint reprogramming. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-016-0104-2) contains supplementary material, which is available to authorized users