A common characteristic of ageing is disrupted homeostasis between growth and atrophy of skeletal muscle resulting in loss of muscle mass and function, which is associated with sarcopenia. Sarcopenia is related to impaired balance, increased falls and decline in quality of life of older people. Ageing-related transcriptome and proteome changes in skeletal muscle have been characterised, however the molecular mechanisms underlying sarcopenia are still not fully understood. microRNAs are novel regulators of gene expression known to modulate skeletal muscle development and homeostasis. Expression of numerous microRNAs is disrupted in skeletal muscle with age however, the functional consequences of this are not yet understood. Given that a single microRNA can simultaneously affect multiple signalling pathways, microRNAs are potent modulators of pathophysiological changes occurring during ageing. Here we use microRNA and transcript expression profiling together with microRNA functional assays to show that disrupted microRNA:target interactions play an important role in maintaining muscle homeostasis. We identified miR-181a as a regulator of the sirtuin1 (Sirt1) gene expression in skeletal muscle and show that the expression of miR-181a and its target gene is disrupted in skeletal muscle from old mice. Moreover, we show that miR-181a:Sirt1 interactions regulate myotube size. Our results demonstrate that disrupted microRNA:target interactions are likely related to the pathophysiological changes occurring in skeletal muscle during ageing.Electronic supplementary materialThe online version of this article (doi:10.1007/s10522-016-9638-8) contains supplementary material, which is available to authorized users.

Background and PurposeChondrocytes exist within cartilage and serve to maintain the extracellular matrix. It has been postulated that osteoarthritic (OA) chondrocytes lose the ability to regulate their volume, affecting extracellular matrix production. In previous studies, we identified expression of epithelial sodium channels (ENaC) in human chondrocytes, but their function remained unknown. Although ENaC typically has Na+ transport roles, it is also involved in the cell volume regulation of rat hepatocytes. ENaC is a member of the degenerin (Deg) family, and ENaC/Deg-like channels have a low conductance and high sensitivity to benzamil. In this study, we investigated whether canine chondrocytes express functional ENaC/Deg-like ion channels and, if so, what their function may be.Experimental ApproachCanine chondrocytes were harvested from dogs killed for unassociated welfare reasons. We used immunohistochemistry and patch-clamp electrophysiology to investigate ENaC expression and video microscopy to analyse the effects of pharmacological inhibition of ENaC/Deg on cell volume regulation.Key ResultsImmunofluorescence showed that canine chondrocytes expressed ENaC protein. Single-channel recordings demonstrated expression of a benzamil-sensitive Na+ conductance (9 pS), and whole-cell experiments show this to be approximately 1.5 nS per cell with high selectivity for Na+. Benzamil hyperpolarized chondrocytes by approximately 8 mV with a pD2 8.4. Chondrocyte regulatory volume decrease (RVI) was inhibited by benzamil (pD2 7.5) but persisted when extracellular Na+ ions were replaced by Li+.Conclusion and ImplicationsOur data suggest that benzamil inhibits RVI by reducing the influx of Na+ ions through ENaC/Deg-like ion channels and present ENaC/Deg as a possible target for pharmacological modulation of chondrocyte volume.

Teaching bioinformatics is a longstanding challenge for educators who need to demonstrate to students how skills developed in the classroom may be applied to real world research. This study employed an action research methodology which utilised student–staff partnership and peer-learning. It was centred on the experiences of peer-facilitators, students who had previously taken a postgraduate bioinformatics module, and had applied knowledge and skills gained from it to their own research. It aimed to demonstrate to peer-receivers, current students, how bioinformatics could be used in their own research while developing peer-facilitators’ teaching and mentoring skills. This student-centred approach was well received by the peer-receivers, who claimed to have gained improved understanding of bioinformatics and its relevance to research. Equally, peer-facilitators also developed a better understanding of the subject and appreciated that the activity was a rare and invaluable opportunity to develop their teaching and mentoring skills, enhancing their employability.

evidence for association (p<5*10-6). The two top hits were located near PCSK2 and ADAM33. We subsequently examined 17 previously identified genetic loci associated with hip OA. We observed that SNPs near RUNX2, ASTN2, FGF3 and COL11A1 were significantly associated to acetabular dysplasia. The most significant SNP was residing in COL11A1 ((p¼2*10-5), of which the previously identified risk allele hip OA was associated to a lower CE-angle indicative for more severe acetabular dysplasia. Interestingly, stratification according to age showed that the effect of the COL11A1-SNP was only present in relatively young individuals (age 65 or younger). Conclusions: Our study indicates that the CE-angle is highly suitable for genetic studies, given the fact that it can be reliably measured in large populations and of its continuous nature, which increases power to identify genetic associations. We here show results of the first genomewide association study on hip dysplasia. We identified several interesting candidate genes, which are currently being studied further. In addition, we identified a DNA variant in COL11A1 to be associated with acetabular dysplasia, which explains the association with hip OA. Interestingly, the association between the COL11A1 variant and hip dysplasia was driven by young individuals.

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