Project description:Transcripts were measured in infraspinatus muscle before (PRE) and after 16 weeks of tendon release (TR) and 6 weeks of subsequent repair (END) in the operated and contralateral (END-CC) muscle. A group of animals received intramuscular injections of nandrolone starting with the surgery (N22W). In another group injection of nandrolone was started at the time of tendon repair (N6W). The CONTROL group received no nandrolone.
Project description:Metabolites and lipid species were measured using ultrahigh performance lipid chromatography – tandem mass spectrometry in biopsies of infraspinatus muscle after 2 weeks of tendon release in the operated and contralateral muscle. A group of animals received oral treatment with L-carnitine.
Project description:Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied immediately after tendon release. The effects of infraspinatus tendon release and subsequent tendon repair at 16 weeks were studied in six Swiss Alpine sheep. In the interventional groups, 150mg nandrolone was administered weekly after tendon release until sacrifice (N22W, n=6) or starting at the time of repair (N6W, n=6). Infraspinatus volume, composition, expressed transcripts, lipids, and selected proteins were analyzed at baseline, 16 and 22 weeks. Tendon release reduced infraspinatus volume by 22% and increased fat content from 11% to 38%. These changes were not affected by repair. Fatty infiltration was associated with up-regulation of 227 lipid species, and increased levels of the adipocyte differentiation marker PPARG2 (peroxisome proliferator-activated receptor gamma 2). Nandrolone abrogated lipid accumulation, halved the loss in fiber area percentage, and up-regulated androgen receptor levels and transcript expression in the N22W but not the N6W group. The results document that nandrolone mitigates muscle-to-fat transformation after tendon release via a general down-regulation of lipid accumulation concomitantly with up-regulated expression of its nuclear receptor and downstream transcripts in skeletal muscle. Reduced responsiveness of retracted muscle to nandrolone as observed in the N6W group is reflected by a down-regulated transcript response.
Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS322 Abstract:Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied immediately after tendon release. The effects of infraspinatus tendon release and subsequent tendon repair at 16 weeks were studied in six Swiss Alpine sheep. In the interventional groups, 150mg nandrolone was administered weekly after tendon release until sacrifice (N22W, n=6) or starting at the time of repair (N6W, n=6). Infraspinatus volume, composition, expressed transcripts, lipids, and selected proteins were analyzed at baseline, 16 and 22 weeks. Tendon release reduced infraspinatus volume by 22% and increased fat content from 11% to 38%. These changes were not affected by repair. Fatty infiltration was associated with up-regulation of 227 lipid species, and increased levels of the adipocyte differentiation marker PPARG2 (peroxisome proliferator-activated receptor gamma 2). Nandrolone abrogated lipid accumulation, halved the loss in fiber area percentage, and up-regulated androgen receptor levels and transcript expression in the N22W but not the N6W group. The results document that nandrolone mitigates muscle-to-fat transformation after tendon release via a general down-regulation of lipid accumulation concomitantly with up-regulated expression of its nuclear receptor and downstream transcripts in skeletal muscle. Reduced responsiveness of retracted muscle to nandrolone as observed in the N6W group is reflected by a down-regulated transcript response.
Project description:Amniotic derived cells are ideal seed cells for regenerative medicine protocols since they conjugate a remarkable plasticity to safety properties. This study investigated the role exerted by human amniotic cells during the process of tendon healing. In particular, in the present research it has been evaluated, by microarray technique, the presence of transcriptome variations in human amniotic epithelial (hAECs) and mesenchymal (hAMCs) stem cells when xenotransplanted into the preclinical ovine model of tendon defect, compared to freshly isolated ones. This analysis allowed to understand in which way, after 28 days transplantation, hAECs and hAMCs transcripts have been affected. Total of 4 experiments.Two-condition experiment, Human amniotic stem cells xenotransplantated in a sheep achilles tendon vs.HAEC/HAMC Biological replicates: 2 Xenotrasplatations. One replicate per array.
Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon RNA was extracted and anlyzed.
Project description:This microarray study compared the gene expression profile of rat tail tendon tissue in three different developmental stages: embryonic day 21, postnatal 3 weeks and postnatal 6 weeks.<br><br><br><br>Key words: rat tail tendon, tissue development, embryonic and postnatal
Project description:Chronic rotator cuff (RC) tears are characterized by retraction, fat accumulation, and atrophy of the affected muscle. These features pose an intractable problem for surgical repair and subsequent recovery, and their prevention may be easier than reversal. Using an established ovine model, we tested the hypothesis that inhibition of the protease calpain mitigates m. infraspinatus atrophy by preservation of the myofibers' structural anchors in the sarcolemma (the costameres). Already 2 weeks of distal tendon release led to a reduction in muscle volume (-11.6 ± 9.1 cm3 , P = 0.038) and a 8.3% slow-to-fast shift of the fiber area (P = 0.046), which were both entirely abolished by chronic local administration of the calpain inhibitor calpeptin alone, and in combination with sildenafil. Calpain inhibition blunted the retraction of the muscle-tendon unit by 0.8-1.0 cm (P = 0.020) compared with the control group, and prevented cleavage of the costameric protein talin. Calpain 1 and 2 protein levels increased in the medicated groups after 4 weeks, counteracting the efficacy of calpeptin. Hence atrophic changes emerged after 4 weeks despite ongoing treatment. These findings suggest that the early muscular adaptations in the specific case of RC tear in the ovine model are indistinguishable from the atrophy and slow-to-fast fiber transformation observed with conventional unloading and can be prevented for 2 weeks. Concluding, calpain is a potential target to extend the temporal window for reconstruction of the ruptured RC tendon before recovery turns impossible.
Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon DNA was extracted and anlyzed. Genome-wide DNA methylation profiles were determinen. DNA amplicons were prepared using Differential Methylation Hybridization (DMH) method, subsequently hybridized on to the Customized Agilent Rat CpG island Microarray. The goal was to unravel the DNA methylation patterns in different subgropus of tendon tissue according to partciulate matter exposure.