Delivery of a tissue derived extracellular matrix gel improves recovery following both acute and chronic disuse muscle injuries.
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ABSTRACT:
PROVIDER: PRJNA910573 | ENA |
REPOSITORIES: ENA
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Project description:To evaluate decellularized skeletal muscle extracellular matrix hydrogel effectiveness in treating disuse atrophy using a mouse hindlimb suspension (HU) model. Male C57BL/6J mice were subjected to 5 days of hind limb unloading then received intramuscular matrix gel on the left TA. We then performed gene expression profiling analysis using data obtained from RNA-seq from mouse TA muscles (n=4 for matrix gel treatment, n=4 for PBS control , and n=4 for uninjured control) at day 7 post matrix gel injection
2023-01-02 | GSE220641 | GEO
Project description:To evaluate decellularized skeletal muscle extracellular matrix hydrogel effectiveness in treating shoulder cuff tears using a rabbit (RI) model. Male New Zealand white rabbits had supraspinatus tendon severed and were housed for 12 weeks, after which they had tendon reattached and half of rabbits also received an extracellular matrix gel injection. We then performed gene expression profiling analysis using data obtained from RNA-seq from rabbit supraspinatus muscles (n=5 for repair+gel treatment, n=5 for repair only treatment , n=4 for injured control) at 2 weeks post and (n=5 for repair+gel treatment, n=5 for repair only treatment , n=5 for uninjured control) at 12 weeks post treatment
2022-12-30 | GSE221331 | GEO
Project description:Delivery of a tissue derived extracellular matrix gel modulates early fibro-adipogenic cell behavior and improves recovery following both acute and chronic disuse muscle injury.
| PRJNA913913 | ENA
Project description:Loss of muscle mass and strength following disuse followed by impaired muscle recovery likely contribute to sarcopenia in older adults. Metformin and leucine individually have shown positive effects in skeletal muscle during atrophy conditions but have not been evaluated in combination nor under the conditions of disuse atrophy and recovery in aging. The purpose of this study was to determine if a dual treatment of metformin and leucine (MET+LEU) would prevent disuse-induced atrophy and/or promote muscle recovery in aged mice (22-24 mo). We were also interested if these muscle responses correspond to changes in satellite cells and ECM abundance. Aged mice were subjected to 14 days of hindlimb unloading (HU) followed by 7 or 14 days of reloading (7 or 14d RL). Metformin (MET), leucine (LEU), or MET+LEU was administered via drinking water and were compared to Vehicle-treated mice. We observed that MET+LEU increased whole body grip strength, muscle specific force and satellite cell abundance during HU but did not alter muscle size during HU or RL. Moreover, MET+LEU treatment increased ECM turnover driven by a decrease in collagen IV content during 7 and 14d RL. Transcriptome analysis revealed that MET+LEU altered Gene Set Enrichment Analysis hallmark pathways related to inflammation and myogenesis during HU. Together , MET+LEU was able to improve muscle quality during disuse and recovery in aging possibly by increasing muscle satellite cell content and reducing excessive ECM accumulation.
2021-09-01 | GSE167462 | GEO
Project description:A mechanistic understanding of the age-related impairment to skeletal muscle regrowth following disuse atrophy as well as therapies to augment recovery in the aged are currently lacking. Mechanotherapy in the form of cyclic compressive loading has been shown to benefit skeletal muscle under a variety of paradigms, but not during the recovery from disuse in aged muscle. To determine whether mechanotherapy promotes extracellular matrix (ECM) remodeling, a critical aspect of muscle recovery after atrophy, we performed single cell RNA sequencing (scRNA-seq) of gastrocnemius muscle cell populations, stable isotope tracing of intramuscular collagen, and histology of the ECM in adult and aged rats recovering from disuse, with and without mechanotherapy. ECM remodeling-related gene expression in fibro-adipose progenitor cells (FAPs) was absent in aged compared to adult muscle following 7 days of recovery, and instead were enriched in chemoattractant genes. There was a significantly lower expression of genes related to phagocytic activity in aged macrophages during recovery, despite enriched chemokine gene expression of numerous stromal cell populations, including FAPs and endothelial cells. Mechanotherapy reprogrammed the transcriptomes of both FAPs and macrophages in aged muscle recovering from disuse to restore ECM-and phagocytosis-related gene expression, respectively. Stable isotope labeling of intramuscular collagen and histological evaluation confirmed mechanotherapy-mediated remodeling of the ECM in aged muscle recovering from disuse. In summary, our results highlight mechanisms underlying age-related impairments during the recovery from disuse atrophy and promote mechanotherapy as an intervention that reprograms the muscle transcriptional environment more similar to that of adult skeletal muscle.
2022-03-31 | GSE184413 | GEO
Project description:To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice. Genes that showed increased expression with unloading and a Bcl-3 peak in the promoter (from ChIP-seq data) were considered as Bcl-3 direct targets during disuse atrophy. Using ChIP array, we identified 241 direct targets for Bcl-3. Our data describe Bcl-3 as a global regulator both of the proteolysis and the change in energy metabolism that are essential components of muscle atrophy due to disuse. Disuse skeletal muscle atrophy was induced by hind limb unloading. Weight bearing (WB) or 5-day hind limb unloaded (HU) muscles were harvested for total RNA isolation and processed for whole transcript expression profiling. We chose to examine gene expression and Bcl-3 binding from 5-day unloaded muscles because our previous time course study of disuse atrophy suggested that most genes are differentially regulated at this time point, and thus, would best represent the time for Bcl-3 binding to the gene targets of the NF-kB transcriptional network.
2012-11-10 | E-GEOD-40578 | biostudies-arrayexpress
Project description:Aged skeletal muscle is characterized by impaired muscle recovery following disuse and coincides with an impaired muscle pro-inflammatory macrophage response. Macrophage inflammatory status (polarization) is regulated by its metabolic state, but to date, little is understood of macrophage metabolism and its relation to macrophage polarization in the context of muscle recovery and aging. Therefore, the purpose of this study was to thoroughly characterize macrophage metabolism and polarization in aged muscle during early recovery from disuse atrophy using single cell RNA sequencing and functional assays. Young (4-5 mo) and old (20-22 mo) male C57BL/6 mice underwent 14 days of hindlimb unloading followed by 4 days of ambulatory recovery. CD45+ cells were isolated from solei muscles and analyzed using 10x Genomics single cell RNA sequencing. We found that aged M1 macrophage clusters were characterized with an impaired inflammatory and glycolytic transcriptome and this impairment was accompanied by a suppression of HIF-1α and its immediate downstream target GLUT1.
2021-08-12 | GSE158987 | GEO
Project description:Disuse atrophy is a common clinical phenomenon which significantly impacts muscle function and activities of daily living. In this study, we did expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Keywords: Differentiation design
2007-08-28 | GSE8872 | GEO
Project description:Disuse atrophy is a common clinical phenomenon which significantly impacts muscle function and activities of daily living. In this study, we did expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Keywords: Differentiation design 28 Skeletal muscle biopsies from the medial gastrocnemius in patients with an ankle fracture (4 patients, 8 profiles) and from healthy volunteers (2 subjects, 4 profiles) subjected to 4-11 days of mobilization, as well as from the non-immobilized contralateral legs (16 profiles).
2007-08-28 | E-GEOD-8872 | biostudies-arrayexpress
Project description:To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice. Genes that showed increased expression with unloading and a Bcl-3 peak in the promoter (from ChIP-seq data) were considered as Bcl-3 direct targets during disuse atrophy. Using ChIP array, we identified 241 direct targets for Bcl-3. Our data describe Bcl-3 as a global regulator both of the proteolysis and the change in energy metabolism that are essential components of muscle atrophy due to disuse.
2012-11-10 | GSE40578 | GEO