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Oncotarget: Molecular signatures of chronic degeneration of shoulder muscles


Here is a link to a video interview with Dr. Vered Raz about this research on the Oncotarget YouTube Channel

Oncotarget published "Molecular signatures of age-associated chronic degeneration of shoulder muscles" which reported that shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration.

Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles.

Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles.

Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels.

The Oncotarget authors suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration.

Oncotarget authors suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration.

Dr. Vered Raz from The Leiden University Medical Center said, "Aging-associated muscle degeneration leads to functional impairments of daily activities of the elderly due to immobility and frailty."

Muscle degeneration is prominent in neuromuscular disorders and acute muscle disuse conditions.

Initially, studies focused on the tendon degeneration, but recently muscle degeneration has been suggested to be primarily involved in affected RC muscles.

In RC tears the supraspinatus muscle is initially affected and as the disease progresses, the subscapularis muscle can tear as well.

In chronic RC diseases the deltoid muscle is clinically not affected, and can be considered a reference muscle.

Figure 4: RNA expression profiles in deltoid and subscapularis muscle-derived cell cultures. A. Volcano plot shows log2 fold change (FC) versus -log10 of the p-value of all genes found in the RNA-seq (pair-wise analyses, n = 7). Red dots indicate significantly dysregulated genes (p < 0.05 FDR). Blue dots indicate dysregulated genes with a nominal p-value < 0.01. Positive or negative FC indicates higher or lower expression in subscapularis (SSc) compared with the deltoid (DM) cell cultures (CC). B. Functional gene ontology (GO) of dysregulated genes (p < 0.01), daughter GO clusters are connected with a line. GO clusters of muscle development are depicted in blue, in red the extracellular region, in green the inflammatory system and in yellow calcium binding. N indicates the number of genes. C. Box plot shows expression levels in SSc-CC or DM-CC for the most significantly dysregulated genes (p < 0.05 FDR). Fold changes between DM and SSc are depicted. Genes of the GO muscle development are marked in blue and those of the extracellular region in red. D. Representative images of fused SSc cell cultures transduced with either mock or MyoD lentivirus (LV). Myoblasts are stained with MyHC (white) and segmented in green. Nuclei are counterstained with DAPI (blue) and segmented in blue. Nuclei within segmented MyHC objects are marked in red. Scale bar is 200 μm. E. Plots show paired analyses of % of fused cells and total fused area between mock and MyoD LV in 4 SSc cell cultures. *: p-value < 0.05, using a paired T-test.

Shoulder surgery provides a unique opportunity for ex-vivo investigations of functionally impaired muscles compared with unaffected muscles.

The Raz Research Team concluded in their Oncotarget Research Paper that this an explorative study, with a small patient group and data have to be interpreted with caution.

An independent replication study to validate our results should be performed.

In this study they used muscle samples from shoulder pathology at an advanced stage.

In this stage the SSp is mostly torn, therefore the results presented here are an underestimation of muscle degeneration affecting only the SSp, which is more prevalent but less severe compared to tears extending to the SSc.

The more severe SSc pathology gives a broad spectrum to evaluate pathophysiological changes in chronic and torn muscles.

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DOI - https://doi.org/10.18632/oncotarget.7382

Full text - https://www.oncotarget.com/article/7382/text/

Correspondence to - Vered Raz - v.raz@lumc.nl

Keywords - shoulder disease, atrophy, fatty infiltration, muscle satellite cells, deep RNA-seq, Gerotarget

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