Skeletal muscle dysregulation in rheumatoid arthritis: Metabolic and molecular markers in a rodent model and patients.
Aged
Animals
Arthritis, Experimental
/ metabolism
Arthritis, Rheumatoid
/ complications
Biomarkers
Disease Models, Animal
Female
Glycogen
/ metabolism
Humans
Inflammation
Locomotion
Middle Aged
Muscle, Skeletal
/ metabolism
Muscular Diseases
/ etiology
Myalgia
/ etiology
RNA, Messenger
/ metabolism
Rats
Rats, Inbred Lew
Transcriptome
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
02
2020
accepted:
21
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
15
9
2020
Statut:
epublish
Résumé
Rheumatoid arthritis (RA) is accompanied by pain, inflammation and muscle weakness. Skeletal muscle inflammation and inactivity are independently associated with muscle insulin resistance and atrophy. Our objective was to identify early molecular and biochemical markers in muscle from a rodent model of RA relative to control and subsequently identify commonality in muscle gene expression between this model and muscle from RA patients. Pain behaviour and locomotor activity were measured in a collagen-induced arthritis (CIA) model of RA (n = 9) and control (n = 9) rats. Energy substrates and metabolites, total alkaline-soluble protein:DNA ratio and mRNA abundance of 46 targeted genes were also determined in Extensor digitorum longus muscle. Expression of targeted mRNAs was quantified in Vastus Lateralis muscle from RA patients (n = 7) and healthy age-matched control volunteers (n = 6). CIA rats exhibited pain behaviour (p<0.01) and reduced activity (p<0.05) compared to controls. Muscle glycogen content was less (p<0.05) and muscle lactate content greater (p<0.01) in CIA rats. The bioinformatics analysis of muscle mRNA abundance differences from the control, predicted the activation of muscle protein metabolism and inhibition of muscle carbohydrate and fatty acid metabolism in CIA rats. Compared to age-matched control volunteers, RA patients exhibited altered muscle mRNA expression of 8 of the transcripts included as targets in the CIA model of RA. In conclusion, muscle energy metabolism and metabolic gene expression were altered in the CIA model, which was partly corroborated by targeted muscle mRNA measurements in RA patients. This research highlights the negative impact of RA on skeletal muscle metabolic homeostasis.
Identifiants
pubmed: 32634159
doi: 10.1371/journal.pone.0235702
pii: PONE-D-20-03747
pmc: PMC7340297
doi:
Substances chimiques
Biomarkers
0
RNA, Messenger
0
Glycogen
9005-79-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0235702Subventions
Organisme : Medical Research Council
ID : MR/K00414X/1
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 18769
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 20777
Pays : United Kingdom
Organisme : Versus Arthritis
ID : 20843
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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