Skeletal muscle dysregulation in rheumatoid arthritis: Metabolic and molecular markers in a rodent model and patients

Abstract

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.

Phenolic-Compound-Rich Opuntia littoralis Ethyl Acetate Extract Relaxes Arthritic Symptoms in Collagen-Induced Mice Model via Bone Morphogenic Markers

“…Our results showed that the arthritic mice lost weight compared to the healthy controls. These results support earlier research indicating that chronic arthritis frequently results in weight loss due to the systemic or local activity of inflammatory cytokines such as TNF-α and IL-1β, which are produced predominantly by the monocytes and macrophages that cause muscle degeneration and loss of appetite [50,51]. Our study demonstrated that administering OL-EAE to CIA mice resulted in weight gain.…”

Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis

“…Therefore, it is difficult to separate the energy-generating functions of fatty acids in the mitochondria from other roles in RA based solely on abundance measurements. Changes in fatty acid metabolism may also perpetuate extra-articular symptoms of RA, for example differential expression of enzymes involved in fatty acid metabolism were observed in skeletal muscle tissue in an arthritis model and RA patients ( 96 ).…”

Effects of aerobic and resistance exercise in murine models of rheumatoid arthritis and osteoarthritis – a systematic review

“…This systemic inflammation can also lead to secondary sarcopenia, which appears to be primarily driven by catabolic processes. When systemic inflammation persists and is associated with anorexia, asthenia, and/or physical inactivity, additional muscle loss pathways are activated, altering the balance of muscle tissue remodelling, and may activate different intracellular proteolysis pathways [3][4][5].…”