Compensatory anabolic signaling in the sarcopenia of experimental chronic arthritis

• Published in: Scientific reports Vol. 7; no. 1; pp. 6311 - 11
• Main Authors: Little, Robert D, Prieto-Potin, Iván, Pérez-Baos, Sandra, Villalvilla, Amanda, Gratal, Paula, Cicuttini, Flavia, Largo, Raquel, Herrero-Beaumont, Gabriel
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 24.07.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Arthritis; Arthritis, Experimental - complications; Arthritis, Experimental - metabolism; C-reactive protein; C-Reactive Protein - metabolism; Cachexia; Disease Models, Animal; Inflammation; Interleukin 6; Interleukin-1beta - metabolism; Male; MAP kinase; Metabolic Networks and Pathways; Muscles; MyoD protein; Myogenin; Myostatin; Myostatin - metabolism; NF-κB protein; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Proteolysis; Rabbits; Rheumatoid arthritis; Sarcopenia; Sarcopenia - etiology; Sarcopenia - metabolism; SKP Cullin F-Box Protein Ligases - metabolism; Synovium; Tripartite Motif Proteins - metabolism; Tumor necrosis factor; Up-Regulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-06581-6

Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). We characterized alterations to muscle structure and various pro-inflammatory, catabolic and regenerative markers in an animal model of RC. Antigen induced arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited significantly less weight gain, a markedly elevated serum C-reactive protein (CRP), lighter muscles with shorter cross-sectional diameter and increased myonuclei when compared to controls. Atrogin-1 and MuRF-1 were up-regulated alongside an increase in IL-1β, active NF-κB and a higher ratio of phosphorylated to inactive p38 MAPK. CCL-2 and TNF levels were reduced and IL-6 was unchanged between groups. We observed decreased pSTAT3, unchanged pSTAT1 and Myf5, but increased Pax7, MyoD and myogenin. AiA rabbits had a reduction in myostatin from gastrocnemii and synovium with a congruent decrease in serum myostatin compared to controls. Chronic arthritis induced an RC-like secondary sarcopenia with increased muscle protein breakdown. Elevated IL-1β may trigger proteolysis via elevated NF-κB and p38 MAPK signaling with a compensatory anabolic response suggested by myonuclear expansion, increased Pax7, MyoD and myogenin, reduced pSTAT3 as well as reduced serum, synovial and muscular myostatin.