Compensatory anabolic signaling in the sarcopenia of experimental chronic arthritis

Sci Rep. 2017 Jul 24;7(1):6311. doi: 10.1038/s41598-017-06581-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / complications*
  • Arthritis, Experimental / metabolism
  • C-Reactive Protein / metabolism*
  • Disease Models, Animal
  • Interleukin-1beta / metabolism
  • Male
  • Metabolic Networks and Pathways*
  • Myostatin / metabolism
  • Phosphorylation
  • Rabbits
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Sarcopenia / etiology
  • Sarcopenia / metabolism*
  • Tripartite Motif Proteins / metabolism
  • Up-Regulation
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Interleukin-1beta
  • Myostatin
  • Tripartite Motif Proteins
  • C-Reactive Protein
  • SKP Cullin F-Box Protein Ligases
  • p38 Mitogen-Activated Protein Kinases