IGF-I system, atrogenes and myogenic regulatory factors in arthritis induced muscle wasting

Mol Cell Endocrinol. 2009 Oct 15;309(1-2):8-16. doi: 10.1016/j.mce.2009.05.017. Epub 2009 Jun 6.

Abstract

The aim of this work was to analyse the evolution of the ubiquitin-proteasome, the myogenic regulatory factors, and the IGF-I system during the development of experimental arthritis. Arthritis was induced by adjuvant injection and rats were killed 10, 15 and 22 days later. Gastrocnemius was progressively atrophied in arthritic rats. Arthritis induced a rapid increase in muscular IGFBP-3 and IGFBP-5 and, to a lesser extent, in IGF-I mRNA. An increased expression of the muscle-specific ubiquitin ligases atrogin-1/MAFbx and MuRF-1 was observed in the gastrocnemius from day 10, reaching its maximum value on day 15. Concomitantly, the proliferation marker PCNA and the early myogenic regulatory factor MyoD were also maximally increased on day 15. Myogenin, a late-acting myogenic regulatory factor, was maximally increased on days 15 and 22. These results suggest that muscle wasting in arthritis is secondary to an increase in muscle proteolysis, rather to a decrease in muscle regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / complications*
  • Arthritis, Experimental / genetics*
  • Body Weight
  • Feeding Behavior
  • Gene Expression Regulation / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Protein 5 / genetics
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Interleukin-6 / blood
  • Male
  • Muscle Proteins / metabolism
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Myogenic Regulatory Factors / genetics
  • Myogenic Regulatory Factors / metabolism*
  • Myogenin / genetics
  • Myogenin / metabolism
  • Myostatin / genetics
  • Myostatin / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Wasting Syndrome / blood
  • Wasting Syndrome / etiology*
  • Wasting Syndrome / genetics*
  • Weight Gain

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 5
  • Interleukin-6
  • Muscle Proteins
  • MyoD Protein
  • Myogenic Regulatory Factors
  • Myogenin
  • Myostatin
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • Receptor, IGF Type 1