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

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.