Proceedings of The Physiological Society

University of Manchester (2010) Proc Physiol Soc 19, PC291

Poster Communications

IGF-I increase skeletal muscle mass in arthritic rats by a direct effect on atrogin-1 and IGFBP-3 expression

M. Lopez-Menduiña1, A. Martin1, E. Castillero1, M. Villanua1, A. Lopez-Calderon1

1. Universidad Complutense, Madrid, Madrid, Spain.

Adjuvant arthritis is an animal model of rheumatoid arthritis that decreases liver and circulating IGF-I as well as skeletal muscle mass. Skeletal muscle wasting is associated with an accelerated protein degradation by muscle-specific ubiquitin ligases like atrogin-1. IGFBP-3 is a multifunctional protein that was reported to inhibit growth and enhance apoptosis. In this work we examined whether IGF-I administration is able to prevent the effect of arthritis on skeletal muscle. Furthermore, we evaluated whether IGF-I effects can be direct on skeletal muscle cells. Arthritis was induced in adult male Wistar rats by an intradermal injection in the sole of the right paw of 1 mg of complete Freund's adjuvant. On day 4 after adjuvant injection, control and arthritic rats were treated with IGF-I (100 μg/kg sc) twice a day, until day 15 when all rats were humanly killed. In order to test a direct IGF-I effect on muscle cells, L6 myoblasts cultures were incubated with IGF-I (10 ng/ml) during 1 and 4 hours. Atrogin-1 and IGFBP-3 gene expression were determined by real time PCR both in “in vivo” and “in vitro” studies. Arthritis decreased body weight gain as well as gastrocnemius weight (P<0.01), whereas increased atrogin-1 and IGFBP-3 gene expression in this muscle(P<0.01). In arthritic rats, IGF-I treatment increased body weight gain and gastrocnemius weight (P<0.05). Moreover IGF-I attenuated arthritis-induced increase in atrogin-1 and IGFBP-3 gene expression in the gastrocnemius muscle (P<0.05). In addition, in L6 myoblasts cultures, IGF-1 reduced both atrogin-1 (P<0.01) and IGFBP-3 (P<0.05) gene expression. These data suggest that IGF-I administration attenuates the inhibitory effect of chronic arthritis on skeletal muscle by decreasing atrogin-1 and IGFBP-3 gene expression, and that these IGF-I effects are exerted directly on skeletal muscle cells.

Where applicable, experiments conform with Society ethical requirements