Systemic IGF-I administration attenuates the inhibitory effect of chronic arthritis on gastrocnemius mass and decreases atrogin-1 and IGFBP-3.
Adjuvant arthritis is an animal model of rheumatoid arthritis that decreases liver and circulating IGF-I as well as skeletal muscle mass. The aim of this work was to elucidate whether IGF-I administration was able to prevent the effect of arthritis on body weight and on two skeletal muscles, gastrocnemius and soleus. On day 4 after adjuvant injection, control and arthritic rats were treated with IGF-I (100 microg/kg s.c.) two times a day, until day 15 when all rats were killed. Arthritis decreased body weight gain and gastrocnemius weight. In arthritic rats, IGF-I treatment increased body weight gain and gastrocnemius weight, without modifying food intake or the external signs of arthritis. Arthritis increased atrogin-1 and muscle ring finger 1 (MuRF1) gene expression in the gastrocnemius and to a lesser extent in the soleus muscle. IGF-I attenuated the arthritis-induced increase in atrogin-1 and MuRF1 expression in the gastrocnemius, whereas it did not modify the expression of these genes in the soleus muscle. Arthritis also increased IGF-binding protein (IGBP)-3 and IGFBP-5 gene expression in gastrocnemius and soleus, whereas IGF-I administration decreased IGFBP-3, but not IGFBP-5, gene expression in both muscles. In both groups of arthritic rats and in control rats treated with IGF-I, proliferating cell nuclear antigen and myogenic differentiation proteins were increased in the gastrocnemius. These data suggest that the inhibitory effect of chronic arthritis on skeletal muscle is higher in fast glycolytic than in slow oxidative muscle and that IGF-I administration attenuates this effect and decreases atrogin-1 and IGFBP-3 gene expression.
Faculty of Medicine, Department of Physiology, Complutense University of Madrid, Madrid, Spain.
María
M
López-Menduiña
Ana Isabel
AI
Martín
Estíbaliz
E
Castillero
María Angeles
MA
Villanúa
Asunción
A
López-Calderón
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D001835:Body Weight; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation; D006019:Glycolysis; D006801:Humans; D007279:Injections, Subcutaneous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D009161:Mycobacterium; D017570:MyoD Protein / Q000378:metabolism; D009929:Organ Size; D010084:Oxidation-Reduction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D012720:Severity of Illness Index; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D009124:Muscle Proteins; D017570:MyoD Protein; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D000070584:Tripartite Motif Proteins; D007334:Insulin-Like Growth Factor I; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases