Myostatin, insulin-like growth factor-1, and leukemia inhibitory factor mRNAs are upregulated in chronic human disuse muscle atrophy

Human disuse muscle atrophy frequently accompanies orthopedic injury, arthr itis, or bed rest, and recovery is often incomplete despite current rehabil itation programs. We have studied the vastus lateralis muscle in 12 patient s with chronic disuse atrophy associated with chronic osteoarthritis of the hip both preoperatively and after total hip arthroplasty. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated an i ncrease in the level of expression of myostatin, insulin-like growth factor -1 (IGF-1) and leukemia inhibitory factor (LIF) mRNAs compared to healthy c ontrol muscle. In all patients there was a significant correlation preopera tively between increasing myostatin mRNA expression and reduction in type 2 A and 2B fiber area. In the 8 female patients there was a significant corre lation between increased myostatin mRNA expression and the atrophy factor c alculated for 2A and 2B fiber types preoperatively. We hypothesize that a c omplex interaction occurs between muscle growth regulating factors in the g enesis of muscle wasting. Our results indicate that myostatin is a muscle-w asting factor contributing to type 2B and 2A atrophy. Other muscle growth f actors, such as IGF-1 and LIF, may be upregulated in a counterregulatory fa shion or may be involved in the fiber type switching seen in disuse muscle wasting. (C) 2001 John Wiley & Sons, Inc.