Abstract
Matrix metalloproteinase‐2 (MMP‐2) appears to be the dominant MMP activated during skeletal muscle atrophy. However, little is known about cell‐specific regulatory mechanisms of MMP‐2 transcription in vivo. In this study, we used a mouse model of muscle atrophy induced by complete Achilles tendon transection. Time‐dependent muscle weight loss, nuclei density reduction, and extracellular matrix degeneration were observed consistently after Achilles tendon transection. Increased MMP‐2 expression was confirmed at the mRNA and protein level. Experiments using transgenic mice with a MMP‐2 promoter/enhancer reporter construct demonstrated markedly increased MMP‐2 promoter/enhancer activity in atrophic skeletal muscle. Tissue‐specific upregulation of MMP‐2 promoter activity was observed not only in myocytes, but also in blood vessels, nerve, and fascia. The transcription factors c‐Jun and FosB were expressed at high levels in atrophic muscle, suggesting a role in MMP‐2 upregulation. These findings show that increased MMP‐2 activity in disused atrophic muscle and supporting tissues is regulated, at least in part, by increased MMP‐2 promoter/enhancer activity. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:357–363, 2008