THE ROLE OF MMP-2, 9, AND 13, IN THE REGULATION OF SKELETAL MUSCLE HYPERTROPHY

R.E. Fitzpatrick1, G.E. McCall1, R.S. Mehan1, J. Hyatt2, J.A. Kim1 1University of Puget Sound, Tacoma, WA & 2Georgetown University, Washington, DC PURPOSE: Skeletal muscle is the most abundant tissue in vertebrates that functions primarily to generate locomotion, and exhibits a high degree of structural and functional plasticity that is largely dependent on the level of activity placed on it. Recent studies have shown that a family of enzymes known as matrix metalloproteinases (MMPs) play an important role in regulating this plasticity. Specifically, MMP-2, -9, and -13 degrade components of the extracellular matrix (ECM) surrounding muscle fibers during periods of growth and repair. However, the mechanisms by which these MMPs mediate this response and how each contributes to muscle repair and remodeling remains largely unknown. The purpose of this study was to examine the relationship between MMP-2, -9, and -13 in functionally overloaded (FO) mouse plantaris muscle, and determine what effect the absence of MMP-9 has on the expression of MMP-2 and MMP-13 in hypertrophying muscle. METHODS: FO of the plantaris muscle was performed on 10 wild type (WT) and 10 MMP-9 knockout (KO) mice. The plantaris muscle was then harvested at baseline (0-day), and 2- and 14-days after FO. RT-PCR experiments were performed to determine the semi-quantitative mRNA expression levels of MMP-2, -9, and -13. RESULTS: The mean relative plantaris muscle weight after 14-days FO was 1.0 ± 0.23 mg/g and 1.2 ± 0.25 mg/g in the WT and MMP-9 KO mice, respectively, and this was significantly larger compared to their respective 0-day baseline controls (p\u3c0.05). MMP-2 and MMP-13 mRNA expression in WT mice was 5.7 and 4.8% higher, respectively, after 14-days FO compared to baseline control. Similarly, MMP-2 and MMP-13 mRNA in MMP-9 KO mice after 14-days FO was 4.1 and 6.6% higher, respectively, compared to baseline control. CONCLUSIONS: MMP-2 and MMP-13 may play a more central role in hypertrophy than MMP-9. Additionally, there was no early expression of MMP-2 or MMP-13 in the KO mice, suggesting another molecular marker may be compensating for MMP-9 or that MMP-9 may not be essential in hypertrophy following FO. Supported by the McCormick Scholar Award and funds awarded to Dr. Kim from the University Enrichment Committee