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THE ROLE OF MMP-9 IN SATELLITE CELL ACTIVATION AFTER INCREASED ACTIVITY

Abstract

M. Pang1, G. McCall FACSM1, R. Mehan1, J-P. Hyatt2, J. Kim1

1University of Puget Sound, Tacoma, WA & 2Georgetown University, Washington, DC

The unique adaptive ability of skeletal muscle to meet functional demands is exemplified in its response to exercise. Though little is known about the molecular mechanisms that regulate this plasticity, the extracellular matrix (ECM) is believed to play a large role. The basal lamina is a specialized layer of ECM that lies in direct contact with the cell membrane of muscle fibers and facilitates environment-to-cell interactions. Matrix metalloproteinase-9 (MMP-9) is an enzyme in the basal lamina that is critical in ECM remodeling and may regulate much of these adaptive processes. Following exercise, the regenerative process of damaged muscle involves the activation of muscle-specific stem cells known as satellite cells. MMP-9 has been proposed to activate satellite cells, but no study has looked at this interaction to date. PURPOSE: The goals of the study were to: 1) determine the effects of MMP-9 satellite cell activity during muscle hypertrophy, and; 2) assess whether hypertrophy of the plantaris muscle observed after functional overload (FO) was due to the increased size of existing muscle fibers and/or the addition of new muscle fibers. METHODS: FO of the plantaris muscle, an ankle extensor, was performed by removing the soleus and gastrocnemius muscles in adult wild type (WT) and MMP-9 knockout (KO) mice. WT and KO mice were assigned to the following groups (n=5): 1) 2-day FO; 2) 14-day FO, and; 3) 0-day was used as a baseline control. Immunohistochemistry was performed using anti-Pax7 and anti-laminin antibodies to label satellite cells and the basal lamina, respectively. RESULTS: The average body weights (g) of WT and KO mice across all time points were 21.0 ± 0.49 and 20.5 ± 0.63, respectively. The mean ± SD absolute plantaris weights (mg) were as follows: 0-day WT 15.0 ± 0.85, 0-day KO 14.3 ± 1.76, 2-day WT 17.8 ± 0.80, 2-day KO 18.5 ± 0.87, 14-day WT 28.7 ± 3.52, and 14-day KO 24.0 ± 1.36. The mean absolute plantaris weight in the 14-day WT was 52% greater than 0-day WT. Preliminary data show that the number of satellite cells increased after 14-days FO compared to 0- and 2-day FO in both the WT and KO mice, while the total number of fibers appear unchanged among groups and time points. Additional muscles will be analyzed to determine if these differences achieve statistical significance. CONCLUSION: The current data suggest that hypertrophy of the plantaris is not due to: 1) MMP-9 mediated activation of satellite cells, or; 2) an increased number of muscle fibers.

Supported by the UPS Summer Research Grants in Science and Mathematics and the Phi Sigma grant.

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