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Article Title

THE ROLE OF MMP-9 IN MOUSE PLANTARIS MUSCLE HYPERTROPHY

Abstract

Skeletal muscle extracellular matrix (ECM) is integral to various cellular behaviors. The gelatinases are a subfamily of zinc-dependent proteases called matrix metalloproteinases (MMPs) that degrade ECM proteins. MMP-9 primarily degrades type IV collagen, a component of the myofiber basal lamina. MMP-9 expression increases during remodeling conditions, such as load-inducing hypertrophy. PURPOSE: To investigate the hypertrophy response of the plantaris in C57 wildtype (WT) and MMP-9 knockout (KO) mice after 2 and 14 days of functional overload (FO) induced hypertrophy. METHODS: C57 wildtype (Harlan Labs) and KO (Jackson Labs) mice (age:10-14 weeks) underwent FO of the plantaris muscle using the bilateral synergist ablation model in which the medial and lateral gastrocnemii were surgically isolated and removed. After 2 or 14 days of FO, mice (n=6-11/group) were euthanized and the plantaris was removed bilaterally, weighed, frozen, and stored at -80°C. A two-way ANOVA (time x group) was used to compare mean relative plantaris weight (mg/g of body weight) among groups. Significance was set at p≤0.05. RESULTS: Mean ± SD relative plantaris weights were similar between WT and KO groups (main effect p=0.407; 0.068 ± 0.006 and 0.074 ± 0.015 mg/g at baseline, respectively). For both WT and KO groups, significant hypertrophy occurred (main effect p<0.0001) after 2 day FO (0.091 ± 0.012 and 0.077 ± 0.005 mg/g, respectively) and continued through 14 day (0.110 ± 0.020 and 0.105 ± 0.027 mg/g, respectively). However, the hypertrophy response was similar among groups (interaction p=0.254). CONCLUSIONS: Inactivation of the MMP-9 gene did not affect the increase in relative muscle plantaris wet weight response to FO. To further understand the cellular hypertrophy response, ongoing analysis is focused on the quantification of the plantaris type IV collagen content by immunohistochemistry.

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