The extracellular matrix (ECM) is an integral component in the structural support, force transmission, and maintenance of skeletal muscle. Following muscle injury or damage, the ECM assists in the degradation of damaged tissue and allows for the regeneration process to occur. A family of enzymes known as matrix metalloproteinases (MMPs) function to breakdown specific components of the ECM. MMP-9 and MMP-2 are the primary MMPs found in skeletal muscle that function to degrade small, network collagens. Cardiotoxin (CTX) is a snake venom that induces widespread and extensive damage throughout the targeted muscle. As such, CTX injection is an ideal model for studying the time course of muscle regeneration. PURPOSE: To determine the role of MMP-9 on skeletal muscle phenotype during regeneration in CTX-injected tibialis anterior (TA) muscles of wild type (WT) and MMP-9 knockout (KO) mice. METHODS: Adult female C57BL/6J wild type (WT) and MMP-9 knockout (KO) mice ~3 mos old were injected with 25 μL of 10 μM CTX along the longitudinal axis of the right TA muscle at three locations. The left TA was used as a contralateral control. At 3-wks post-CTX injury, the TA muscles were removed and 10 μm serial sections were stained for GPD, SDH, and ATPase to determine the muscle fiber phenotype. RESULTS: The mean body masses of the WT and MMP-9 KO mice were similar (22.2 ± 1.9 g vs. 19.0 ± 1.6 g, respectively). Although the absolute mean TA wet weight of the WT and MMP-9 KO mice were similar, the mean TA weight relative to body weight of the WT and MMP-9 KO CTX injured muscles mice were 33% and 19% greater (P<0.05) than their contralateral controls. Significant differences (P<0.05) in fiber phenotype occurred only in the superficial region of the CTX-injured TA. Specifically, MMP-9 KO CTX muscles had 51% fewer FOG and 81% greater FG fibers compared to WT CTX. CONCLUSION: The increased proportion of FG fibers in the superficial region suggests a shift towards a less oxidative TA phenotype in KO mice lacking MMP-9 expression.

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