Matrix metalloproteinases (MMPs) are a group of enzymes involved in the formation and degradation of the extracellular matrix (ECM) proteins, a process required for proper skeletal muscle regeneration. MMP-9, a collagenase for type IV collagen, participates in multiple aspects of muscle remodeling; however, its specific function in regeneration is largely unknown. When the balance of ECM formation and degradation is altered such as occurs during injury and regeneration, irregular connective tissue composed mainly of collagen types I, III, and IV accumulates and results in scarring, known as fibrosis. PURPOSE: The primary goal of this study was to determine the role of MMP-9 in ECM remodeling and repair by quantifying the collagen content in the tibialis anterior (TA) muscle of wild type (WT) and MMP-9 knockout (KO) mice following cardiotoxin (CTX)-induced injury. METHODS: The right TA muscles of adult female WT and MMP-9 KO mice were injected with 25 µL of 10 µM CTX and allowed to recover for 1- or 2-wks. 10 µm cross-sections were stained with hematoxylin and eosin (H&E) and Picrosirius Red (PSR) to confirm muscle injury and determine collagen content, respectively. RESULTS: Post-CTX injection, mean relative TA muscle wet weights of WT mice at 1- and 2-wk were 0.186±0.007 and 0.273±0.014 mg/g (p<0.05) respectively. In MMP-9 KO mice, mean 2-wk post-CTX TA muscles were 31.4% and 18.8% heavier (p<0.05) than 1-wk and control, respectively. However, TA weight was 16.2% lighter (p<0.05) in KO than WT mice at 2-wk post-CTX. H&E staining revealed increased connective tissue and centrally located nuclei in WT and KO mice at 1-wk post-CTX that decreased after 2-wks. PSR staining showed that mean TA collagen content was similar post-CTX between groups at 30.85±5.08% for WT and 32.67±5.73% for KO at 1-wk and 26.73±6.46% for WT and 19.02±2.59% for KO at 2-wks. CONCLUSION: Collagen content similarly increased following CTX-induced injury in WT and KO mice, suggesting that MMP-9 may not be a primary contributor to CTX-induced fibrosis.

Supported by Sherman Fairchild Foundation and the Exercise Science Department at University of Puget Sound.

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