Matrix Metalloproteinase-9 Deficiency Results in Decreased Fiber Cross-Sectional Area and Alters Fiber Type Distribution in Mouse Hindlimb Skeletal Muscle

Abstract

Matrix metalloproteinases (MMPs) play a major role in the degradation of the extracellular matrix (ECM) of skeletal muscle, and the inducible gelatinase MMP-9 in particular appears to be critical for the remodeling of muscle ECM during growth and repair. Here we determined the effects of MMP-9 gene inactivation on fiber type and size in the tibialis anterior (TA), gastrocnemius (GAST), and soleus (SOL) muscles in female mice. In the TA, the cross-sectional area (CSA) of the myosin heavy chain (MyHC) IIb-expressing fibers was significantly smaller in MMP-9 null mice while in the GAST, CSA of all three fast fiber types was decreased. In the SOL, MyHC type I-expressing fibers were significantly smaller in the MMP-9 null mice. The percentage of MyHC type IIb-expressing fibers was significantly increased in the TA and GAST of MMP-9 null mice, while the percentage of MyHC IId-expressing fibers significantly decreased in the GAST of MMP-9 null mice. Fiber percentages in the SOL were not significantly different between the two lines. Despite these changes in fiber size and type, in vivo hindlimb force production was not changed in MMP-9 null mice. Meanwhile, neither expression of the constitutive gelatinase MMP-2 nor immunohistochemical staining for type IV collagen was significantly altered by MMP-9 inactivation in any muscles examined. The present study demonstrates that MMP-9 inactivation results in changes in fiber size and type in adult mouse hindlimb muscles that may depend on indirect mechanisms involving reduced bone growth or nerve changes in response to MMP-9 inactivation.