title: Original article Muscle extracellular matrix degradation and contractibility following tendon rupture and disuse.
abstract: Muscle extracellular matrix (ECM) plays an important role in maintaining muscular integrity and force transduction. However, the role of ECM in skeletal muscle atrophy remains unknown. In this study, we employed two clinically relevant mouse models of Achillotenotomy and hindlimb suspension to simulate Achilles tendon rupture and hindlimb disuse. The gastrocnemius was harvested following two weeks of treatment. We hypothesized that degradation of muscle ECM basement membrane lead to dysfunction of muscle contractility. Our results demonstrated a significant reduction of gastrocnemius single twitch force, isometric tetanic force, and contraction velocity following tendon rupture (p<0.001), but not disuse. Additionally, up-regulation of matrix metalloproteinase-2 (MMP-2) was observed only after tendon rupture (p=0.00234). These findings suggest that ECM remodeling and basement membrane degradation due to MMP-2 may be responsible for declined muscle contractibility. Inhibiting ECM degradation enzymes may be a potential treatment strategy for skeletal muscle atrophy after tendon rupture.
authors.affiliation: San Francisco Veterans Affairs (VA) Medical Center, San Francisco, California.
authors.forename: Qia
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Givenchy
authors.initials: G
authors.lastname: Manzano
authors.forename: David H
authors.initials: DH
authors.lastname: Lovett
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
keywords: Achillotenotomy; basement membrane; extracellular matrix; hindlimb suspension; matrix metalloproteinase-2; muscle atrophy