Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration

Abstract

Lei H, Leong D, Smith LR, Barton ER. Matrix metalloproteinase 13 is a new contributor to skeletal muscle regeneration and critical for myoblast migration. Am J Physiol Cell Physiol 305: C529-C538, 2013. First published June 12, 2013 doi:10.1152/ajpcell.00051.2013.-Efficient skeletal muscle repair and regeneration require coordinated remodeling of the extracellular matrix (ECM). Previous reports have indicated that matrix metalloproteinases (MMPs) play the pivotal role in ECM remodeling during muscle regeneration. The goal of the current study was to determine if the interstitial collagenase MMP-13 was involved in the muscle repair process. Using intramuscular cardiotoxin injections to induce acute muscle injury, we found that MMP-13 expression and activity transiently increased during the regeneration process. In addition, in muscles from mdx mice, which exhibit chronic injury, MMP-13 expression and protein levels were elevated. In differentiating C2C12 cells, a murine myoblast cell line, Mmp13 expression was most pronounced after myoblast fusion and during myotube formation. Using pharmacological inhibition of MMP-13 to test whether MMP-13 activity is necessary for the proliferation, differentiation, migration, and fusion of C2C12 cells, we found a dramatic blockade of myoblast migration, as well as a delay in differentiation. In contrast, C2C12 cells with stable overexpression of MMP-13 showed enhanced migration, without affecting myoblast maturation. Taken together, these results support a primary role for MMP-13 in myoblast migration that leads to secondary effects on differentiation.collagenase; matrix metalloproteinase; muscle repair; myoblast maturation

Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes

“…These cells get committed to myogenic differentiation and fuse with existing muscle fibers. [56][57][58][59][60][61] In vivo skeletal muscle growth is identified by hypertrophy (increase in fiber size) and hyperplasia (increase in fiber number), [62][63][64] while in vitro myogenic differentiation can be quantified by fusion index (ratio of fused nucleus) and area (hypertrophy) of myotubes. 42,43 In addition, maintenance of myotubes is influenced by signals of skeletal muscle protein Figure 1 sF-induced differentiation in hskMcs.…”

Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration

“…In our previous study, we have shown that FAPs are the major cellular source of adipocytes seen in RC muscles 25 . Lei et al 13 found that MMP-13 had an influence on the migration of satellite cells. But the role of MMP-13 on FAPs proliferation, migration and differentiation remains unknown.…”

“…MMP-13 has been shown to affect cellular migration, thus serving as a marker for metastatic cancers 12 . Upregulation of its activity in myoblast cell lines 13 suggests that it may affect the migration of satellite cells. Muscle fatty infiltration is believed be caused by fat progenitors migrating into the muscle following, resulting the buildup of fat 14 .…”

Keratocytes Create Stromal Spaces to Promote Corneal Neovascularization Via MMP13 Expression

“…After 7 consecutive days of treatment, the eyes were enucleated, and the corneas were dissected for zymogen extraction as previously reported. 19 The MMP13 activity of the rat corneas was detected via MMP13 assay kit according to the manufacturer's instructions.…”

“…We then investigated whether the inhibition of MMP13 activity using 444283 could attenuate new blood vessel formation in alkali-burned rat corneas; 444283 is a derivative of pyrimidine dicarboxamide, and it very selectively inhibits MMP13 activity. 19,30,31 It has been demonstrated to efficiently and specifically inhibit MMP13 activity in cultured C2C12 cells at a concentration of 10 lM. 19 To demonstrate that 444283 can also inhibit MMP13 activity in alkali-burned rat corneas and determine the concentration of this inhibitor to use for topical administration, rats were given 444283 concentrations of 50, 100, and 200 lM or saline topically for 7 days after alkali burns.…”