Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and {beta}1 integrin expression in vitro

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2007.06.007· OSTI ID:21045916

Lluri, Gentian; Langlois, Garret D ^[1]; Soloway, Paul D ^[2]

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1. Department of Anatomy and Neurobiology, University of Vermont College of Medicine, 149 Beaumont Ave., HSRF 418, Burlington, VT 05405 (United States)
2. Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853 (United States)

Myogenesis in vitro involves myoblast cell cycle arrest, migration, and fusion to form multinucleated myotubes. Extracellular matrix (ECM) integrity during these processes is maintained by the opposing actions of matrix metalloproteinase (MMP) proteases and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Here, we report that TIMP-2, MMP-2, and MT1-MMP are differentially expressed during mouse myoblast differentiation in vitro. A specific role for TIMP-2 in myogenesis is demonstrated by altered TIMP-2{sup -/-} myotube formation. When differentiated in horse serum-containing medium, TIMP-2{sup -/-} myotubes are larger than wild-type myotubes. In contrast, when serum-free medium is used, TIMP-2{sup -/-} myotubes are smaller than wild-type myotubes. Regardless of culture condition, myotube size is directly correlated with MMP activity and inversely correlated with {beta}1 integrin expression. Treatment with recombinant TIMP-2 rescues reduced TIMP-2{sup -/-} myotube size and induces increased MMP-9 activation and decreased {beta}1 integrin expression. Treatment with either MMP-2 or MMP-9 similarly rescues reduced myotube size, but has no effect on {beta}1 integrin expression. These data suggest a specific regulatory relationship between TIMP-2 and {beta}1 integrin during myogenesis. Elucidating the role of TIMP-2 in myogenesis in vitro may lead to new therapeutic options for the use of TIMP-2 in myopathies and muscular dystrophies in vivo.

• OSTI ID: 21045916
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 314; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL CYCLE
HYPERTROPHY
IN VITRO
IN VIVO
MICE
PROTEOLYSIS