MMP-9 overexpression improves myogenic cell migration and engraftment.

Abstract

Myoblast migration requires matrix metalloproteinase (MMP) activity but the contribution of individual MMPs or tissue inhibitors of matrix metalloproteinase (TIMPs), particularly MMP-9 and TIMP-1, is lacking. Using two clones derived for differential regulation of MMP-2, MMP-9, and TIMP-1, we correlated protein expression with cell migration. MMP/TIMP regulation was determined by zymography, western blots, and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Cell migration was compared in vitro and after grafting into nude-mdx mouse muscles. C2M9 clones produced high MMP-9 and low MMP-2, and migrated better than C2F clones, which secreted low MMP-9, but overexpressed MMP-2 and TIMP-1. Improvement of C2F invasion by MMP-9 and inhibition of C2M9 migration by MMP-9 inhibitor I confirmed the role of MMP-9 and pointed to potential inhibition by TIMP-1. Higher complementation achieved by C2M9 grafts corroborated the beneficial effect of MMP-9 overexpression. Modulation of MMP-9 expression opens perspectives for improved efficacy of cell therapy for muscular dystrophies.

• Authors: Jennifer Morgan, Andrée Rouche, Pedro Bausero, Amal Houssaïni, Jacqueline Gross, Marc Y Fiszman, Hala S Alameddine
• Journal: Muscle & nerve (Muscle Nerve) Vol. 42 Issue 4 Pg. 584-95 (Oct 2010) ISSN: 1097-4598 [Electronic] United States
• PMID: 20734311 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tissue Inhibitor of Metalloproteinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Animals
• Cell Fusion
• Cell Line
• Cell Movement (physiology)
• Cell Transplantation
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, Nude
• Muscle Development (physiology)
• Myoblasts (enzymology, physiology, transplantation)
• Tissue Inhibitor of Metalloproteinases (metabolism)
• Up-Regulation