MMP-9 overexpression improves myogenic cell migration and engraftment.
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.
Morgan
Jennifer
J
UCL Institute of Child Health, 30 Guilford Street, London WC1N1EH, UK.
Rouche
Andrée
A
Bausero
Pedro
P
Houssaïni
Amal
A
Gross
Jacqueline
J
Fiszman
Marc Y
MY
Alameddine
Hala S
HS
D000818:Animals; D002459:Cell Fusion; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D017690:Cell Transplantation; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D024510:Muscle Development / Q000502:physiology*; D032446:Myoblasts / Q000201:enzymology / Q000502:physiology* / Q000637:transplantation*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D015854:Up-Regulation
D019714:Tissue Inhibitor of Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9