Matrix metalloproteinase-1 therapy improves muscle healing.
Muscle undergoes time-dependent phases of healing after injury, which ultimately results in residual fibrosis in the injured area. The use of exogenous matrix metalloproteinases (MMPs) may improve recovery after muscle injury by promoting the digestion of existing fibrous tissue and releasing local growth factors. In the current experiment, bilateral gastrocnemius (GM) lacerations were created in severe combined immunodeficient mice. Twenty-five days after injury (peak posttraumatic fibrosis), C2C12 cells (myoblasts) transduced with the LacZ reporter gene were injected with exogenous MMP-1 into the right GMs at the site of injury; the cells were also injected along with PBS (control) at the site of injury in the left GMs. The muscle tissues were examined histologically via X-gal, hemotoxylin and eosin, and Masson's trichrome staining. The MMP-treated limbs contained more regenerating myofibers than did the control limbs (MMP 170+/-96 fibers, control 62+/-51 fibers; P<0.001). Less fibrous tissue was observed within MMP-treated muscles (MMP: 24+/-11%, control: 35+/-15%; P<0.01). These results suggest that the direct injection of MMP-1 into the zone of injury during fibrosis can enhance muscle regeneration by increasing the number of myofibers and decreasing the amount of fibrous tissue.
Bedair
Hany
H
Stem Cell Research Center, Children's Hospital of Pittsburgh, Department of Orthopaedic Surgery, University of Pittburgh, 4100 Rangos Research Center, 3705 Fifth Ave., Pittsburgh, PA 15213-2583, USA.
Liu
T Thomas
TT
Kaar
Joel L
JL
Badlani
Shawn
S
Russell
Alan J
AJ
Li
Yong
Y
Huard
Johnny
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D020781:Matrix Metalloproteinase 1 / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries* / Q000473:pathology*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*; D014950:Wounds, Penetrating / Q000188:drug therapy* / Q000473:pathology*
D020781:Matrix Metalloproteinase 1