Effect of interleukin-10 overexpression on the properties of healing tendon in a murine patellar tendon model.
OBJECTIVE
Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine shown to inhibit scar formation in fetal wound healing. The role of IL-10 in adult tendon healing and scar formation, however, remains unknown. The objective of this study is to investigate the effect of IL-10 overexpression on the properties of adult healing tendon using a well-established murine model of tendon injury and a lentiviral-mediated method of IL-10 overexpression.


METHODS
A murine model of patellar tendon injury was used and animals divided into 3 groups. Mice received bilateral patellar tendon injections with a lentiviral vector containing an IL-10 transgene (n = 34) or no transgene (n = 34). Control mice (n = 34) received injections of sterile saline. All animals then were subjected to bilateral, central patellar tendon injuries 2 days after injection and were killed at 5, 10, 21, and 42 days after injury. IL-10 content was analyzed by immunohistochemistry (n = 4/group). Tendon healing was evaluated by histology (n = 4/group) and biomechanical analysis (n = 10/group).


RESULTS
Overexpression of IL-10 in patellar tendon was confirmed after injection of the lentiviral vector. IL-10 immunostaining was increased at day 10 in the IL-10 group relative to that in controls. Histologically, there was no significant difference in angular deviation between groups at day 21, but a trend toward decreased angular deviation in controls relative to that in empty vector group mice was seen at day 42. Biomechanically, the IL-10 group showed significantly increased maximum stress at day 42 relative to that in controls. Percent relaxation showed a trend toward an increase at day 10 and a significant increase at day 42 in the IL-10 group relative to that in controls.


CONCLUSIONS
This study demonstrates successful gene transfer of IL-10 into adult murine patellar tendon using a lentiviral vector. Although the effects of overexpression of IL-10 on adult tendon healing have not yet been fully elucidated, the current study may help to further clarify the mechanisms of tendon injury and repair.
Ricchetti
Eric T
ET
McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
Reddy
Sudheer C
SC
Ansorge
Heather L
HL
Zgonis
Miltiadis H
MH
Van Kleunen
Jonathan P
JP
Liechty
Kenneth W
KW
Soslowsky
Louis J
LJ
Beredjiklian
Pedro K
PK
D000818:Animals; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D016753:Interleukin-10 / Q000502:physiology*; D016086:Lentivirus; D008297:Male; D051379:Mice; D017847:Patellar Ligament / Q000293:injuries*; D013708:Tendon Injuries / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D016474:Weight-Bearing; D014945:Wound Healing / Q000502:physiology*
D016753:Interleukin-10