Effect of exogenous IGF-1 on chondrocyte apoptosis in a rabbit intraarticular osteotomy model.
Insulin-like growth factor-1 (IGF-1) has been shown to protect chondrocytes from apoptosis in vitro. IGF-1 expression may also assist in maintaining a fully differentiated chondrocyte phenotype. Theoretically, posttraumatic administration of IGF-1 may inhibit chondrocyte apoptosis. This study is to determine if administration of IGF-1 after fracture inhibits apoptosis in vivo. Twenty-four mature female New Zealand white rabbits were randomized to control and IGF-1 groups. All subjects underwent standardized medial femoral condyle fracture and repair. Fibrin clot was administered in all subjects, with 25 mcg/ml IGF-1 in the clot in half the subjects. Half of the animals in each group were sacrificed at 2 weeks and half at 4 weeks, specimens were fixed and underwent TUNEL staining. Two-week controls showed significantly higher rate of apoptosis than 2-week IGF-1 subjects (21 +/- 6 vs. 12 +/- 6, p = 0.04). Likewise, 4-week controls showed significantly higher rate of apoptosis than 2-week IGF-1 subjects (23 +/- 7 vs. 10 +/- 2, p = 0.01). There was no significant administration difference between 2-week control and 4-week control subjects, or between 2-week IGF-1 and 4-week IGF-1 subjects. Intraarticular IGF-1 at the time of fracture repair appears to inhibit chondrocyte apoptosis in vivo, as judged by TUNEL staining, in this animal model. If administration of IGF-1 inhibits human chondrocyte apoptosis in vivo, this may lead to interventions that may reduce posttraumatic arthritis after fracture.
Higgins
Thomas F
TF
Department of Orthopaedics, University of Utah, 590 Wakara Way, Salt Lake City, Utah 84108, USA. thomas.higgins@hsc.utah.edu
Johnson
Brian D
BD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000601:surgery; D019902:Chondrocytes / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005269:Femur / Q000187:drug effects / Q000601:surgery; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D007719:Knee Joint / Q000187:drug effects / Q000601:surgery; D023421:Models, Animal; D010027:Osteotomy / Q000379:methods*; D011817:Rabbits; D011897:Random Allocation; D014945:Wound Healing
D007334:Insulin-Like Growth Factor I