Distraction Osteogenesis-Induced Muscle Fibrosis May Not Be Associated With TGF-β1

Background: Transforming growth factor-beta 1 (TGF-beta 1) participates in the synthesis and deposition of collagen. It has been implicated in fibrosis of tendons in wound-healing models but has never been studied in muscles with respect to distraction osteogenesis. Methods: Using a rabbit model of distraction osteogenesis, we distracted the left tibias of 36 New Zealand white rabbits at 0.75 mm/d for 20 days. To determine whether suramin, an antagonist of TGF-beta, could aid in the prevention of fibrosis, we injected it into the anterior tibialis muscle [12 rabbits received low-dose suramin (50 mg), 12 received high-dose suramin (100 mg), and 12 received sham injections]. Half of each group was killed at the end of distraction (day 24) and the other half at day 60. At the time of killing the rabbits, joint range of motion was measured, and strength and morphometric measures of the muscle were taken. Muscle was harvested and immunolabeled for TGF-beta 1. All findings were compared between study limbs and control (right) limbs. Results: The comparison failed to demonstrate improvements in the range of motion, and in strength or morphometric muscle development. Immunolabeling for TGF-beta 1 failed to show any staining in the intramuscular fibrosis. Paradoxically, muscle injected with high-dose suramin had the highest degree of fibrosis. Conclusions: We conclude that TGF-beta 1 may not be the primary mediator of muscle fibrosis in distraction osteogenesis.