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

Koplin, Stephanie Ann MD; Su, Lillian DVM; Salamat, Shahriar MD, PhD; Torrealba, Jose MD; McCarthy, James MD; Mitchell, Jean BS, HT (ASCP); Olabisi, Ronke PhD; Noonan, Kenneth J. MD

Journal of Pediatric Orthopaedics: June 2011 - Volume 31 - Issue 4 - p 413–420
doi: 10.1097/BPO.0b013e31821adc8d
Bone Lengthening

Background Transforming growth factor-β 1 (TGF-β1) 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-β, 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-β1. 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-β1 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-β1 may not be the primary mediator of muscle fibrosis in distraction osteogenesis.

Clinical Relevance Injection of suramin may not prevent contracture formation after distraction osteogenesis.

Departments of *Pathology

Orthopaedics, University of Wisconsin School of Medicine and Public Health, Highland Avenue, Madison, WI

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI

Supported by the Orthopaedic Research and Education Fund (OREF).

Reprints: Stephanie Ann Koplin, MD, Department of Pathology, Aurora St. Lukes Hospital, 2900 W. Oklahoma Avenue, Milwaukee, WI, 53215. e-mail:

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.