Background: Adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath results in a decreased postoperative range of motion in the hand. Transforming growth factor-beta (TGF-β) is a key cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of two natural inhibitors of TGF-β, decorin and mannose-6-phosphate, were investigated in vitro and in vivo.
Methods: In the in vitro investigation, primary cell cultures from rabbit flexor tendon sheath, epitenon, and endotenon were established and each was supplemented with TGF-β along with increasing doses of decorin or mannose-6-phosphate. Collagen-I production was measured with enzyme-linked immunosorbent assay (ELISA). For the in vivo study, rabbit zone-II flexor tendons were transected and then immediately repaired. Single intraoperative graded doses of decorin, mannose-6-phosphate, or phosphate-buffered saline solution (control) were added to the repair sites, and the forepaws were tested for the range of motion and repair strength at eight weeks postoperatively.
Results: Decorin and mannose-6-phosphate both reduced TGF-β upregulated collagen production. Intraoperative application of low-dose mannose-6-phosphate significantly improved the range of motion of the operatively treated digits. The effect on breaking strength of the tendon repair was inconclusive.
Conclusions: Mannose-6-phosphate is effective in reducing TGF-β upregulated collagen production in an in vitro model. This finding correlated with our in vivo finding that a single intraoperative dose of mannose-6-phosphate improved the postoperative range of motion.
Clinical Relevance: Mannose-6-phosphate is ubiquitous, nonimmunogenic, and easily produced, making it an ideal candidate for clinical application to reduce adhesion formation after flexor tendon repair.
In support of their research for or preparation of this manuscript, one or more of the authors received grants or outside funding from the Veterans Administration Merit Review Award. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Division of Plastic Surgery, Stanford University Medical Center, Stanford, and the Section of Plastic Surgery, VA Palo Alto Health Care System, Palo Alto, California
- Copyright © 2006 by The Journal of Bone and Joint Surgery, Incorporated
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