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Mannose-6-Phosphate, an Inhibitor of Transforming Growth Factor-β, Improves Range of Motion After Flexor Tendon Repair

Bates, Steven J. MD; Morrow, Ellen BS; Zhang, Andrew Y. MD; Pham, Hung BS; Longaker, Michael T. MD; Chang, James MD

Journal of Bone & Joint Surgery - American Volume: November 2006 - Volume 88 - Issue 11 - p 2465–2472
doi: 10.2106/JBJS.E.00143
Scientific Articles

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.

1 Stanford University Medical Center, 770 Welch Road, Suite 400, Stanford, CA 94304. E-mail address for J. Chang:

Copyright 2006 by The Journal of Bone and Joint Surgery, Incorporated
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