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-ß) is a key
cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of
two natural inhibitors of TGF-ß, 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-ß 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
Results: Decorin and mannose-6-phosphate both reduced TGF-ß
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-ß
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.