Mannose-6-phosphate, an inhibitor of transforming growth factor-β, improves range of motion after flexor tendon repair

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

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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-1 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.

Original languageEnglish (US)
Pages (from-to)2465-2472
Number of pages8
JournalJournal of Bone and Joint Surgery - Series A
Volume88
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Transforming Growth Factors
Articular Range of Motion
Tendons
Decorin
Transforming Growth Factor beta
Collagen
Rabbits
Primary Cell Culture
mannose-6-phosphate
Sodium Chloride
Fibrosis
Hand
Enzyme-Linked Immunosorbent Assay
Phosphates
Cytokines
In Vitro Techniques

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Mannose-6-phosphate, an inhibitor of transforming growth factor-β, improves range of motion after flexor tendon repair. / Bates, Steven J.; Morrow, Ellen; Zhang, Andrew Y.; Pham, Hung; Longaker, Michael T.; Chang, James.

In: Journal of Bone and Joint Surgery - Series A, Vol. 88, No. 11, 11.2006, p. 2465-2472.

Research output: Contribution to journalArticle

Bates, Steven J. ; Morrow, Ellen ; Zhang, Andrew Y. ; Pham, Hung ; Longaker, Michael T. ; Chang, James. / Mannose-6-phosphate, an inhibitor of transforming growth factor-β, improves range of motion after flexor tendon repair. In: Journal of Bone and Joint Surgery - Series A. 2006 ; Vol. 88, No. 11. pp. 2465-2472.
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abstract = "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-1 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.",
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