The Journal of Bone and Joint Surgery (American). 2006;88:2465-2472.
doi:10.2106/JBJS.E.00143
© 2006 The Journal of Bone and Joint Surgery, Inc.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow CME: Take the activities for this article:
 Basic Science Test 8: Winter 2007 (publication date February 15, 2007; expi...
CME 4: October, November, December 2006 (publication date January 5, 2007; ...
Right arrow Letters to the Editor: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Letters to the Editor are posted
Right arrow Alert me if a correction is posted
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bates, S. J.
Right arrow Articles by Chang, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bates, S. J.
Right arrow Articles by Chang, J.
Related Collections
Right arrow Basic Science
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Facebook   Add to Technorati   Add to Twitter  
What's this?

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

Steven J. Bates, MD1, Ellen Morrow, BS1, Andrew Y. Zhang, MD1, Hung Pham, BS1, Michael T. Longaker, MD1 and James Chang, MD1

1 Stanford University Medical Center, 770 Welch Road, Suite 400, Stanford, CA 94304. E-mail address for J. Chang: changhand{at}aol.com

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

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.

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Facebook Facebook   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
J. K.F. Wong, Y. H. Lui, Z. Kapacee, K. E. Kadler, M. W. J. Ferguson, and D. A. McGrouther
The Cellular Biology of Flexor Tendon Adhesion Formation: An Old Problem in a New Paradigm
Am. J. Pathol., November 1, 2009; 175(5): 1938 - 1951.
[Abstract] [Full Text] [PDF]

Home page
 Br Med BullHome page
A. Khanna, M. Friel, N. Gougoulias, U. G. Longo, and N. Maffulli
Prevention of adhesions in surgery of the flexor tendons of the hand: what is the evidence?
Br. Med. Bull., June 1, 2009; 90(1): 85 - 109.
[Abstract] [Full Text] [PDF]

Home page
 JBJSHome page
J. B. Tang, Y. Cao, B. Zhu, K.-Q. Xin, X. T. Wang, and P. Y. Liu
Adeno-Associated Virus-2-Mediated bFGF Gene Transfer to Digital Flexor Tendons Significantly Increases Healing Strength. An in Vivo Study
J. Bone Joint Surg. Am., May 1, 2008; 90(5): 1078 - 1089.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Ferdous, V. M. Wei, R. Iozzo, M. Hook, and K. J. Grande-Allen
Decorin-transforming Growth Factor- Interaction Regulates Matrix Organization and Mechanical Characteristics of Three-dimensional Collagen Matrices
J. Biol. Chem., December 7, 2007; 282(49): 35887 - 35898.
[Abstract] [Full Text] [PDF]