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-beta) is a key cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of two natural inhibitors of TGF-beta, 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-beta 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-beta 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-beta 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.
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-beta) is a key cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of two natural inhibitors of TGF-beta, 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-beta 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-beta 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-beta 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.
Authors: Jason K F Wong; Yin H Lui; Zoher Kapacee; Karl E Kadler; Mark W J Ferguson; Duncan A McGrouther Journal: Am J Pathol Date: 2009-10-15 Impact factor: 4.307
Authors: Hacı Bayram Tosun; Seyit Ali Gümüştaş; Mustafa Kom; Abuzer Uludağ; Sancar Serbest; Yesari Eröksüz Journal: Balkan Med J Date: 2016-05-01 Impact factor: 2.021
Authors: Evan B Katzel; Matthew Wolenski; Alayna E Loiselle; Patrick Basile; Lisa M Flick; Howard N Langstein; Matthew J Hilton; Hani A Awad; Warren C Hammert; Regis J O'Keefe Journal: J Orthop Res Date: 2010-09-14 Impact factor: 3.494
Authors: Alayna E Loiselle; Kiminori Yukata; Michael B Geary; Sirish Kondabolu; Shanshan Shi; Jennifer H Jonason; Hani A Awad; Regis J O'Keefe Journal: J Orthop Res Date: 2015-06 Impact factor: 3.494