Inhibition of TGF-β-induced collagen production in rabbit flexor tendon with mannose-6-phosphate in vitro.
The flexor tendon affects postoperative range of motion in the hand. Transforming growth factor-beta (TGF-β) is a key cytokine in the adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath. The purpose of this study was to examine the inhibition of TGF-β-induced collagen-I production in rabbit flexor tendons with mannose-6-phosphate in vitro. Sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes from rabbit flexor tendons were isolated and each was supplemented with TGF-β along with increasing doses of mannose-6-phosphate. The enzyme-linked immunosorbent assay (ELISA) and reverse-transcription polymerase chain reaction (RT-PCR) measured collagen-I production. The luciferase assay measured TGF-β bioactivity. Results were compared with TGF-β alone and unsupplemented controls. TGF-β-induced collagen-I production was downregulated significantly with the addition of mannose-6-phosphate in a dose-dependent manner in all 3 cells cultures. The mannose-6-phosphate also reduced TGF-β bioactivity. The study shows that mannose-6-phosphate was effective in TGF-β inhibition in cultured flexor tendon cells. The findings presented here encourage further experiments that use the agents to modulate TGF-β levels and reduce adhesion formation after flexor tendon repair.
Department of Orthopedics, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China. xcs009@ 163.com
Chang-suo
CS
Xia
Xuan-ying
XY
Yang
Wang
W
Yingzhen
Kang
K
Sun
Shaoqi
S
Tian
D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D008360:Mannosephosphates / Q000494:pharmacology*; D011817:Rabbits; D013710:Tendons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D024042:Collagen Type I; D008360:Mannosephosphates; D016212:Transforming Growth Factor beta; C027693:mannose-6-phosphate