Inhibition of TGF-β-Induced Collagen Production in Rabbit Flexor Tendon with Mannose-6-Phosphate in Vitro

Abstract

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.