Adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath results in a decreased postoperative range of motion (ROM) 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 TGF-β1 neutralizing antibody were investigated in vitro and in vivo. 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 TGF-β1 neutralizing antibody. Collagen I production was measured with enzyme-linked immunosorbent assay. In the in vivo study, rabbit zone-II flexor tendons were transected and then immediately repaired. Transforming growth factor-β1 neutralizing antibody or phosphate-buffered saline solution (control) was added to the repair sites, and the forepaws were tested for ROM and repair strength at 8 weeks postoperatively. Transforming growth factor-β1 neutralizing antibody reduced TGF-β upregulated collagen production. Intraoperative application of TGF-β1 neutralizing antibody significantly improved the ROM of the operatively treated digits. The effect on breaking strength of the tendon repair was inconclusive.

Recent studies have shown the importance of transforming growth factor-beta (TGF-beta) in flexor tendon wound healing. Decreased adhesion formation and increased range of motion after the administration of TGF-beta antibodies after tendon repair have been shown. But TGF-beta antibodies have a short biologic half-life, and continuous supplementation of exogenous TGF-beta antibodies is not practical. Transfer of growth factor genes to tenocytes provides an alternative to protein therapeutics, and a gene therapy approach will prolong the availability of therapeutic proteins.We investigated the biological activities effects of rabbit tendon sheath fibroblasts transfected by antisense TGF-beta1 gene. Tendon sheath fibroblasts were isolated from New Zealand white rabbits and transfected by antisense TGF-beta1 gene with Lipofectin (Invitrogen, Carlsbad, California). Reverse transcription polymerase chain reaction was used to measure collagen I, collagen III, and TGF-beta1 expression, and Western blot was used to measure collagen protein I expression in tendon sheath fibroblasts after being transfected by antisense TGF-beta1 gene. Reverse transcription polymerase chain reaction displayed that tendon sheath fibroblasts transfected with antisense TGF-beta1 gene showed marked decrease collagen I, collagen III, and TGF-beta1 mRNA expression. Western blot showed that tendon sheath fibroblasts transfected with antisense TGF-beta1 gene showed marked decrease expression of collagen I protein, and there was significant difference compared with the untransfected and empty transfected groups (P<.01). Tendon sheath fibroblasts can transfect with antisense TGF-beta1 gene successfully and can decrease production of collagen I, collagen III, and TGF-beta1, which were factors of tendon adhere formation.