Introduction Post-operative adhesions frequently compromise the success of flexor tendon repair. TGF-beta is a key cytokine in the pathogenesis of tissue fibrosis. We examined the effectiveness of TGF-beta neutralizing antibody (neu-Ab) and two natural inhibitors-decorin and mannose-6-phosphate (M6P)-in blocking TGF-beta induced collagen I (Col I) production in cultured flexor tendon cells.

Methods Three separate cell cutures-sheath fibroblasts (S), epitenon tenocytes (E), and endotenon tenocytes (T)-were obtained from rabbit flexor tendons. Each cell culture was supplemented with TGF-beta (1ng/ml) along with increasing doses of neu-Ab, decorin or M6P. Col I production was measured by ELISA. Results were compared to TGF-beta only and non-supplemented controls. All studies were triplicated.

Results Addition of neu-Ab significantly reduced TGF-beta-induced Col I production in a dose-dependent manner in all 3 cell cultures. At the highest dose of neu-Ab tested (2 mg/ml), Col I production was reduced by 68%, 61%, and 26% in S, E, and T cells. Decorin and M6P also reduced TGF-beta-induced Col I production. At the highest concentration of decorin tested (50 nmol), Col I production was reduced by 38% and 44% in S and E cells. At the highest concentration of M6P tested (100 mumol), Col I production was reduced by 76%, 64%, and 29% in S, E, and T cells respectively.

Conclusions A biochemical method of reducing scar formation could help minimize the sequelae of flexor tendon adhesions. This model is the initial step towards the identification of anti-scarring agents that may modulate flexor tendon wound healing. Anti-TGF- b therapy in flexor tendon wound healing will have direct applications in flexor tendon repair and will also serve as a model for minimizing scar formation in other tissues.
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