In Vitro Flexor Tendon Cell Response to TGF-β1: A Gene Expression Study

Purpose Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-beta 1 (TGF-beta 1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation. Methods Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-beta 1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAL-1), and tissue plasminogen activator (t-PA). Results Endotenon-derived cells showed a statistically significant down-regulation of collagen type 1 gene expression in response to TGF-beta 1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase. Conclusions We have shown that cells cultured from 3 separate parts of the flexor tendon-sheath complex respond in different ways when stimulated with TGF-beta 1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-beta 1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-beta 1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-beta 1. (J Hand Surg 2009;34A:495-503. Copyright (C) 2009 by the American Society for Surgery of the Hand. All rights reserved.)