Gene expression of transforming growth factor beta-1 in rabbit zone II flexor tendon wound healing: evidence for dual mechanisms of repair

Abstract

The postoperative outcome of hand flexor tendon repair can be complicated by adhesions between the repair site and surrounding tissue. To date, the biology of hand flexor tendon wound healing remains controversial--both intrinsic (resident tenocyte) and extrinsic (tendon sheath fibroblast and inflammatory cell) processes may contribute to repair. Transforming growth factor beta-1 is a cytokine that plays multiple roles in wound healing but is also implicated in the pathogenesis of excessive scar formation. This study examines the activation of transforming growth factor beta-1 mRNA in a rabbit zone II flexor tendon wound-healing model. Forty New Zealand White rabbit forepaws underwent complete transection and repair of the middle digit flexor digitorum profundus tendon in zone II. Tendons were harvested at increasing time intervals (1, 3, 7, 14, 28, and 56 days) and analyzed by in situ hybridization and immunohistochemistry to determine the expression patterns of transforming growth factor beta-1. A small number of tenocytes exhibited expression of transforming growth factor beta-1 mRNA at baseline in nonwounded control tendon specimens. The surrounding tendon sheath in these control specimens also revealed low numbers of fibroblasts and inflammatory cells expressing transforming growth factor beta-1 mRNA. In contrast, flexor tendons subjected to transection and repair exhibited increased signal for transforming growth factor beta-1 mRNA in both resident tenocytes and infiltrating fibroblasts and inflammatory cells from the tendon sheath. These data demonstrate that (1) normal unwounded tenocytes and tendon sheath cells are capable of transforming growth factor beta-1 production, (2) this cytokine is activated in the tendon wound environment, as evidenced by mRNA upregulation, and (3) the upregulation of this cytokine in both "intrinsic" tenocytes and "extrinsic" tendon sheath fibroblasts and inflammatory cells supports dual mechanisms for tendon repair. Because transforming growth factor beta-1 is thought to contribute to the pathogenesis of excessive scar formation, the findings presented here suggest that perioperative biochemical modulation of transforming growth factor beta-1 levels may help limit flexor tendon adhesion formation.