In vivo gene transfer and overexpression of focal adhesion kinase (pp125 FAK) mediated by recombinant adenovirus-induced tendon adhesion formation and epitenon cell change.

Abstract

Adhesion formation is a frequent complication of tendon injury repair: however, little is known about its mechanisms. The intracellular focal adhesion kinase (FAK)-related signaling pathway may be one of the mechanisms involved in the induction of tendon adhesions. The replication deficient adenovirus containing the FAK gene (pp125 FAK) was constructed and named Adv-Fak. By in vitro transductions with the recombinant virus, overexpression of the FAK protein was documented in transduced cultured primary tendon cells. By in vivo direct injection of Adv-FAK into the space between the tendon and tendon sheath of White Leghorn chickens, FAK gene transfer with overexpression of the FAK protein was detected by immunohistological staining. The morphology of these stained cells changed from the normal flat shape to cuboid. The group with overexpressed adenovirus-mediated FAK had significant adhesion formation, as seen by increased work of flexion (118.197 +/- 29.616), compared with the group with overexpressed adenovirus-mediated beta-galactosidase (67.507 +/- 36.066) (p < 0.0393) and the group with adenovirus-mediated FAK antisense gene transfer (60.357 +/- 48.562) (p < 0.0211). Histological examination of the samples from tendons with Adv-FAK showed fibers between the tendon and tendon sheath; there were no fibers in the cavities of samples of injured tendons infected with Adv-beta gal. Moreover, at the application site of the former tendons, a thick fiber layer without epitenon cells was built up on the outer surface, whereas a thin fiber layer with clear epitenon cells was observed in the tendons to which Adv-beta gal was applied. Our results show that overexpression of FAK can induce tendon adhesion formation in vivo. This indicates that FAK and the FAK-related signaling pathway may be involved in the process of tendon adhesion formation. Understanding the details of this process may help to prevent tendon adhesion and improve healing.