In vitro analysis of the effect of Flightless i on murine tenocyte cellular functions

Abstract

Background: Healing of tendons after injury involves the proliferation of tenocytes and the production of extracellular matrix; however, their capacity to heal is limited by poor cell density and limited growth factor activity. Flightless I (Flii) has previously been identified as an important regulator of cellular proliferation and migration, and the purpose of this study was to evaluate the effect of differential Flii gene expression on tenocyte function in vitro. Methods: The role of Flii on tenocyte proliferation, migration, and contraction was assessed using established assays. Tenocytes from Flii +/-, wild-type, and Flii overexpressing mice were obtained and the effect of differential Flii expression on migration, proliferation, contraction, and collagen synthesis determined in vitro. Statistical differences were determined using unpaired Student's t test and statistical outliers were identified using the Grubbs' test. Results: Flii overexpressing tenocytes showed significantly improved migration and proliferation as well as increased collagen I secretion. Explanted tendons from Flii overexpressing mice also showed significantly elevated tenocyte outgrowth compared to Flii +/- mice. In contrast to its role in dermal wound repair, Flii positively affects cellular processes in tendons. Conclusions: These findings suggest that Flii could be a novel target for modulating tenocyte activity and improving tendon repair. This could have significant clinical implications as novel therapeutic targets for improved healing of tendon injuries are urgently needed.