Mechanism of intracellular signaling transduction through p-catenin during fracture healing

Abstract

Objective To observe the changes of p-catenin during fracture repair and explore the mechanism of signaling transduction through p-catenin during fracture repair. Methods Mice were randomly divided into three groups,and the animal models of tibia fracture were established. Western blot analysis was employed for detecting the p-catenin expression at different time points during fracture repair. Quantitative RT-PCR was used to detect Wnt ligmants and their receptors during fracture repair to understand whether signaling transduction through p-catenin during fracture healing was directly regulated by Wnts. Histomorphometric measurements were used to observe the effect of Dkk-1 on fracture repair for further understanding function of p-catenin. Results p-catenin level was low in intact bone tissue,but highly expressed during the entire period of fracture repair. Callus samples from animals treated with Ad-Dkkl exhibited a greater reduction of β-catenin level. Wnt-4, Wnt5b and their receptors Fz-1 and Lrp-6 were upregulated during fracture healing. In Dkk-1 and contror groups, using histomorphometric measurements, there was substantial reduction of callus parameters. Bone and cartilage volume as a percentage of total callus tissue volume,trabecular thickness,trabecular number (per mm) and trabecular separation (μm) in Dkk-1 and contror groups were (11.33 ± 2. 52)%/(35. 67 ± 3.06)% , (14. 33 ± 2 51)%/(47. 33 ± 4.04)%,(720.00 ±77.70) μm/(189.33 ±83.36)μm,13.67 ±2.05/32.33 ±2.62,(1.25 ±0.96) μm/ (4.00 ± 0.82) ujn respectively (P<0.01). Conclusion p-catenin may play a key signaling role during fracture healing. The therapy to activate p-catenin could be used to enhance fracture repair. Key words: Fracture healing; p-catenin; Wnts; Signaling transduction