Knee loading stimulates healing of mouse bone wounds in a femur neck

Abstract

Healing of bone wounds is sensitive to various environmental stimuli. Using knee loading, which has been shown to stimulate bone formation in mouse femora and tibiae, we addressed a question: Does knee loading accelerate a closure of open wounds in a femur neck? A surgical wound (0.5 mm in diameter) was generated at the femur neck in the left and right femora of C57/BL/6 female mice, and knee loading was applied to the left knee for 3 min/day for 3 consecutive days. Surgical holes at the femoral midshaft were used as control. Animals were sacrificed 1, 2, and 3 weeks after surgery for analyses with μCT and pQCT as well as mechanical testing. The results showed load-driven acceleration of the closure of surgical holes. Compared to a sham-loaded contralateral control, knee loading reduced the size of surgical wounds in the femoral midshaft by 14% (p<0.05), 21% (p<0.01), and 32% (p<0.001) in 1, 2, and 3 weeks, respectively. It also decreased the wound size in the femur neck by 16% (p<0.001; 1 week), 18% (p<0.001; 2 weeks), and 21% (p<0.001; 3 weeks). Images with pQCT revealed that bone mineral density (BMD) was increased from 571±19 mg/cm(3) (control) to 686±19 mg/cm(3) (loaded) (p<0.01), and bone mineral content (BMC) from 3.05±0.12 mg/mm (control) to 3.42±0.11 mg/mm (loaded) (p<0.05). Furthermore, mechanical testing showed that stiffness of the femur was increased by knee loading (p<0.05). This study demonstrates that knee loading is capable of accelerating healing of surgical wounds throughout the femur including the femoral midshaft and neck.