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

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 microCT 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.