The effect of semaphorin 3A on fracture healing in osteoporotic rats.

Abstract

Semaphorin 3A (Sema3A) was demonstrated to exert an osteoprotective effect by both inhibiting osteoclastic bone resorption and promoting osteoblastic bone formation. The effect of Sema3A on fracture healing of osteoporotic rats was investigated in this study. Twelve weeks after bilateral ovariectomy, all animals underwent unilateral transverse osteotomy on the proximal tibiae, and were then randomly divided into two groups. Rats received vehicle (control) or weekly local injection of Sema3A (500 μg/kg) into the injury site (group Sema3A) after fracture surgery until sacrifice at 4 and 8 weeks. Specimens were harvested and examined by radiography, iDXA, histology, micro-CT, and three-point bending test. Compared to control, Sema3A treatment significantly increased bone mineral density, percent bone volume and biomechanical strength of the callus at 4 and 8 weeks post-fracture. At 8 weeks after fracture, the bone volume of callus showed no difference between groups, while the average cross-sectional area of callus in the control group was 43.8 % higher than that of Sema3A group. Histological images showed increased callus formation at 4 weeks post-fracture and better callus ossification in the Sema3A group, while callus remodeling in the control group seemed to be delayed and not well bridged. Results in this study indicated that Sema3A treatment increased callus volume and density at 4 weeks post-fracture, and induced promoted callus ossification and remodeling at 8 weeks post-fracture compared to control.