Investigation of the effects of semaphorin 3A on new bone formation in a rat calvarial defect model.

This study investigates the effects of semaphorin 3A on new bone formation in an experimental rat model. Cortical bone defects, 5 mm, were created in the calvaria of 40 Wistar rats, which were then separated into three groups: empty defect (control) group, collagen group, collagen + semaphorin 3A group. The bone blocks were harvested after 4 and 8 weeks. New bone formation was assessed by micro-computed tomography (micro-CT), histology, histomorphometry, transmission electron microscope (TEM) and immunohistochemistry. Increased bone formation was observed in collagen + semaphorin 3A groups both histologically and with micro-CT. In the histomorphometic analysis, the control group had significantly less bone formation compared to both the collagen and collagen + semaphorin 3A group at 4 weeks (p = 0.0001) and 8 weeks (p = 0.0001). The collagen group had significantly less bone formation compared to collagen + semaphorin 3A group both at 4 weeks (p = 0.002) and 8 weeks (p = 0.005). Immunohistochemical analysis revealed that semaphorin 3A inhibited receptor activator of nuclear factor-kB ligand (RANKL) expression and increased the expressions of osteoblastic bone markers at 4 weeks. In TEM analysis, the collagen + semaphorin 3A group had an increased proliferation and bone formation rate at 4 weeks, whereas bone quantity and maturation were enhanced at 8 weeks. Locally applied semaphorin 3A increases callus formation at 4 weeks and bone formation at 8 weeks. Semaphorin 3A prevents bone resorption by inhibiting osteoclasts and increases bone formation by inducing osteoblasts.