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

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

Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery (2019-01-09)
Sevinç Kenan, Özen Doğan Onur, Seyhun Solakoğlu, Tuğba Kotil, Mustafa Ramazanoğlu, Hakan Hamdi Çelik, Mert Ocak, Bora Uzuner, Erhan Fıratlı
ABSTRACT

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.