Local treatment with Sema3a could promote the osseointegration of hydroxyapatite coated titanium rod in diabetic rats

Recently, semaphorin 3A (Sema3A) has been identified as a critical gene for osteogenic differentiation of mesenchymal stem cells and increases osteoblastic bone formation. However, in current research studies, there is a lack of focus on whether Sema3a can affect the osseointegration of titanium rods in diabetes and through what biological mechanisms. Therefore, the present work was aimed to evaluate the effect of local administration with Sema3A on hydroxyapatite coated titanium rod osseointegration in diabetic rat model and preliminary exploration of possible mechanisms. The MC3T3-E1 cells were co-cultured with Sema3A and high glucose and induced to osteogenesis, and the cell viability, osteogenic activity was observed by Cell Counting Kit-8(CCK-8), Alkaline Phosphatase staining, Alizarin Red Staining, and Western Blot. In vitro experiments, CCK-8, ALP, and ARS staining results show that the mineralization and osteogenic activity of MC3T3-E1increased significantly after intervention by Sema3A, as well as a higher levels of protein expressions including Runt-Related Transcription Factor 2, silent mating type information regulation 2 homolog-1(SIRT1), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). In vivo experiment, a better stability and osseointegration of the titanium rod were observed after treatment with Sema3A, as well as a higher SOD1, SOD2, CAT, and SIRT1 gene expression. The present study indicates that local treatment with Sema3A was associated with increased osseointegration of titanium rod by reducing the oxidative stress of osteoblasts and enhancing the function of osteoblasts in a diabetic rat.