Sema3A Promotes The Repair Of Jaw Defects By Regulating The Proliferation And Osteogenic Differentiation Of Mesenchymal Stem Cells

Part ?Effect of Sema3 A on Biological Behavior of BMSCs Obiective: Bone regeneration is a complex process involving many growth factors and cells.Mesenchymal stem cells possess multi-potential diferentiation and can be recruited to damaged sites to differentiate into osteogenic cells,which play key roles in bone repair.Recently,it reported that Sema3 A can promote bone formation and inhibit bone resorption,however,the effect of Sema3 A on BMSCs is still unclear.The purpose of this study is to observe the influence of Sema3 A on BMSCs to explore the role of Sema3 A in bone regeneration.Methods: BMSCs were isolated from bone marrow of mice.Cell viability and apoptosis of mouse-derived BMSCs were examined by MTS and FCM.The effect of Sema3 A on osteogenic differentiation of BMSCs were assessed with Realtime-PCR.Result: Sema3 A stimulated cell viability and decreased cell apoptosis of BMSCs.At day 7,Sema3 A significantly elevated the expression of osteogenic-related genes,including Runt-related transcription factor 2(RUNX2),type I collagen(ColI)and Osteocalcin(OCN)compared with control group.A significant upregulation of OCN at day 14 and alkaline phosphatase(ALP),Runx2 and ColI at day 21 were also observed in the Sema3 A group compared to control group.Conclusions: Sema3 A could increase the viability of BMSCs and induce the transformation of BMSCs into osteoblasts at the early and late stage of differentiation.This suggested that Sema3 A might accelerate the bone regeneration by promoting osteogenic differentiation of BMSCs.Part? The impact of Sema3 A on regeneration of jaw defectsObiective: Reconstruction of jaw defects due to trauma,tumors,dysplasia has always been a challenge in stomatology.For bone repair,a variety of cytokines play an important role through autocrine and paracrine.Recent studies have shown that Sema3 A not only promotes osteogenic differentiation of cells such as adipose mesenchymal stem cells,but also inhibits the formation of osteoclasts,suggesting that it might be used as an effective factor to promote bone formation in vivo.In this study,Bio-Gide~@collagen membrane carried with Sema3 A was used to repair the mandibular defects,the effects of Sema3 A on mandibular regeneration were explored.Methods: 36 mice were randomly divided into control group,CM group and Sema3A+CM group(six in each group).A bone defect with a diameter of 1.5 mm and a depth of 1 mm was fabricated under the first mandibular molar of the mouse using a dental drill.The control group was left empty,the CM group was implanted with a 1.5 mm diameter Bio-Gide~@ collagen membrane,and the Sema3 A group was implanted with a 1.5 mm diameter Bio-Gide~@ collagen membrane bearing 10 ng Sema3 A.The samples were collected at 1,2 and 4 weeks,respectively,and then subjected to Micro-CT and HE staining to analyze the bone healing.Result: In Sema3A+CM group,bone volume fraction(BV/TV),bone surface area(BS),bone surface area volume ratio(BS/TV),and number of trabecular bone(Tb.N)were significantly higher than that in CM and control group,and there was no difference between CM and control group.Furthermore,compared with CM and control group,HE staining analysis demonstrated the new bone formation was greater in Sema3 A group.However,trabecular thickness(Tb.Th)and trabecular separation(Tb.Sp)showed no difference in three groups(P>0.05).Conclusions: Sema3 A could promote the regeneration of jaw defects and has the potential to be applied in the bone repair.