Bidirectional EphrinB2/ephB4 Signaling Intercellular Communication Mechanism In Particle-induced Bone Remolding Imbalance

Back ground/Aim: Aseptic loosening around the prosthesis caused by wear particles is one of the common complications after total hip arthroplasty.The present study investigated the role of the recombinant protein eph B4-Fc(erythropoietin-producing human hepatocellular receptor 4)in the regulation of wear particle-mediated osteolysis and inflammatory response.Methods: We study the ephrin B2 expression though the intervention of small interfering RNA-N fatc1 and small interfering RNA-c-Fos.We also used TRAP staining,F-actin formation,bone pit resorption,ELISA experiments,and ephrin B2over-expression and knockdown experiments to verify that the addition of eph B4-Fc can inhibit the maturation of osteoclasts in vitro.Further,a mouse skull model was constructed to verify that eph B4-Fc can inhibit osteolysis and inhibit inflammation in vivo.Results: We have found that the expression of ephr in B2 receptor on mouse bone marrow macrophages(BMMs)in the presence of titanium particles is up-regulated.And the ephrin B2 expression was down-regulated by si RNA.TRAP staining,F-action formation,bone pit resorption was inhibited.This phenomenon has also been confirmed by the over-expression and knockdown of the ephrin B2 expression.More importantly,we found that when added to the eph B4-Fc recombinant protein,inflammatory cytokines mediated by titanium wear particles were inhibited by ELISA.We also obtained experimental results similar to in vitro experiments by micro-CT,H&E staining,immunohistochemistry,and immunofluorescence experiments on the mouse skull.Conclusion: Recombinant protein eph B4-Fc can inhibit wear particle-mediated osteolysis and inflammatory response through the ephrin B2/eph B4 bidirectional signaling pathway,and ephrin B2 ligand is expected to become a new clinical drug therapeutic target.