Endothelial Progenitor Cells Enhance Bone Marrow-derived Macrophages Migration And Osteoclastogenesis In Vitro Via Talin-1

Background and Objectives:Bone resorption mediated by osteoclasts plays an important role in bone healing.Endothelial progenitor cells(EPCs)promote bone repair by stimulating neovascularization and osteogenesis.However,the role of EPCs in osteoclast formation and function is not well defined.The aim of this study was to elucidate mechanisms of EPCs in osteoclast formation and functions.Methods:In this study,we examined the effects of EPCs on the proliferation,migration and osteoclastogenesis of primary mouse bone marrow-derived macrophages(BMMs)in a co-culture system in vitro.We evaluated the effects of EPCs co-transplantation on the homing and osteoclastogenesis of transplanted BMMs in a mouse bone fracture model in vivo.The technology of immunofluorescence,immunohistochemical,western blot,Rt-PCR,cell co-culture and transwell were used in this study.Results:EPCs secreted TGF-?1 in the EPC-BMM co-culture medium and increased Talin-1 expression in the co-cultured BMMs.Treatment with a TGF-?1 neutralizing antibody or Talin-1 silencing in BMMs completely inhibited BMM osteoclastic differentiation in the co-culture system.These results indicated that the osteoclastogenic effects of EPCs were mediated by TGF-?1-mediated Talin-1 expression in BMMs.In the femur fracture model,BMMs co-transplanted with EPCs exhibited enhanced engraftment into the fracture site and osteoclastic differentiation compared with those transplanted alone.Mice treated with EPC-BMM co-transplantation exhibited increased neovascularization at the fracture site and accelerated fracture healing compared with those treated with BMMs alone.Conclusion:Taken together,the results suggest that EPCs can promote bone repair by enhancing recruitment and differentiation of osteoclast precursors.