Successful osseointegration in dental implants depends on balanced activation of osteoclasts and osteoblasts. Osteoporosis up-regulates osteoclast activity, so it is desirable to find effective interventions to inhibit osteoclastogenesis and enhance the osseointegration of implants under these conditions. It has been reported that the NF-κB essential modulator (NEMO)-binding domain (NBD) peptide can prevent osteoclast formation and bone resorption. In this study, we conjugated NBD peptide onto the surface of rough pure titanium (Ti) using the layer by layer technique. We analyzed the surface characteristics and determined the successful NBD integration by the presence of trivial granular structures, increased S elements and hydrophilia. Importantly, we first reported that Ti surface-conjugated NBD peptide retained its inhibitory effects on osteoclastogenesis by reducing osteoclast sealing zone formation and function. These effects were mediated by a reduction in NFATc1 expression, which in turn regulated integrin ανβ3 and MMP9 by targeting the P65 signaling pathway. In vivo TRAP staining suggested NBD-coating decreased osteoclast formation with less pseudopodia. Micro-CT and histomorphometric analysis demonstrated that NBD-coating enhanced pronounced osseointegration in vivo in ovariectomized rats. This study holds great promise for in vivo use of immobilized NBD peptide and offers an effective therapeutic approach to select more suitable Ti-implant surface modifications for improving implant osseointegration in osteoporotic patients.
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