Wang Yu, Zhang Chen, Xu Weijian, Wang Baixiang, Lan Yanhua, Yu Mengfei, Wang Pinger, Xie Zhijian
Department of Implantology, Affiliated Hospital of Stomatology, Medical College, Zhejiang University Hangzhou P. R. China.
Department of Oral Medicine, Affiliated Hospital of Stomatology, Medical College, Zhejiang University Hangzhou P. R. China.
RSC Adv. 2018 Jun 21;8(40):22853-22865. doi: 10.1039/c8ra03116a. eCollection 2018 Jun 19.
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 ανβ and MMP9 by targeting the P65 signaling pathway. TRAP staining suggested NBD-coating decreased osteoclast formation with less pseudopodia. Micro-CT and histomorphometric analysis demonstrated that NBD-coating enhanced pronounced osseointegration in ovariectomized rats. This study holds great promise for 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.
牙种植体的成功骨整合取决于破骨细胞和成骨细胞的平衡激活。骨质疏松症会上调破骨细胞活性,因此需要找到有效的干预措施来抑制破骨细胞生成,并在这些情况下增强种植体的骨整合。据报道,核因子κB必需调节因子(NEMO)结合域(NBD)肽可防止破骨细胞形成和骨吸收。在本研究中,我们使用层层技术将NBD肽偶联到粗糙纯钛(Ti)表面。我们分析了表面特性,并通过微小颗粒结构的存在、S元素增加和亲水性确定了NBD的成功整合。重要的是,我们首次报道,Ti表面偶联的NBD肽通过减少破骨细胞封闭区的形成和功能,保留了其对破骨细胞生成的抑制作用。这些作用是由NFATc1表达的降低介导的,而NFATc1表达的降低又通过靶向P65信号通路调节整合素ανβ和MMP9。抗酒石酸酸性磷酸酶(TRAP)染色表明,NBD涂层减少了破骨细胞的形成,伪足也较少。显微CT和组织形态计量学分析表明,NBD涂层增强了去卵巢大鼠的骨整合。这项研究为固定化NBD肽的应用带来了巨大希望,并提供了一种有效的治疗方法,以选择更合适的Ti种植体表面改性,从而改善骨质疏松患者的种植体骨整合。