The effect of surface immobilized NBD peptide on osteoclastogenesis of rough titanium plates in vitro and osseointegration of rough titanium implants in ovariectomized rats in vivo.

The effect of surface immobilized NBD peptide on osteoclastogenesis of rough titanium plates in vitro and osseointegration of rough titanium implants in ovariectomized rats in vivo.
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表面固定化NBD肽对粗钛板体外破骨细胞生成及体内去势大鼠粗钛种植体骨整合的影响

DOI:
10.1039/c8ra03116a
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发表时间:
2018-06-19
期刊:
影响因子:
3.9
通讯作者:
Xie, Zhijian
Xie, Zhijian
中科院分区:
化学3区
文献类型:
--
作者:
Wang, Yu;Zhang, Chen;Xu, Weijian;Wang, Baixiang;Lan, Yanhua;Yu, Mengfei;Wang, Pinger;Xie, Zhijian

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牙种植体成功的骨整合依赖于破骨细胞和成骨细胞的平衡激活。骨质疏松可上调破骨细胞活性,因此在这种情况下,需要找到有效的干预措施来抑制破骨细胞的生成并增强种植体的骨整合。据报道,NF-κB必需调节因子(NEMO)结合域(NBD)肽可以阻止破骨细胞的形成和骨吸收。在这项研究中,我们采用逐层技术将NBD肽偶联到粗糙的纯钛(Ti)表面。我们分析了表面特征,并通过细小颗粒结构的存在、S元素的增加和亲水性来确定NBD的成功整合。重要的是,我们首次报道了钛表面结合的NBD肽通过减少破骨细胞密封区的形成和功能来保留其对破骨细胞发生的抑制作用。这些作用是通过NFATc1表达的减少介导的,NFATc1通过靶向P65信号通路调节整合素ανβ3和MMP9。体内TRAP染色显示nbd涂层减少破骨细胞形成,假足减少。显微ct和组织形态学分析表明,nbd涂层显著增强了去卵巢大鼠体内骨整合。本研究为固定化NBD肽在体内的应用提供了广阔的前景,并为选择更合适的ti -种植体表面修饰以改善骨质疏松患者种植体骨整合提供了有效的治疗途径。
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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