Abstract：
Peri-implantitis is characterized by inflammatory cell infiltration and hyperactivation of the osteoclasts surrounding dental implants which can result in bone resorption and ultimately implant failure. Therefore, coordinating the activity of inflammatory response and bone-resorbing osteoclasts is crucial for the prevention of peri-implantitis. Asperuloside (ASP), an iridoid glycoside, has significant anti-inflammatory activities, suggesting the great potential in attenuating peri-implantitis bone resorption. A ligature-induced peri-implantitis model in the maxilla of rats was established, and the effects of ASP on preventing peri-implantitis were evaluated after four weeks of ligation using micro-CT and histological staining. RT-PCR, western blotting, tartrate-resistant acid phosphatase (TRAP), and immunofluorescent staining were conducted on osteoclasts to confirm the mechanisms of ASP on osteoclastogenesis. The results show that ASP could lead to attenuation of alveolar bone resorption in peri-implantitis by inhibiting osteoclast formation and decreasing pro-inflammatory cytokine levels in vivo. Furthermore, ASP could inhibit osteoclastogenesis by downregulating expression levels of transcription factors nuclear factor of activated T-cell (NFATc1) via restraining the activations of nuclear factor kappa beta (NF-κB) and the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2). In conclusion, ASP could significantly attenuate bone resorption in peri-implantitis via inhibition of osteoclastogenesis by suppressing NF-κB and ERK1/2 signaling pathways activations.
摘要：
种植体周围炎的特征在于牙科植入物周围的破骨细胞的炎性细胞浸润和过度活化,这可导致骨吸收并最终导致植入物失败。因此,协调炎症反应和骨吸收破骨细胞的活性对于预防种植体周围炎至关重要.Asperuloside（ASP），一种环烯醚萜苷,具有显著的抗炎活性，提示在减轻种植体周围炎骨吸收方面的巨大潜力。建立大鼠上颌骨结扎诱发种植体周围炎模型,结扎四周后，使用micro-CT和组织学染色评估ASP预防种植体周围炎的效果。RT-PCR,西方印迹,抗酒石酸酸性磷酸酶（TRAP），对破骨细胞进行免疫荧光染色，以证实ASP对破骨细胞生成的作用机制。结果表明，ASP可以通过抑制破骨细胞形成和降低体内促炎细胞因子水平，从而减轻种植体周围炎的牙槽骨吸收。此外，ASP通过抑制核因子κβ（NF-κB）的激活和细胞外信号相关激酶1/2（ERK1/2）的磷酸化，下调转录因子活化T细胞核因子（NFATc1）的表达水平，从而抑制破骨细胞的生成。总之,ASP可以通过抑制NF-κB和ERK1/2信号通路的激活来抑制破骨细胞的生成，从而显著减弱种植体周炎的骨吸收。
