ED-71 promotes osseointegration of titanium implants in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner

IF 2.6 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of Oral Biosciences Pub Date : 2025-03-01 DOI:10.1016/j.job.2024.10.003

Chunying Li , Pengfei Xue , Guanglin Duan , Ailing Song , Runbing Zhai , Jie Ma , Minqi Li

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Abstract

Objective

Glucocorticoid-induced osteoporosis (GIOP), a common complication of glucocorticoid usage, plays a critical role in the success of dental implant restoration by affecting osseointegration. Eldecalcitol (ED-71) prevents GIOP; however, its role in the osseointegration of implants under GIOP conditions remains elusive.

Methods

Dexamethasone was used to establish a rat model of GIOP. Subsequently, mini-implant surgery was performed on the femur. GIOP rats were administered ED-71 via gavage to assess its role in the osseointegration of titanium implants under GIOP conditions. MC3T3-E1 and RAW264.7 cells were utilized to explore the molecular mechanism of ED-71 in ameliorating disorder of bone remodeling caused by dexamethasone.

Results

The administration of ED-71 promoted the formation of newly formed woven bone and the resolution of inflammation around titanium implants. In vitro experiments indicated that ED-71 ameliorated dexamethasone-induced dysfunction of osteoblasts and osteoclasts by increasing the expression level of sirtuin 1 (SIRT1). Inhibition of SIRT1 by selisistat counteracts the regulatory effects of ED-71 on dexamethasone-induced disorder of bone remodeling. Molecular docking and Western blotting revealed that the neurogenic locus notch homolog protein and nuclear factor kappa B signaling pathways are essential for the effects of ED-71 on dexamethasone-induced disorder of bone remodeling.

Conclusion

ED-71 promoted implant osseointegration in a rat model of GIOP by alleviating the effects of dexamethasone on bone remodeling in a SIRT1-dependent manner.

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ED-71 可通过 SIRT1 依赖性方式减轻地塞米松对骨重塑的影响，从而促进钛植入物在大鼠 GIOP 模型中的骨结合。

目的：糖皮质激素诱导的骨质疏松症（GIOP）是使用糖皮质激素的常见并发症，它通过影响骨结合对牙科种植修复的成功起着至关重要的作用。艾地卡骨化醇（ED-71）可预防 GIOP，但它在 GIOP 条件下对种植体骨结合的作用仍不明确：方法：使用地塞米松建立大鼠 GIOP 模型。方法：使用地塞米松建立 GIOP 大鼠模型，随后在股骨上进行微型植入手术。给 GIOP 大鼠灌胃 ED-71，以评估其在 GIOP 条件下对钛植入物骨结合的作用。利用 MC3T3-E1 和 RAW264.7 细胞探讨 ED-71 改善地塞米松引起的骨重塑紊乱的分子机制：结果：服用ED-71可促进新形成的编织骨的形成，并缓解钛种植体周围的炎症。体外实验表明，ED-71通过提高sirtuin 1（SIRT1）的表达水平，改善了地塞米松诱导的成骨细胞和破骨细胞功能障碍。塞利司他对SIRT1的抑制抵消了ED-71对地塞米松诱导的骨重塑障碍的调节作用。分子对接和Western印迹显示，ED-71对地塞米松诱导的骨重塑障碍的影响离不开神经原位点缺口同源蛋白和核因子卡巴B信号通路：结论：ED-71以SIRT1依赖的方式减轻了地塞米松对骨重塑的影响，从而促进了大鼠GIOP模型中种植体的骨结合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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