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抗菌肽GL13K修饰的钛通过H3K27me3对破骨细胞分化进行表观遗传调控。

Antimicrobial peptide GL13K-Modified titanium in the epigenetic regulation of osteoclast differentiation via H3K27me3.

作者信息

Gao Yuerong, Lai Yingzhen, Wang Hong, Su Jingjing, Chen Yan, Mao ShunJie, Guan Xin, Cai Yihuang, Chen Jiang

机构信息

School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China.

Department of Stomatology, Engineering Research Center of Fujian University for Stomatological Biomaterials, Xiamen Medical College, Xiamen, Fujian, China.

出版信息

Front Bioeng Biotechnol. 2024 Oct 24;12:1497265. doi: 10.3389/fbioe.2024.1497265. eCollection 2024.

Abstract

Implant surface designs have advanced to address challenges in oral rehabilitation for healthy and compromised bone. Several studies have analyzed the effects of altering material surfaces on osteogenic differentiation. However, the crucial role of osteoclasts in osseointegration has often been overlooked. Overactive osteoclasts can compromise implant stability. In this study, we employed a silanization method to alter pure titanium to produce a surface loaded with the antimicrobial peptide GL13K that enhanced biocompatibility. Pure titanium (Ti), silanization-modified titanium, and GL13K-modified titanium (GL13K-Ti) were co-cultured with macrophages. Our findings indicated that GL13K-Ti partially inhibited osteoclastogenesis and expression of osteoclast-related genes and proteins by limiting the formation of the actin ring, an important structure for osteoclast bone resorption. Our subsequent experiments confirmed the epigenetic role in regulating this process. GL13K-Ti was found to impact the degree of methylation modifications of H3K27 in the promoter region following RANKL-induced osteoclastic differentiation. In conclusion, our study unveils the potential mechanism of methylation modifications, a type of epigenetic regulatory modality, on osteoclastogenesis and activity on the surface of a material. This presents novel concepts and ideas for further broadening the clinical indications of oral implants and targeting the design of implant surfaces.

摘要

种植体表面设计已经取得进展,以应对健康和受损骨组织口腔修复中的挑战。多项研究分析了改变材料表面对成骨细胞分化的影响。然而,破骨细胞在骨整合中的关键作用常常被忽视。破骨细胞过度活跃会损害种植体稳定性。在本研究中,我们采用硅烷化方法对纯钛进行改性,以制备负载抗菌肽GL13K的表面,从而增强生物相容性。将纯钛(Ti)、硅烷化改性钛和GL13K改性钛(GL13K-Ti)与巨噬细胞共培养。我们的研究结果表明,GL13K-Ti通过限制肌动蛋白环(破骨细胞骨吸收的重要结构)的形成,部分抑制破骨细胞生成以及破骨细胞相关基因和蛋白的表达。我们随后的实验证实了表观遗传学在调节这一过程中的作用。研究发现,GL13K-Ti在RANKL诱导破骨细胞分化后,会影响启动子区域H3K27的甲基化修饰程度。总之,我们的研究揭示了甲基化修饰(一种表观遗传调控方式)对材料表面破骨细胞生成和活性的潜在作用机制。这为进一步拓宽口腔种植体的临床适应证以及靶向种植体表面设计提供了新的概念和思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4779/11540686/37bce8840b78/fbioe-12-1497265-g001.jpg

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