Tideglusib增强3D胶原支架内成骨-巨噬细胞共培养中ALP活性和上调RANKL表达

IF 4.8 2区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of dentistry Pub Date : 2025-02-01 DOI:10.1016/j.jdent.2024.105509

Raquel Toledano , María T. Osorio , Raquel Osorio , Manuel Toledano , Diego Jacho , Eda Yildirim-Ayan

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引用次数: 0

摘要

目的：Tideglusib （Tx）以其成骨潜能而闻名，但其对成骨细胞和M1巨噬细胞之间相互作用的影响仍未得到充分研究。本体外研究旨在分离和评估M1巨噬细胞和成骨细胞在巨噬细胞分化和成骨细胞功能中的单独和联合作用，特别关注这些相互作用如何影响成骨和破骨细胞生成的蛋白表达在存在或不存在tx的情况下。将成骨细胞和巨噬细胞直接接触共培养24和48小时，无论是否存在Tx. ALP活性，使用RT-qPCR检测炎症相关基因的表达，并进行组织学分析。结果：成骨细胞和M1巨噬细胞与Tx共培养可增加碱性磷酸酶的产生，表明成骨细胞活性增强。组织学评估显示，Tx处理有助于支架内细胞形态的稳定和维持，表明细胞活力和功能的支持环境。在共培养24和48 h时，Tx显著降低促炎标志物TNF-α和IL-1β的表达。Tx还能有效抑制巨噬细胞的破骨细胞分化，从而降低其促炎表型。结论：Tx增加ALP活性，显著上调RANKL表达，促进成骨细胞分化和破骨细胞活化。Tx减轻巨噬细胞驱动的炎症。临床意义：Tx可能通过调节炎症反应和保持细胞完整性来促进骨再生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Tideglusib enhances ALP activity and upregulates RANKL expression in Osteoblast-macrophage Co-cultures within a 3D collagen scaffold

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Tideglusib enhances ALP activity and upregulates RANKL expression in Osteoblast-macrophage Co-cultures within a 3D collagen scaffold

Objectives

Tideglusib (Tx) is known for its osteogenic potential, yet its effects on the interplay between osteoblasts and M1 macrophages remain underexplored. This in vitro study aimed to isolate and evaluate both the individual and combined roles of M1 macrophages and osteoblasts in macrophage differentiation and osteoblast function, specifically focusing on how these interactions influence protein expression of osteogenesis and osteoclastogenesis in the presence or absence of Tx.

Methods

Osteoblast and macrophage cells were co-cultured in direct contact for 24 and 48 h, with or without the presence of Tx. ALP activity, the expression of inflammatory-related genes using RT-qPCR, and histological analyses were performed.

Results

Co-culturing osteoblasts and M1 macrophages with Tx increased alkaline phosphatase production, indicative of enhanced osteoblast activity. Histological assessments revealed that Tx treatment contributed to the stability and maintenance of cell morphology within the scaffold, suggesting a supportive environment for cell viability and function. Tx significantly reduced the expression of pro-inflammatory markers, such as TNF-α and IL-1β, in the co-culture at both 24 and 48 h Tx also effectively inhibited osteoclastogenic differentiation in macrophages, thereby diminishing their pro-inflammatory phenotype.

Conclusions

Tx increased ALP activity and produced a significant up-regulation of RANKL expression, indicating enhanced osteoblast differentiation and osteoclast activation. Tx mitigates macrophage-driven inflammation.

Clinical significance

Tx may enhance bone regeneration by modulating inflammatory responses and preserving cell integrity.

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来源期刊

Journal of dentistry 医学-牙科与口腔外科

CiteScore

7.30

自引率

11.40%

发文量

349

审稿时长

35 days

期刊介绍： The Journal of Dentistry has an open access mirror journal The Journal of Dentistry: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. The Journal of Dentistry is the leading international dental journal within the field of Restorative Dentistry. Placing an emphasis on publishing novel and high-quality research papers, the Journal aims to influence the practice of dentistry at clinician, research, industry and policy-maker level on an international basis. Topics covered include the management of dental disease, periodontology, endodontology, operative dentistry, fixed and removable prosthodontics, dental biomaterials science, long-term clinical trials including epidemiology and oral health, technology transfer of new scientific instrumentation or procedures, as well as clinically relevant oral biology and translational research. The Journal of Dentistry will publish original scientific research papers including short communications. It is also interested in publishing review articles and leaders in themed areas which will be linked to new scientific research. Conference proceedings are also welcome and expressions of interest should be communicated to the Editor.