Toledano Raquel, Osorio María T, Osorio Raquel, Toledano Manuel, Jacho Diego, Yildirim-Ayan Eda
Dental School, University of Granada, Colegio Máximo de Cartuja, Granada, Spain.
Bioengineering Department, University of Toledo, Toledo, Ohio, USA.
J Dent. 2025 Feb;153:105509. doi: 10.1016/j.jdent.2024.105509. Epub 2024 Dec 5.
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.
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.
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.
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.
Tx may enhance bone regeneration by modulating inflammatory responses and preserving cell integrity.
替格列净（Tx）以其成骨潜能而闻名，但其对成骨细胞与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并评估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作用及联合作用，特别关注在有或没有Tx的情况下这些相互作用如何影响成骨和破骨细胞生成的蛋白质表达。
将成骨细胞和巨噬细胞直接接触共培养24小时和48小时，有或没有Tx存在。进行碱性磷酸酶活性检测、使用RT-qPCR检测炎症相关基因的表达以及组织学分析。
将成骨细胞和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处理有助于维持支架内细胞形态的稳定性，表明为细胞活力和功能提供了支持性环境。Tx在24小时和48小时均显著降低了共培养物中促炎标志物如TNF-α和IL-1β的表达。Tx还有效抑制了巨噬细胞中的破骨细胞分化，从而减轻了它们的促炎表型。
Tx增加了碱性磷酸酶活性并显著上调了RANKL表达，表明成骨细胞分化和破骨细胞活化增强。Tx减轻了巨噬细胞驱动的炎症。
Tx可能通过调节炎症反应和维持细胞完整性来促进骨再生。
