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二甲双胍碳点通过激活 ERK/AMPK 通路促进牙周骨再生。

Metformin Carbon Dots for Promoting Periodontal Bone Regeneration via Activation of ERK/AMPK Pathway.

机构信息

Hospital of Stomatology, Jilin University, Changchun, 130021, P. R. China.

Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, P. R. China.

出版信息

Adv Healthc Mater. 2021 Jun;10(12):e2100196. doi: 10.1002/adhm.202100196. Epub 2021 May 14.

DOI:10.1002/adhm.202100196
PMID:33987977
Abstract

The osteogenic potential of mesenchymal stem cells (MSCs) is severely impaired under persistent inflammation of periodontitis. A highly efficient way to promote or rescue osteogenic potential of MSCs under inflammation remains an unmet goal. Herein, metformin carbon dots (MCDs) with excellent biocompatibility are prepared from metformin hydrochloride and citric acid via a hydrothermal method. The MCDs can more effectively enhance the alkaline phosphatase (ALP) activity, calcium deposition nodules formation, expression of osteogenic genes and proteins in rat bone marrow mesenchymal stem cells (rBMSCs) than metformin under both inflammatory and normal conditions. Moreover, a novel pathway of extracellular signal-regulated kinases (ERK)/AMP-activated protein kinase (AMPK) signaling is involved in the MCDs-induced osteogenesis. In periodontitis rats, MCDs can effectively regenerate the lost alveolar bone, but not the metformin. Taken together, MCDs can be the promising candidate nanomaterial for periodontitis treatment. This work may provide a new pharmacological target of ERK/AMPK pathway for treating bone loss and also give additional insights into developing nanodrugs from the numerous medications.

摘要

成骨细胞的间充质干细胞 (MSCs) 的潜力是严重受损的牙周炎的持续炎症。一种有效的方法来促进或挽救成骨细胞的间充质干细胞在炎症下仍然是一个未满足的目标。在此,二甲双胍碳点 (MCDs) 具有良好的生物相容性从盐酸二甲双胍和柠檬酸通过水热法。MCDs 能更有效地增强碱性磷酸酶 (ALP) 活性,钙沉积结节形成,表达成骨基因和蛋白质大鼠骨髓间充质干细胞 (rBMSCs) 比二甲双胍在炎症和正常条件下。此外,细胞外信号调节激酶 (ERK)/AMP 激活蛋白激酶 (AMPK) 信号转导的新途径参与 MCDs 诱导的成骨作用。在牙周炎大鼠中,MCDs 能有效地再生失去的牙槽骨,但不是二甲双胍。总之,MCDs 可以成为治疗牙周炎的有前途的纳米材料候选物。这项工作可能为治疗骨丢失的 ERK/AMPK 通路提供新的药理学靶点,也为从众多药物中开发纳米药物提供了更多的见解。

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