Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit.

IF 8 2区生物学 Q1 BIOLOGY

Science China Life Sciences Pub Date : 2025-04-01 Epub Date: 2025-01-13 DOI:10.1007/s11427-024-2745-2

Ruyu Wang, Tianxiao Wang, Ziyu Chen, Jiandong Jiang, Yifei Du, Hua Yuan, Yongchu Pan, Yuli Wang

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引用次数: 0

Abstract

Delayed tooth extraction socket (TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils (ANs), and neutrophil extracellular traps (NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium (CM) collected from berberine-treated human bone marrow mesenchymal stem cells (BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

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小檗碱处理的人骨髓间充质干细胞的生物活性物质通过颌骨血管单元加速拔牙槽愈合。

拔牙槽区（TES）愈合延迟会导致后续种植失败，增加患者的社会经济负担。过量的M1巨噬细胞、凋亡中性粒细胞（ANs）和中性粒细胞细胞外陷阱（NETs）会损害TES愈合过程中的牙槽骨再生。在本研究中，我们首次发现从小檗碱处理的人骨髓间充质干细胞（BBR-HB-CM）中收集的条件培养基（CM）加速TES愈合。BBR-HB-CM所含的生物活性物质能促进巨噬细胞从M1向M2极化，阻碍ANs和NETs的形成，并在体内外调节M2巨噬细胞的efferocysis。从机制上讲，BBR-HB-CM通过p85/AKT/mTOR途径依赖的自噬抑制巨噬细胞-肌成纤维细胞转化和巨噬细胞极化重编程，从而促进骨形成。3-甲基腺嘌呤消除了BBR-HB-CM的治疗效果。进一步研究表明，BBR-HB-CM可加速2型糖尿病大鼠TES愈合。总体而言，我们的结果表明，BBR-HB-CM具有促进TES快速愈合的高潜力。

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来源期刊

Science China Life Sciences BIOLOGY-

CiteScore

15.10

自引率

8.80%

发文量

2907

审稿时长

3.2 months

期刊介绍： Science China Life Sciences is a scholarly journal co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China, and it is published by Science China Press. The journal is dedicated to publishing high-quality, original research findings in both basic and applied life science research.