Wang Zhao, Song Ju Han, Kim Jung-Woo, Kwon Seung-Hee, Piao Xianyu, Oh Sin-Hye, Park Suk-Gyun, Kim Sun-Hun, Ryu Je-Hwang, Kim Ok-Su, Koh Jeong-Tae
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
Hard-tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
J Periodontol. 2025 Apr 2. doi: 10.1002/JPER.24-0684.
Periodontitis is a destructive disease that affects periodontal tissue. While current research focuses on disease management, research on tissue repair remains limited. Metformin, a first-line medication for diabetes treatment, has positive effects on bone health in nondiabetic patients. However, its potential for repairing periodontal tissue remains unclear. Therefore, this study aimed to evaluate the reparative effects of metformin on periodontitis-damaged periodontal tissue in mice.
A mouse model of periodontal repair was used, in which silk ligatures were removed from the molars after inducing periodontitis, followed by metformin administration. Histomorphometric and histological analyses were conducted to assess comprehensive repair of the periodontium. Additional in vitro studies were conducted to determine the effect of metformin on the function of the individual cells that comprise the periodontium.
Metformin treatment promoted the repair of periodontal ligament, alveolar bone, and cementum affected by periodontitis, as evaluated using microcomputed tomography based morphometric and histologic analyses. The therapeutic effect was linked to mitigating persistent inflammatory activity during periodontitis resolution, primarily attributed to the sustained presence of interleukin-1 beta (IL-1β), which may delay tissue repair. In vitro studies simulating this pathological condition showed that AMP-activated protein kinase (AMPK) activation by metformin counteracted the effect of IL-1β, inhibited osteoclast differentiation and restored the osteogenic differentiation capacity of periodontal ligament cells and cementoblasts.
These findings suggest that metformin holds promise for repairing periodontal tissue following periodontitis, potentially through modulating inflammatory responses and regulating cellular differentiation processes.
Periodontitis is a serious gum disease that destroys the structures that support the teeth, such as ligaments and bone. While current treatments focus on preventing further damage, little progress has been made in achieving complete restoration of damaged tissue. In this study, we investigated whether metformin, a common diabetes drug, could help repair periodontal tissue. Using a mouse model of periodontitis, we removed ligatures placed around the teeth to allow healing, followed by metformin treatment. Our results showed that metformin promoted the repair of key tissues such as the periodontal ligament, alveolar bone, and cementum. An important observation in this study is the persistence of inflammatory activity during periodontitis resolution, where prolonged inflammation, driven by molecules such as interleukin-1β (IL-1β), appears to hinder tissue recovery. Metformin was found to counteract prolonged inflammation by reducing IL-1β activity, allowing tissue to heal. It also restored the function of bone-forming cells and limited the activity of bone-resorbing cells. These results suggest that metformin may be a promising therapy for promoting periodontal tissue repair by both controlling inflammation and enhancing cellular activity critical for tissue restoration.
牙周炎是一种影响牙周组织的破坏性疾病。虽然目前的研究集中在疾病管理方面，但关于组织修复的研究仍然有限。二甲双胍是治疗糖尿病的一线药物，对非糖尿病患者的骨骼健康有积极作用。然而，其修复牙周组织的潜力仍不明确。因此，本研究旨在评估二甲双胍对小鼠牙周炎损伤的牙周组织的修复作用。
采用小鼠牙周修复模型，在诱导牙周炎后从磨牙上移除丝线结扎，随后给予二甲双胍。进行组织形态计量学和组织学分析以评估牙周组织的全面修复。还进行了额外的体外研究，以确定二甲双胍对构成牙周组织的单个细胞功能的影响。
使用基于微型计算机断层扫描的形态计量学和组织学分析评估，二甲双胍治疗促进了受牙周炎影响的牙周韧带、牙槽骨和牙骨质的修复。治疗效果与减轻牙周炎消退过程中持续的炎症活动有关，主要归因于白细胞介素-1β（IL-1β）的持续存在，这可能会延迟组织修复。模拟这种病理状况的体外研究表明，二甲双胍激活的AMP活化蛋白激酶（AMPK）抵消了IL-1β的作用，抑制破骨细胞分化，并恢复了牙周韧带细胞和成牙骨质细胞的成骨分化能力。
这些发现表明，二甲双胍有望修复牙周炎后的牙周组织，可能是通过调节炎症反应和调节细胞分化过程来实现。
牙周炎是一种严重的牙龈疾病，会破坏支撑牙齿的结构，如韧带和骨骼。虽然目前的治疗重点是防止进一步损伤，但在实现受损组织的完全恢复方面进展甚微。在这项研究中，我们调查了常用的糖尿病药物二甲双胍是否有助于修复牙周组织。我们使用牙周炎小鼠模型，移除牙齿周围放置的结扎线以促进愈合，随后进行二甲双胍治疗。我们的结果表明，二甲双胍促进了牙周韧带、牙槽骨和牙骨质等关键组织的修复。本研究中的一个重要观察结果是，在牙周炎消退过程中炎症活动持续存在，由白细胞介素-1β（IL-1β）等分子驱动的长期炎症似乎会阻碍组织恢复。发现二甲双胍通过降低IL-1β活性来对抗长期炎症，使组织得以愈合。它还恢复了成骨细胞的功能并限制了破骨细胞的活性。这些结果表明，二甲双胍可能是一种有前景的治疗方法，通过控制炎症和增强对组织修复至关重要的细胞活性来促进牙周组织修复。
