School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, 211166, China; Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China; Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing, 210029, China; Department of Stomatology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, China.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China; Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing, 210029, China.
Biochem Biophys Res Commun. 2020 Oct 15;531(2):228-235. doi: 10.1016/j.bbrc.2020.06.146. Epub 2020 Aug 13.
Osteoporosis is a common bone disorder with adverse effects on oral osseointegration, and the effects of metformin on bone metabolism have received increasing attention. The aim of the present study was to test the hypothesis that metformin promoted osteogenesis of bone mesenchymal stem cells (BMSCs) and osseointegration of titanium implants. BMSCs were treated with metformin to assess autophagic capacity, reactive oxygen species (ROS) production, anti-aging ability, and osteogenic differentiation. To determine its potential application in peri-implant of the maxilla, metformin was injected around the implant each day, immediately after the implant was embedded into the tooth socket. The results showed that metformin increased the autophagic capacity and decreased ROS production of osteoporotic BMSCs under hypoxia and serum deprivation (H/SD) culturing conditions. Metformin treatment significantly enhanced stemness properties and mineralized nodule formation, and increased the expression of osteogenic markers, including runt related transcription factor 2 (Runx2), osteocalcin (OCN), and alkaline phosphatase (ALP). Moreover, metformin substantially accelerated the formation of new bone, ameliorated the bone microarchitecture and promoted osseointegration of the dental implant. Collectively, metformin induces an osteogenic effect around the implant. Considering the widespread use of metformin, the results of the present study might promote a novel understanding of the positive effects of local metformin delivery on alveolar ridge defect, and have potential clinical application for the acceleration of osseointegration.
骨质疏松症是一种常见的骨骼疾病，对口腔骨整合有不良影响，二甲双胍对骨骼代谢的影响受到越来越多的关注。本研究旨在检验二甲双胍促进骨髓间充质干细胞（BMSCs）成骨和钛种植体骨整合的假说。用二甲双胍处理 BMSCs 以评估自噬能力、活性氧（ROS）产生、抗衰老能力和成骨分化。为了确定其在颌骨种植体周围的潜在应用，在将种植体嵌入牙槽窝后，每天在种植体周围注射二甲双胍。结果表明，二甲双胍在缺氧和血清剥夺（H/SD）培养条件下增加了骨质疏松症 BMSCs 的自噬能力并减少了 ROS 的产生。二甲双胍处理显著增强了干细胞特性和矿化结节形成，并增加了成骨标志物的表达，包括 runt 相关转录因子 2（Runx2）、骨钙素（OCN）和碱性磷酸酶（ALP）。此外，二甲双胍还大大加速了新骨的形成，改善了骨微结构，并促进了牙种植体的骨整合。总之，二甲双胍在种植体周围诱导成骨作用。鉴于二甲双胍的广泛应用，本研究结果可能促进对局部二甲双胍给药对牙槽嵴缺损的积极影响的新认识，并具有加速骨整合的潜在临床应用。
