Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China.
Department of Stomatology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Stem Cell Res Ther. 2019 Aug 7;10(1):243. doi: 10.1186/s13287-019-1324-8.
The balance of oral microbiomes is crucial to maintain oral health. Microecological imbalance can impair the function of mesenchymal stem cells (MSCs) and lead to delay wound healing. Probiotics is a promising prevention approach for the treatment of oral inflammatory diseases caused by a bacterial infection. However, the effect of probiotics on oral MSCs and wound healing is unclear. In the present study, we used one type of probiotics Lactobacillus reuteri extracts to determine whether bacterial extracts could regulate the functions of gingiva MSCs (GMSCs) and promote wound healing.
Lactobacillus reuteri was prepared with bacterial extracts using ultrasonic crushing apparatus. The effects of Lactobacillus reuteri extracts on GMSCs were tested using the cell scratch migration, alkaline phosphatase (ALP) activity, alizarin red staining, cell counting kit-8, real-time PCR, and western blot assays. To investigate the role of Lactobacillus reuteri extracts in the wound in mice, the wound position of bilateral mesial gingival of the maxillary first molar was established, the wound area with a size of 1 mm × 2 mm and the full thickness gingiva was removed. Mice with wound were randomly distributed to two groups: injection of 0.9% NaCl (NS group) or injection of 50 μg/ml bacterial extracts.
We discovered that 50 μg/ml Lactobacillus reuteri extracts increased the capacities of migration, expression of stem cell markers, osteogenic differentiation, and proliferation of GMSCs. In addition, local injection of 50 μg/ml bacterial extracts could promote wound-healing process in mice models. Mechanistically, we found that Lactobacillus reuteri extracts accelerated the process of wound healing via PI3K/AKT/β-catenin/TGFβ1 pathway.
These data showed that Lactobacillus reuteri extracts could activate the potentials of GMSCs, thus promote wound healing. Our discovery provided the insight of the underlying mechanism activating functions of MSCs and identified Lactobacillus reuteri extracts as a potential therapeutic strategy for accelerating oral wound and potential application in the future dental clinic.
口腔微生物组的平衡对于维持口腔健康至关重要。微生物生态失衡会损害间充质干细胞（MSCs）的功能，导致伤口愈合延迟。益生菌是治疗细菌感染引起的口腔炎症性疾病的一种有前途的预防方法。然而，益生菌对口腔 MSCs 和伤口愈合的影响尚不清楚。在本研究中，我们使用一种益生菌乳杆菌提取物来确定细菌提取物是否可以调节牙龈间充质干细胞（GMSCs）的功能并促进伤口愈合。
使用超声破碎仪制备乳杆菌提取物。通过细胞划痕迁移、碱性磷酸酶（ALP）活性、茜素红染色、细胞计数试剂盒-8、实时 PCR 和 Western blot 检测乳杆菌提取物对 GMSCs 的影响。为了研究乳杆菌提取物在小鼠伤口中的作用，建立上颌第一磨牙双侧近中牙龈的伤口位置，去除大小为 1mm×2mm 和全厚牙龈的伤口。将有伤口的小鼠随机分为两组：注射 0.9%NaCl（NS 组）或注射 50μg/ml 细菌提取物。
我们发现 50μg/ml 乳杆菌提取物增加了 GMSCs 的迁移能力、干细胞标志物表达、成骨分化和增殖能力。此外，局部注射 50μg/ml 细菌提取物可促进小鼠模型的伤口愈合过程。在机制上，我们发现乳杆菌提取物通过 PI3K/AKT/β-catenin/TGFβ1 途径加速了伤口愈合过程。
这些数据表明，乳杆菌提取物可以激活 GMSCs 的潜力，从而促进伤口愈合。我们的发现提供了激活 MSCs 功能的潜在机制的见解，并确定了乳杆菌提取物作为加速口腔伤口愈合的潜在治疗策略，并有潜力在未来的牙科临床中应用。
