Abstract：
Resorption and atrophy of the alveolar bone, as two consequences of osteoporosis that remarkably complicate the orthodontic and prosthodontic treatments, contribute to the differentiated biological features and force-induced response of jaw bone marrow-derived mesenchymal stem cells (JBMSCs) in elderly patients. We isolated and cultured JBMSCs from adolescent and adult patients and then simulated the loading of orthodontic tension stress by constructing an in vitro three-dimensional (3D) stress loading model. The decline in osteogenic differentiation of aged JBMSCs was reversed by tensile stress stimulation. It is interesting to note that tension stimulation had a stronger effect on the osteogenic differentiation of elderly JBMSCs compared to the young ones, indicating a possible mechanism of aging rescue. High-throughput sequencing of microRNA (miRNAs) was subsequently performed before and after tension stimulation in all JBMSCs, followed by the comprehensive comparison of mechanically responsive miRNAs in the 3D strain microenvironment. The results suggested a significant reduction in the expression of miR-210-3p and miR-214-3p triggered by the 3D strain microenvironment in old-JBMSCs. Bioinformatic analysis indicated that both miRNAs participate in the regulation of critical pathways of aging and cellular senescence. Taken together, this study demonstrated that the 3D strain microenvironment efficiently rescued the cellular senescence of old-JBMSCs via modulating specific miRNAs, which provides a novel strategy for coordinating periodontal bone loss and regeneration of the elderly.
摘要：
牙槽骨的吸收和萎缩，作为骨质疏松症的两个后果，显着复杂的正畸和修复治疗，促进老年患者颌骨骨髓间充质干细胞(JBMSCs)的分化生物学特性及力诱导反应。我们从青少年和成年患者中分离和培养JBMSCs，然后通过构建体外三维（3D）应力加载模型来模拟正畸张应力的加载。拉伸应力刺激逆转了老年JBMSCs成骨分化的下降。值得注意的是，与年轻的JBMSCs相比，张力刺激对老年JBMSCs的成骨分化具有更强的影响，表明衰老救援的可能机制。随后在所有JBMSCs的张力刺激前后进行微小RNA（miRNA）的高通量测序，其次是3D菌株微环境中机械响应miRNAs的综合比较。结果表明，3D菌株微环境在旧JBMSCs中引起的miR-210-3p和miR-214-3p的表达显着降低。生物信息学分析表明，两种miRNA都参与衰老和细胞衰老的关键途径的调节。一起来看,这项研究表明，3D菌株微环境通过调节特定的miRNAs有效地拯救了老年JBMSCs的细胞衰老，为协调老年人牙周骨丢失和再生提供了新的策略。
